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Diker Cohen T, Rudman Y, Turjeman A, Akirov A, Steinmetz T, Calvarysky B, Dotan I. Glucagon-like peptide 1 receptor agonists and renal outcomes in kidney transplant recipients with diabetes mellitus. DIABETES & METABOLISM 2025; 51:101624. [PMID: 39961479 DOI: 10.1016/j.diabet.2025.101624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 02/06/2025] [Accepted: 02/08/2025] [Indexed: 02/23/2025]
Abstract
AIMS Glucagon-like peptide-1 receptor agonists (GLP1-RAs) show reno-protective effects in type 2 diabetes. Limited data is available on their use in post-transplant diabetes mellitus. We aimed to explore the effect of GLP1-RAs on renal outcomes in diabetic kidney transplant recipients (KTR). METHODS We conducted a cohort retrospective study on adult KTR with diabetes mellitus. KTR treated with GLP1-RAs were matched with non-users. The primary outcome was the first occurrence of graft rejection, start of dialysis, re-transplantation or all-cause mortality. Other outcomes included a composite of the first occurrence of a genitourinary infection or all-cause mortality, and all-cause mortality. Metabolic effects of GLP1-RA treatment and risk for biliopancreatic adverse events were also explored. RESULTS We included 272 patients (69 % males, average age 58.3 ± 11.0 years) with a 3.1-year median follow-up. The use of GLP1-RAs lowered the incidence of the composite renal outcome after adjustment for independent risk factors (114 versus 68 events per 1000-patient years in controls versus GLP1-RA users, HR 0.489, 95 % CI 0.271-0.883). GLP-RA users had improved glycemic control, lipid profile and a decrease in body mass index. The treatment was safe without increased genitourinary infections or biliopancreatic events. CONCLUSION The use of GLP1-RAs decreased the risk of a composite outcome of renal dysfunction and mortality, improved metabolic control and showed safety of use in a large cohort of diabetic KTR, suggesting reno-protective effects in this high-risk population. Prospective data is further needed in KTR who are excluded from large RCTs.
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Affiliation(s)
- Talia Diker Cohen
- Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Yaron Rudman
- Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Adi Turjeman
- Research authority, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Amit Akirov
- Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tali Steinmetz
- Institute of Nephrology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Bronya Calvarysky
- Pharmacy, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Idit Dotan
- Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Lin LC, Chen JY, Huang TTM, Wu VC. Association of glucagon-like peptide-1 receptor agonists with cardiovascular and kidney outcomes in type 2 diabetic kidney transplant recipients. Cardiovasc Diabetol 2025; 24:87. [PMID: 39984953 PMCID: PMC11846168 DOI: 10.1186/s12933-025-02649-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 02/13/2025] [Indexed: 02/23/2025] Open
Abstract
BACKGROUND Cardiovascular disease is a leading cause of post-transplant mortality in kidney transplant recipients (KTRs), especially those with diabetes. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and kidney benefits in the general population with type 2 diabetes mellitus (T2DM), evidence regarding their effects in diabetic KTRs is limited. METHODS This retrospective cohort study utilized data from the Global Collaborative Network in TriNetX, spanning January 1, 2006, to June 1, 2023. Propensity score matching (PSM) with 1:1 ratio was employed to create balanced cohorts. Adult KTRs with T2DM who received GLP-1 RAs within 3 months post-transplant were compared to a matched cohort of KTRs who did not. The primary outcome was all-cause mortality, with secondary outcomes including major adverse cardiovascular events (MACEs) and major adverse kidney events (MAKEs). RESULTS A total of 35,488 adult KTRs with T2DM (mean [SD] age, 57.7 [12.2] years; 57.7% men) were identified and 9.8% patients used GLP-1 RAs among 3 months post-transplant. Following PSM, 3564 GLP-1 RAs users were matched with an equal number of nonusers. After a median follow-up of 2.5 years, GLP-1 RAs users had lower risks of mortality (adjusted hazard ratio (aHR), 0.39; 95% CI 0.31-0.50), MACEs (aHR 0.66; 95% CI 0.56-0.79), and MAKEs (aHR 0.66; 95% CI 0.58-0.75). Adverse effects included higher risks of nausea, vomiting and diarrhea, while risks of suicide, hypoglycemia, retinopathy, and pancreatitis were not increased. CONCLUSIONS In KTRs with T2DM, GLP-1 RAs use was associated with substantial reductions in all-cause mortality, MAKEs, and MACEs compared to nonuse without increasing complications. However, the underutilization of GLP-1 RAs represents a significant opportunity to improve post-transplant outcomes in this high-risk population.
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Affiliation(s)
- Li-Chun Lin
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jui-Yi Chen
- Division of Nephrology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
- Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Thomas Tao-Min Huang
- Division of Nephrology, Primary Aldosteronism Center of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- NSARF (National Taiwan University Hospital Study Group of ARF), and CAKS (Taiwan Consortium for Acute Kidney Injury and Renal Diseases), Taipei, Taiwan
| | - Vin-Cent Wu
- Division of Nephrology, Primary Aldosteronism Center of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- NSARF (National Taiwan University Hospital Study Group of ARF), and CAKS (Taiwan Consortium for Acute Kidney Injury and Renal Diseases), Taipei, Taiwan.
- Department of Internal Medicine, National Taiwan University Hospital, Room 1555, B4, Clinical Research Building, 7 Chung-Shan South Road, Taipei, 100, Taiwan.
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Cigrovski Berkovic M, Šeša V, Balen I, Lai Q, Silovski H, Mrzljak A. Key challenges of post-liver transplant weight management. World J Transplant 2024; 14:95033. [PMID: 39697459 PMCID: PMC11438933 DOI: 10.5500/wjt.v14.i4.95033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 08/21/2024] [Accepted: 09/09/2024] [Indexed: 09/20/2024] Open
Abstract
Liver transplantation serves as a life-saving intervention for patients with end-stage liver disease, yet long-term survival remains a challenge. Post-liver transplant obesity seems to have a significant contribution to this challenge and it emerges as a significant risk factor for graft steatosis, metabolic syndrome and de-novo malignancy development. This review synthesizes current literature on prevalence, risk factors and management strategies for post-liver transplant obesity, emphasizing its impact on graft and patient survival. Literature review consultation was conducted in Medline/PubMed, SciELO and EMBASE, with the combination of the following keywords: Weight management, liver transplantation, immunosuppressive therapy, lifestyle interventions, bariatric surgery. Immunosuppressive therapy has a significant influence on long-term survival of liver transplant patients, yet it seems to have lesser effect on post-transplant obesity development than previously thought. However, it significantly contributes to the development of other components of metabolic syndrome. Key predisposing factors for post-transplant obesity development encompass elevated recipient and donor body mass index, a history of alcoholic liver disease, hepatocellular carcinoma, male gender, the absence of cellular rejection and the marital status of the recipient. Tailored immunosuppressive regimens, pharmacotherapy, lifestyle interventions and bariatric surgery represent key components in mitigating post-transplant obesity and improving long-term survival and quality of life in this group of patients. Timely identification and intervention thus hold paramount importance. Further research is warranted to refine optimal management strategies and enhance outcomes in this patient population.
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Affiliation(s)
- Maja Cigrovski Berkovic
- Department for Sport and Exercise Medicine, University of Zagreb, Faculty of Kinesiology, Zagreb 10000, Croatia
| | - Vibor Šeša
- Department of Gastroenterology and Hepatology, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Ivan Balen
- Department of Gastroenterology and Endocrinology, General Hospital “Dr. Josip Bencevic”, Slavonski Brod 35000, Croatia
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, Rome 00018, Italy
| | - Hrvoje Silovski
- Department of Hepatobiliary Surgery and Transplantation, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Centre Zagreb, Zagreb 10000, Croatia
- Department of Medicine, University of Zagreb, School of Medicine, Zagreb 10000, Croatia
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Riehl-Tonn VJ, Medak KD, Rampersad C, MacPhee A, Harrison TG. GLP-1 Agonism for Kidney Transplant Recipients: A Narrative Review of Current Evidence and Future Directions Across the Research Spectrum. Can J Kidney Health Dis 2024; 11:20543581241290317. [PMID: 39492845 PMCID: PMC11528610 DOI: 10.1177/20543581241290317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 08/25/2024] [Indexed: 11/05/2024] Open
Abstract
Purpose of Review Diabetes is the most common cause of kidney disease in individuals that receive a kidney transplant, and those without pre-existing diabetes are at greater risk of developing diabetes following kidney transplant. A class of diabetes treatment medications called glucagon-like peptide-1 receptor agonists (GLP-1RA) has seen recent widespread use for people with diabetes or obesity, with efficacy for improved glycemic control, weight loss, and reduced risk of cardiovascular events. Given these benefits, and indications for use that often co-occur in kidney transplant recipients, use of GLP-1RAs warrants consideration in this population. Therefore, we sought to review the current literature to better understand the mechanisms of action, clinical application, and person-centred considerations of GLP-1RAs in kidney transplant recipients. Sources of Information Original articles were identified between December 2023 and July 2024 from electronic databases including the Ovid MEDLINE database, PubMed, and Google Scholar using terms "kidney transplant," "GLP-1," "glucagon-like peptide-1 receptor agonist," and "diabetes." Methods A comprehensive review of the literature was conducted to explore the relationship between GLP-1RAs and kidney transplant recipients. We reviewed the current state of evidence across the research disciplines of basic or fundamental science, clinical and health services research, and person-centred equity science, and highlighted important knowledge gaps that offer opportunities for future research. Key Findings Numerous clinical studies have demonstrated the benefit of GLP-1RAs in people with and without diabetic kidney disease, including decreased risk of cardiovascular events. However, there is a paucity of high-quality randomized controlled trials and observational studies analyzing use of GLP-1RAs in kidney transplant recipients. Evidence of benefit in this population is therefore limited to small studies or inferred from research conducted in nontransplant populations. Growing evidence from preclinical and clinical studies may elucidate renoprotective mechanisms of GLP-1RAs and remove barriers to application of these drugs in the transplant recipient population. Individuals who are female, non-white, have lower socioeconomic status, and live in rural communities are at greater risk of diabetes and have lower uptake of GLP-1RAs. There is a need for clinical trials across diverse kidney transplant populations to estimate the efficacy of GLP-1RAs on important health outcomes. Limitations The search strategy for this narrative review may not have been sensitive to identify all relevant articles. Our search was limited to English language articles.
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Affiliation(s)
- Victoria J. Riehl-Tonn
- Department of Medicine, University of Calgary, AB, Canada
- Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, AB, Canada
| | - Kyle D. Medak
- Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada
| | - Christie Rampersad
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, ON, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, ON, Canada
| | - Anne MacPhee
- Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD), Vancouver, BC, Canada
| | - Tyrone G. Harrison
- Department of Medicine, University of Calgary, AB, Canada
- Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, AB, Canada
- Department of Community Health Sciences, University of Calgary, AB, Canada
- O’Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, AB, Canada
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Rudzki G, Knop-Chodyła K, Piasecka Z, Kochanowska-Mazurek A, Głaz A, Wesołek-Bielaska E, Woźniak M. Managing Post-Transplant Diabetes Mellitus after Kidney Transplantation: Challenges and Advances in Treatment. Pharmaceuticals (Basel) 2024; 17:987. [PMID: 39204092 PMCID: PMC11357592 DOI: 10.3390/ph17080987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/10/2024] [Accepted: 07/16/2024] [Indexed: 09/03/2024] Open
Abstract
Kidney transplantation is the most effective treatment for end-stage renal failure but is associated with complications, including post-transplant diabetes mellitus (PTDM). It affects the quality of life and survival of patients and the transplanted organ. It can cause complications, including infections and episodes of acute rejection, further threatening graft survival. The prevalence of PTDM, depending on the source, can range from 4 to 30% in transplant patients. This article aims to discuss issues related to diabetes in kidney transplant patients and the latest treatments. Knowledge of the mechanisms of action of immunosuppressive drugs used after transplantation and their effect on carbohydrate metabolism is key to the rapid and effective detection of PTDM. Patient therapy should not only include standard management such as lifestyle modification, insulin therapy or pharmacotherapy based on well-known oral and injection drugs. New opportunities are offered by hypoglycemic drugs still in clinical trials, including glucokinase activators, such as dorzagliatin, ADV-1002401, LY2608204, TMG-123, imeglimine, amycretin and pramlintide. Although many therapeutic options are currently available, PTDM often creates uncertainty about the most appropriate treatment strategy. Therefore, more research is needed to individualize therapeutic plans and monitor these patients.
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Affiliation(s)
- Grzegorz Rudzki
- Department of Endocrinology, Diabetology and Metabolic Diseases, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
| | - Kinga Knop-Chodyła
- University Clinical Hospital No. 4 in Lublin, Jaczewskiego 8, 20-954 Lublin, Poland; (K.K.-C.); (E.W.-B.)
| | - Zuzanna Piasecka
- Saint Queen Jadwiga’s Regional Clinical Hospital No. 2 in Rzeszow, Lwowska 60, 35-301 Rzeszów, Poland;
| | - Anna Kochanowska-Mazurek
- Stefan Cardinal Wyszynski Province Specialist Hospital, al. Kraśnicka 100, 20-718 Lublin, Poland;
| | - Aneta Głaz
- Faculty of medicine, Medical University of Lublin, al. Racławickie 1, 20-059 Lublin, Poland;
| | - Ewelina Wesołek-Bielaska
- University Clinical Hospital No. 4 in Lublin, Jaczewskiego 8, 20-954 Lublin, Poland; (K.K.-C.); (E.W.-B.)
| | - Magdalena Woźniak
- Department of Endocrinology, Diabetology and Metabolic Diseases, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
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Bellanca CM, Augello E, Di Benedetto G, Burgaletto C, Cantone AF, Cantarella G, Bernardini R, Polosa R. A web-based scoping review assessing the influence of smoking and smoking cessation on antidiabetic drug meabolism: implications for medication efficacy. Front Pharmacol 2024; 15:1406860. [PMID: 38957391 PMCID: PMC11217182 DOI: 10.3389/fphar.2024.1406860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 05/20/2024] [Indexed: 07/04/2024] Open
Abstract
Currently 1.3 billion individuals globally engage in smoking, leading to significant morbidity and mortality, particularly among diabetic patients. There is urgent need for a better understanding of how smoking influences antidiabetic treatment efficacy. The review underscores the role of cigarette smoke, particularly polycyclic aromatic hydrocarbons (PAHs), in modulating the metabolic pathways of antidiabetic drugs, primarily through the induction of cytochrome P450 (CYP450) enzymes and uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), thus impacting drug pharmacokinetics and therapeutic outcomes. Furthermore, the review addresses the relatively uncharted territory of how smoking cessation influences diabetes treatment, noting that cessation can lead to significant changes in drug metabolism, necessitating dosage adjustments. Special attention is given to the interaction between smoking cessation aids and antidiabetic medications, a critical area for patient safety and effective diabetes management. This scoping review aims to provide healthcare professionals with the knowledge to better support diabetic patients who smoke or are attempting to quit, ensuring tailored and effective treatment strategies. It also identifies gaps in current research, advocating for more studies to fill these voids, thereby enhancing patient care and treatment outcomes for this at-risk population.
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Affiliation(s)
- Carlo Maria Bellanca
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy
- Clinical Toxicology Unit, University Hospital of Catania, Catania, Italy
| | - Egle Augello
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy
- Clinical Toxicology Unit, University Hospital of Catania, Catania, Italy
| | - Giulia Di Benedetto
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy
- Clinical Toxicology Unit, University Hospital of Catania, Catania, Italy
| | - Chiara Burgaletto
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy
| | - Anna Flavia Cantone
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy
| | - Giuseppina Cantarella
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy
| | - Renato Bernardini
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy
- Clinical Toxicology Unit, University Hospital of Catania, Catania, Italy
| | - Riccardo Polosa
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
- Centre of Excellence for the Acceleration of HArm Reduction (CoEHAR), University of Catania, Catania, Italy
- Centre for the Prevention and Treatment of Tobacco Addiction (CPCT), University Hospital of Catania, Catania, Italy
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Calvarysky B, Dotan I, Shepshelovich D, Leader A, Cohen TD. Drug-Drug Interactions Between Glucagon-Like Peptide 1 Receptor Agonists and Oral Medications: A Systematic Review. Drug Saf 2024; 47:439-451. [PMID: 38273155 PMCID: PMC11018670 DOI: 10.1007/s40264-023-01392-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2023] [Indexed: 01/27/2024]
Abstract
BACKGROUND Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug absorption, potentially affecting pharmacokinetics, particularly in the case of medications with a narrow therapeutic index. PURPOSE The purpose of this systematic review is to summarize data on drug-drug interactions between GLP1RAs and oral drugs. DATA SOURCES The PubMed and EMBASE databases were searched up to November, 1st 2023. STUDY SELECTION We selected pharmacokinetic studies of any injectable GLP1RA given with an oral medication, and product prescribing sheets reporting data without access to the original study. DATA EXTRACTION Two authors independently extracted the data. DATA SYNTHESIS Twenty-two reports and six prescribing sheets were included. Treatment with GLP1RAs resulted in unaffected or reduced Cmax and delayed tmax of drugs with high solubility and permeability (warfarin, contraceptive pills, acetaminophen), drugs with high solubility and low permeability (angiotensin converting enzyme inhibitors), drugs with low solubility and high permeability (statins) and drugs with low solubility and permeability (digoxin). However, the use of GLP1RAs did not exert clinically significant changes in the AUC or differences in clinically relevant endpoints. LIMITATIONS The major limitations of the studies that are included in this systematic review are the enrollment of healthy subjects and insufficient data in conditions that might affect pharmacokinetics (e.g., kidney dysfunction). CONCLUSIONS To conclude, reduced Cmax and delayed tmax of drugs co-administered with GLP1RAs are consistent with the known delayed gastric output by the latter. Nevertheless, the overall drug exposure was not considered clinically significant. Dose adjustments are probably not required for simultaneous use of GLP1RAs with oral medications. Still, results should be carefully generalized to cases of background kidney dysfunction or when using drugs with narrow therapeutic index. The study is registered in PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332339 .
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Affiliation(s)
- Bronya Calvarysky
- Pharmacy, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Idit Dotan
- Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Daniel Shepshelovich
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
- Internal medicine D, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Avi Leader
- Institute of Hematology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Talia Diker Cohen
- Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Sharif A, Chakkera H, de Vries APJ, Eller K, Guthoff M, Haller MC, Hornum M, Nordheim E, Kautzky-Willer A, Krebs M, Kukla A, Kurnikowski A, Schwaiger E, Montero N, Pascual J, Jenssen TG, Porrini E, Hecking M. International consensus on post-transplantation diabetes mellitus. Nephrol Dial Transplant 2024; 39:531-549. [PMID: 38171510 PMCID: PMC11024828 DOI: 10.1093/ndt/gfad258] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Indexed: 01/05/2024] Open
Abstract
Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.
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Affiliation(s)
- Adnan Sharif
- Department of Nephrology and Transplantation, University Hospitals Birmingham, Birmingham, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Harini Chakkera
- Division of Nephrology and Hypertension, Mayo Clinic, Scottsdale, AZ, United States of America
| | - Aiko P J de Vries
- Leiden Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
- Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Kathrin Eller
- Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz Austria
| | - Martina Guthoff
- Department of Diabetology, Endocrinology, Nephrology, University of Tübingen, Tübingen, Germany
| | - Maria C Haller
- Ordensklinikum Linz, Elisabethinen Hospital, Department of Medicine III, Nephrology, Hypertension, Transplantation, Rheumatology, Geriatrics, Linz, Austria
- Medical University of Vienna, CeMSIIS, Section for Clinical Biometrics, Vienna, Austria
| | - Mads Hornum
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | - Espen Nordheim
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Nydalen, Norway
- Department of Nephrology, Oslo University Hospital-Ullevål, Oslo, Nydalen, Norway
| | - Alexandra Kautzky-Willer
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria
| | - Michael Krebs
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria
| | - Aleksandra Kukla
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States of America
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States of America
| | - Amelie Kurnikowski
- Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Elisabeth Schwaiger
- Department of Internal Medicine, Brothers of Saint John of God Eisenstadt, Eisenstadt, Austria
| | - Nuria Montero
- Nephrology Department, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, University of Barcelona, Barcelona Spain
| | - Julio Pascual
- Institute Mar for Medical Research-IMIM, Barcelona,Spain
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Trond G Jenssen
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Nydalen, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Esteban Porrini
- Instituto de Tecnologías Biomédicas (ITB), University of La Laguna, Research Unit Department, Hospital Universitario de Canarias, Tenerife, Spain
| | - Manfred Hecking
- Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
- Center for Public Health, Department of Epidemiology, Medical University of Vienna, Vienna, Austria
- Kuratorium for Dialysis and Kidney Transplantation (KfH), Neu-Isenburg, Germany
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Krisanapan P, Suppadungsuk S, Sanpawithayakul K, Thongprayoon C, Pattharanitima P, Tangpanithandee S, Mao MA, Miao J, Cheungpasitporn W. Safety and efficacy of glucagon-like peptide-1 receptor agonists among kidney transplant recipients: a systematic review and meta-analysis. Clin Kidney J 2024; 17:sfae018. [PMID: 38410684 PMCID: PMC10896177 DOI: 10.1093/ckj/sfae018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Indexed: 02/28/2024] Open
Abstract
Background Evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RAs) in kidney transplant recipients (KTRs) remains scarce. This systematic review and meta-analysis aims to evaluate the safety and efficacy of GLP-1RAs in this population. Methods A comprehensive literature search was conducted in the MEDLINE, Embase and Cochrane databases from inception through May 2023. Clinical trials and observational studies that reported on the safety or efficacy outcomes of GLP-1RAs in adult KTRs were included. Kidney graft function, glycaemic and metabolic parameters, weight, cardiovascular outcomes and adverse events were evaluated. Outcome measures used for analysis included pooled odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes and standardized mean difference (SMD) or mean difference (MD) with 95% CI for continuous outcomes. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023426190). Results Nine cohort studies with a total of 338 KTRs were included. The median follow-up was 12 months (interquartile range 6-23). While treatment with GLP-1RAs did not yield a significant change in estimated glomerular filtration rate [SMD -0.07 ml/min/1.73 m2 (95% CI -0.64-0.50)] or creatinine [SMD -0.08 mg/dl (95% CI -0.44-0.28)], they were associated with a significant decrease in urine protein:creatinine ratio [SMD -0.47 (95% CI -0.77 to -0.18)] and haemoglobin A1c levels [MD -0.85% (95% CI -1.41 to -0.28)]. Total daily insulin dose, weight and body mass index also decreased significantly. Tacrolimus levels remained stable [MD -0.43 ng/ml (95% CI -0.99 to 0.13)]. Side effects were primarily nausea and vomiting (17.6%), diarrhoea (7.6%) and injection site pain (5.4%). Conclusions GLP-1RAs are effective in reducing proteinuria, improving glycaemic control and supporting weight loss in KTRs, without altering tacrolimus levels. Gastrointestinal symptoms are the main side effects.
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Affiliation(s)
- Pajaree Krisanapan
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
- Division of Nephrology, Department of Internal Medicine, Thammasat University Hospital, Pathum Thani, Thailand
| | - Supawadee Suppadungsuk
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan Thailand
| | - Kanokporn Sanpawithayakul
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
- Department of Clinical Epidemiology, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Pattharawin Pattharanitima
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
| | - Supawit Tangpanithandee
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan Thailand
| | - Michael A Mao
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Jing Miao
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Wisit Cheungpasitporn
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA
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10
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Valencia-Morales ND, Rodríguez-Cubillo B, Loayza-López RK, Moreno de la Higuera MÁ, Sánchez-Fructuoso AI. Novel Drugs for the Management of Diabetes Kidney Transplant Patients: A Literature Review. Life (Basel) 2023; 13:1265. [PMID: 37374048 DOI: 10.3390/life13061265] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 05/18/2023] [Accepted: 05/22/2023] [Indexed: 06/29/2023] Open
Abstract
The management of diabetes and renal failure is changing thanks to the appearance of new drugs such as glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter type 2 inhibitors (SGLT2i) that have benefits in terms of survival and cardiorenal protection. Based on the potential mechanisms of GLP1-RA, kidney transplant recipients (KTRs) could benefit from their effects. However, high-quality studies are needed to demonstrate these benefits, in the transplant population, especially those related to cardiovascular benefits and renal protection. Studies with SGLT2i performed in KTRs are much less potent than in the general population and therefore no benefits in terms of patient or graft survival have been clearly demonstrated in this population to date. Additionally, the most frequently observed side effects could be potentially harmful to this population profile, including severe or recurrent urinary tract infections and impaired kidney function. However, benefits demonstrated in KTRs are in line with a known potential effects in cardiovascular and renal protection, which may be essential for the outcome of transplant recipients. Better studies are still needed to confirm the benefits of these new oral antidiabetics in the renal transplant population. Understanding the characteristics of these drugs may be critical for KTRs to be able to benefit from their effects without being damaged. This review discusses the results of the most important published studies on KTRs with GLP1-RA and SGLT2i as well as the potential beneficial effects of these drugs. Based on these results, approximate suggestions for the management of diabetes in KTRs were developed.
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11
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Sharif A. Interventions Against Posttransplantation Diabetes: A Scientific Rationale for Treatment Hierarchy Based on Literature Review. Transplantation 2022; 106:2301-2313. [PMID: 35696695 DOI: 10.1097/tp.0000000000004198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Posttransplant diabetes (PTD) is a common medical complication after solid organ transplantation. Because of adverse outcomes associated with its development and detrimental impact on long-term survival, strategies to prevent or manage PTD are critically important but remain underresearched. Treatment hierarchies of antidiabetic therapies in the general population are currently being revolutionized based on cardiovascular outcome trials, providing evidence-based rationale for optimization of medical management. However, opportunities for improving medical management of PTD are challenged by 2 important considerations: (1) translating clinical evidence data from the general population to underresearched solid organ transplant cohorts and (2) targeting treatment based on primary underlying PTD pathophysiology. In this article, the aim is to provide an overview of PTD treatment options from a new angle. Rationalized by a consideration of underlying PTD pathophysiological defects, which are heterogeneous among diverse transplant patient cohorts, a critical appraisal of the published literature and summary of current research in progress will be reviewed. The aim is to update transplant professionals regarding medical management of PTD from a new perspective tailored therapeutic intervention based on individualized characteristics. As the gap in clinical evidence between management of PTD versus type 2 diabetes widens, it is imperative for the transplant community to bridge this gap with targeted clinical trials to ensure we optimize outcomes for solid organ transplant recipients who are at risk or develop PTD. This necessary clinical research should help efforts to improve long-term outcomes for solid transplant patients from both a patient and graft survival perspective.
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Affiliation(s)
- Adnan Sharif
- Department of Nephrology and Transplantation, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.,Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
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12
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Newman JD, Schlendorf KH, Cox ZL, Zalawadiya SK, Powers AC, Niswender KD, Shah RV, Lindenfeld J. Post-transplant diabetes mellitus following heart transplantation. J Heart Lung Transplant 2022; 41:1537-1546. [DOI: 10.1016/j.healun.2022.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 06/22/2022] [Accepted: 07/13/2022] [Indexed: 10/31/2022] Open
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13
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Sridhar VS, Ambinathan JPN, Gillard P, Mathieu C, Cherney DZI, Lytvyn Y, Singh SK. Cardiometabolic and Kidney Protection in Kidney Transplant Recipients With Diabetes: Mechanisms, Clinical Applications, and Summary of Clinical Trials. Transplantation 2022; 106:734-748. [PMID: 34381005 DOI: 10.1097/tp.0000000000003919] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Kidney transplantation is the therapy of choice for patients with end-stage renal disease. Preexisting diabetes is highly prevalent in kidney transplant recipients (KTR), and the development of posttransplant diabetes is common because of a number of transplant-specific risk factors such as the use of diabetogenic immunosuppressive medications and posttransplant weight gain. The presence of pretransplant and posttransplant diabetes in KTR significantly and variably affect the risk of graft failure, cardiovascular disease (CVD), and death. Among the many available therapies for diabetes, there are little data to determine the glucose-lowering agent(s) of choice in KTR. Furthermore, despite the high burden of graft loss and CVD among KTR with diabetes, evidence for strategies offering cardiovascular and kidney protection is lacking. Recent accumulating evidence convincingly shows glucose-independent cardiorenal protective effects in non-KTR with glucose-lowering agents, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Therefore, our aim was to review cardiorenal protective strategies, including the evidence, mechanisms, and rationale for the use of these glucose-lowering agents in KTR with diabetes.
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Affiliation(s)
- Vikas S Sridhar
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- The Kidney Transplant Program and the Ajmera Tranplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Jaya Prakash N Ambinathan
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- The Kidney Transplant Program and the Ajmera Tranplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Pieter Gillard
- Department of Endocrinology, University Hospitals Leuven, Catholic University Leuven, Leuven, Belgium
| | - Chantal Mathieu
- Department of Endocrinology, University Hospitals Leuven, Catholic University Leuven, Leuven, Belgium
| | - David Z I Cherney
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Yuliya Lytvyn
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Sunita K Singh
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- The Kidney Transplant Program and the Ajmera Tranplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
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14
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Montero N, Oliveras L, Soler MJ, Cruzado JM. Management of post-transplant diabetes mellitus: an opportunity for novel therapeutics. Clin Kidney J 2022; 15:5-13. [PMID: 35265335 PMCID: PMC8901587 DOI: 10.1093/ckj/sfab131] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Indexed: 12/16/2022] Open
Abstract
Post-transplant diabetes mellitus (PTDM) is a common problem after kidney transplantation (KT), occurring in 50% of high-risk recipients. The clinical importance of PTDM lies in its impact as a significant risk factor for cardiovascular and chronic kidney disease (CKD) after solid organ transplantation. Kidney Disease: Improving Global Outcomes (KDIGO) has recently updated the treatment guidelines for diabetes management in CKD with emphasis on the newer antidiabetic agents such as dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors as add-on therapy to metformin. Given all these new diabetes treatments and the updated KDIGO guidelines, it is necessary to evaluate and give guidance on their use for DM management in KT recipients. This review summarizes the scarce published literature about the use of these new agents in the KT field. In summary, it is absolutely necessary to generate evidence in order to be able to safely use these new treatments in the KT population to improve blood glucose control, but specially to evaluate their potential cardiovascular and renal benefits that would seem to be independent of blood glucose control in PTDM patients.
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Affiliation(s)
- Nuria Montero
- Department of Nephrology, L'Hospitalet de Llobregat, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Laia Oliveras
- Department of Nephrology, L'Hospitalet de Llobregat, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Maria José Soler
- Department of Nephrology, Hospital Vall d'Hebron, Barcelona, Spain
| | - Josep Maria Cruzado
- Department of Nephrology, L'Hospitalet de Llobregat, Hospital Universitari de Bellvitge, Barcelona, Spain
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15
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Abstract
CONTEXT Though posttransplant diabetes mellitus (PTDM, occurring > 45 days after transplantation) and its complications are well described, early post-renal transplant hyperglycemia (EPTH) (< 45 days) similarly puts kidney transplant recipients at risk of infections, rehospitalizations, and graft failure and is not emphasized much in the literature. Proactive screening and management of EPTH is required given these consequences. OBJECTIVE The aim of this article is to promote recognition of early post-renal transplant hyperglycemia, and to summarize available information on its pathophysiology, adverse effects, and management. METHODS A PubMed search was conducted for "early post-renal transplant hyperglycemia," "immediate posttransplant hyperglycemia," "post-renal transplant diabetes," "renal transplant," "diabetes," and combinations of these terms. EPTH is associated with significant complications including acute graft failure, rehospitalizations, cardiovascular events, PTDM, and infections. CONCLUSION Patients with diabetes experience better glycemic control in end-stage renal disease (ESRD), with resurgence of hyperglycemia after kidney transplant. Patients with and without known diabetes are at risk of EPTH. Risk factors include elevated pretransplant fasting glucose, diabetes, glucocorticoids, chronic infections, and posttransplant infections. We find that EPTH increases risk of re-hospitalizations from infections (cytomegalovirus, possibly COVID-19), acute graft rejections, cardiovascular events, and PTDM. It is essential, therefore, to provide diabetes education to patients before discharge. Insulin remains the standard of care while inpatient. Close follow-up after discharge is recommended for insulin adjustment. Some agents like dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have shown promise. The tenuous kidney function in the early posttransplant period and lack of data limit the use of sodium-glucose cotransporter 2 inhibitors. There is a need for studies assessing noninsulin agents for EPTH to decrease risk of hypoglycemia associated with insulin and long-term complications of EPTH.
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Affiliation(s)
- Anira Iqbal
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Keren Zhou
- Department of Endocrinology, Diabetes & Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Sangeeta R Kashyap
- Department of Endocrinology, Diabetes & Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio
| | - M Cecilia Lansang
- Department of Endocrinology, Diabetes & Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio
- Corresponding author: M. Cecilia Lansang, MD, MPH, Department of Endocrinology, Diabetes & Metabolism, Cleveland Clinic Foundation, 9500 Euclid Avenue, F-20, Cleveland, Ohio 44195 Phone: 216-445-5246 x 4, Fax: (216) 445-1656,
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16
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Bashier AM, Kumar D, Alalawi FJ, Al Nour H, Al Hadari AK, Bin Hussain AA. Post-Transplant Diabetes: Prevalence, Risk, and Management Challenges. DUBAI DIABETES AND ENDOCRINOLOGY JOURNAL 2022. [DOI: 10.1159/000522092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
The prevalence of diabetes and diabetic nephropathy is increasing, especially in middle eastern countries. Many patients reach end-stage renal disease and either start dialysis or consider preemptive transplantation. Even a higher number of patients develop post-transplant diabetes, which imposes an even higher risk on graft survival and outcomes post-transplantation. Recently, in the UAE, a renal transplant service has been initiated. Because the population is considered at high risk for post-transplant diabetes, we wrote this review article to discuss the prevalence, risk factors, diagnostic criteria, and management, including lifestyle interventions, manipulation of immunosuppressant agents, and suggested algorithms for the use of oral hypoglycemic agents used in the management of post-transplantation diabetes mellitus. We also discussed the specific indications for each of the oral hypoglycemic agents.
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17
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Martinez Cantarin MP. Diabetes in Kidney Transplantation. Adv Chronic Kidney Dis 2021; 28:596-605. [PMID: 35367028 DOI: 10.1053/j.ackd.2021.10.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 10/11/2021] [Accepted: 10/12/2021] [Indexed: 11/11/2022]
Abstract
Diabetes mellitus (DM) is one of the most common complications after kidney transplantation and is associated with unfavorable outcomes including death. DM can be present before transplant but post-transplant DM (PTDM) refers to diabetes that is diagnosed after solid organ transplantation. Despite its high prevalence, optimal treatment to prevent complications of PTDM is unknown. Medical therapy of pre-existent DM or PTDM after transplant is challenging because of frequent interactions between antidiabetic and immunosuppressive agents. There is also frequent need for medication dose adjustments due to residual kidney disease and a higher risk of medication side effects in patients treated with immunosuppressive agents. Sodium-glucose cotransporter 2 inhibitors have demonstrated a favorable cardio-renal profile in patients with DM without a transplant and hence hold great promise in this patient population although there is concern about the higher risk of urinary tract infections. The significant gaps in our understanding of the pathophysiology, diagnosis, and management of DM after kidney transplantation need to be urgently addressed.
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18
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Yugueros González A, Kanter J, Sancho A, Gavela E, Solá E, Ávila A, Pallardó LM. Institutional Experience With New Antidiabetic Drugs in Kidney Transplant. Transplant Proc 2021; 53:2678-2680. [PMID: 34615601 DOI: 10.1016/j.transproceed.2021.08.042] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 08/25/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND The recent introduction of new antidiabetic drugs, analogs of glucagon-like peptide-1 (GLP-1) and sodium-glucose cotransporter 2 inhibitors, has shown excellent results in the management of patients with diabetes with chronic kidney disease. However, documented results of these medications in the population that has undergone kidney transplant are sparse. We report our institutional experience with them, including occurrence of side effects and possible interactions with immunosuppressive medications. METHODS A retrospective analysis of 15 patients (10 with diabetes and 5 without diabetes but with obesity) managed with these medications was carried out in the kidney transplant unit of Hospital Doctor Peset during the year 2019. Data acquired at baseline and 3, 6, and 12 months were analyzed. RESULTS The median hemoglobin A1c at baseline was 6.7 (interquartile range [IQR] = 5.8-8.2) and at 12 months it was 6 (IQR = 5.3-8.1, P = .96). The mean weight difference at 12 months was a loss of 7.2 ± 6 kg; median body mass index at baseline was 31.2 kg/m2 (IQR = 29.7-35.5) and 29.5 kg/m2 (IQR = 27.6-31.6, P = .01) at 12 months. In addition to weight loss, a reduction in insulin and oral antidiabetic drug requirements was observed. No significant changes were detected in serum creatinine or proteinuria values and the immunosuppressant levels remained stable. No acute rejection episodes were observed. CONCLUSION Based on our experience, the new antidiabetic drugs are safe, with no significant changes in renal function or immunosuppressant levels or clinically important adverse effects.
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Affiliation(s)
| | - Julia Kanter
- Nephrology Department, Hospital Doctor Peset, Valencia, Spain
| | - Asunción Sancho
- Nephrology Department, Hospital Doctor Peset, Valencia, Spain
| | - Eva Gavela
- Nephrology Department, Hospital Doctor Peset, Valencia, Spain
| | - Eva Solá
- Endocrinology Department, Hospital Doctor Peset, Valencia, Spain
| | - Ana Ávila
- Nephrology Department, Hospital Doctor Peset, Valencia, Spain
| | - Luis M Pallardó
- Nephrology Department, Hospital Doctor Peset, Valencia, Spain
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19
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Ben-David E, Hull R, Banerjee D. Diabetes mellitus in dialysis and renal transplantation. Ther Adv Endocrinol Metab 2021; 12:20420188211048663. [PMID: 34631007 PMCID: PMC8495524 DOI: 10.1177/20420188211048663] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 08/29/2021] [Indexed: 12/31/2022] Open
Abstract
Diabetes mellitus is the commonest cause of end-stage kidney failure worldwide and is a proven and significant risk factor for the development of cardiovascular disease. Renal impairment has a significant impact on the physiology of glucose homeostasis as it reduces tissue sensitivity to insulin and reduces insulin clearance. Renal replacement therapy itself affects glucose control: peritoneal dialysis may induce hyperglycaemia due to glucose-rich dialysate and haemodialysis often causes hypoglycaemia due to the relatively low concentration of glucose in the dialysate. Autonomic neuropathy which is common in chronic kidney disease (CKD) and diabetes increases the risk for asymptomatic hypoglycaemia. Pharmacological options for improving glycaemic control are limited due to alterations to drug metabolism. Impaired glucose tolerance and diabetes are also common in the post-kidney-transplant setting and increase the risk of graft failure and mortality. This review seeks to summarise the literature and tackle the intricacies of glycaemic management in patients with CKD who are either on maintenance haemodialysis or have received a kidney transplant. It outlines changes to glycaemic targets, monitoring of glycaemic control, the use of oral hypoglycaemic agents, the management of severe hyperglycaemia in dialysis and kidney transplantation patients.
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Affiliation(s)
- Eyal Ben-David
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Richard Hull
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Debasish Banerjee
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, Room G2.113, Second Floor, Grosvenor Wing, Blackshaw Road, Tooting, London SW17 0QT, UK
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20
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Phillips J, Chen JHC, Ooi E, Prunster J, Lim WH. Global Epidemiology, Health Outcomes, and Treatment Options for Patients With Type 2 Diabetes and Kidney Failure. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2021; 2:731574. [PMID: 36994340 PMCID: PMC10012134 DOI: 10.3389/fcdhc.2021.731574] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Accepted: 07/29/2021] [Indexed: 12/15/2022]
Abstract
The burden of type 2 diabetes and related complications has steadily increased over the last few decades and is one of the foremost global public health threats in the 21st century. Diabetes is one of the leading causes of chronic kidney disease and kidney failure and is an important contributor to the cardiovascular morbidity and mortality in this population. In addition, up to one in three patients who have received kidney transplants develop post-transplant diabetes, but the management of this common complication continues to pose a significant challenge for clinicians. In this review, we will describe the global prevalence and temporal trend of kidney failure attributed to diabetes mellitus in both developing and developed countries. We will examine the survival differences between treated kidney failure patients with and without type 2 diabetes, focusing on the survival differences in those on maintenance dialysis or have received kidney transplants. With the increased availability of novel hypoglycemic agents, we will address the potential impacts of these novel agents in patients with diabetes and kidney failure and in those who have developed post-transplant diabetes.
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Affiliation(s)
- Jessica Phillips
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia
- *Correspondence: Jessica Phillips,
| | - Jenny H. C. Chen
- School of Medicine, University of Wollongong, Wollongong, NSW, Australia
- Depatment of Nephrology, Wollongong Hospital, Wollongong, NSW, Australia
| | - Esther Ooi
- School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia
| | - Janelle Prunster
- Department of Renal Medicine, Cairns Hospital, Cairns, QLD, Australia
| | - Wai H. Lim
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia
- Medical School, University of Western Australia, Perth, WA, Australia
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21
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Nissaisorakarn P, Pavlakis M, Aala A. Novel Glucose-Lowering Therapies in the Setting of Solid Organ Transplantation. Adv Chronic Kidney Dis 2021; 28:361-370. [PMID: 34922692 DOI: 10.1053/j.ackd.2021.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/27/2021] [Accepted: 03/01/2021] [Indexed: 11/11/2022]
Abstract
Post-transplant diabetes mellitus is a frequent consequence of or a pre-existing comorbidity in solid organ transplantation (SOT) that is associated with greater morbidity and mortality. Novel glucose-lowering agents that have been shown to have cardiovascular morbidity/mortality benefit and renal protective effects such as sodium glucose transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists are being incorporated into new standard of care for diabetes mellitus. There is a paucity of data regarding the use of these agents in SOT. In this article, we will aim to review available literature on newer glucose-lowering therapeutics in SOT, mainly sodium glucose transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, their mechanism of action, benefits, risks, and safety profiles.
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22
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Ertuglu LA, Porrini E, Hornum M, Demiray A, Afsar B, Ortiz A, Covic A, Rossing P, Kanbay M. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors for diabetes after solid organ transplantation. Transpl Int 2021; 34:1341-1359. [PMID: 33880815 DOI: 10.1111/tri.13883] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/22/2021] [Accepted: 04/12/2021] [Indexed: 12/13/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation and a major cause of increased morbidity and mortality. Additionally, solid organ transplant patients may have pre-existent type 2 diabetes mellitus (T2DM). While insulin is the treatment of choice for hyperglycemia in the first weeks after transplantation, there is no preferred first line agent for long-term management of PTDM or pre-existent T2DM. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight, and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits. Furthermore, the mechanisms of action of GLP-1RA may counteract some of the driving forces for PTDM, as calcineurin-induced β cell toxicity as per preclinical data, and improve obesity. However, their use in the treatment of PTDM is currently limited by a paucity of data. Retrospective observational and small exploratory studies suggest that GLP-1RA effectively improve glycemic control and induce weight loss in patients with PTDM without interacting with commonly used immunosuppressive agents, although randomized-controlled clinical trials are required to confirm their safety and efficacy. In this narrative review, we evaluate the risk factors and pathogenesis of PTDM and compare the potential roles of GLP-1RA and SGLT2 inhibitors in PTDM prevention and management as well as in pre-existent T2DM, and providing a roadmap for evidence generation on newer antidiabetic drugs for solid organ transplantation.
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Affiliation(s)
- Lale A Ertuglu
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Esteban Porrini
- Red de Investigación Renal (REDINREN), Instituto Carlos III-FEDER, Tenerife, Spain.,Department of Medicine, Hospital Universitario de Canarias, Tenerife, Spain.,Instituto de Tecnologías Biomédicas, University of La Laguna, Tenerife, Spain
| | - Mads Hornum
- Department of Nephrology, Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Atalay Demiray
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Baris Afsar
- Division of Nephrology, Department of Internal Medicine, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Alberto Ortiz
- IIS-Fundacion Jimenez Diaz, Department of Medicine, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain
| | - Adrian Covic
- Department of Nephrology, Grigore T. Popa' University of Medicine, Iasi, Romania
| | - Peter Rossing
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Steno Diabetes Center Copenhagen, Copenhagen, Denmark
| | - Mehmet Kanbay
- Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
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23
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Martin-Moreno PL, Shin HS, Chandraker A. Obesity and Post-Transplant Diabetes Mellitus in Kidney Transplantation. J Clin Med 2021; 10:2497. [PMID: 34198724 PMCID: PMC8201168 DOI: 10.3390/jcm10112497] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/30/2021] [Accepted: 06/01/2021] [Indexed: 12/14/2022] Open
Abstract
Worldwide, the prevalence obesity, diabetes, and chronic kidney disease is increasing apace. The relationship between obesity and chronic kidney disease is multidimensional, especially when diabetes is also considered. The optimal treatment of patients with chronic kidney disease includes the need to consider weight loss as part of the treatment. The exact relationship between obesity and kidney function before and after transplantation is not as clear as previously imagined. Historically, patients with obesity had worse outcomes following kidney transplantation and weight loss before surgery was encouraged. However, recent studies have found less of a correlation between obesity and transplant outcomes. Transplantation itself is also a risk factor for developing diabetes, a condition known as post-transplant diabetes mellitus, and is related to the use of immunosuppressive medications and weight gain following transplantation. Newer classes of anti-diabetic medications, namely SGLT-2 inhibitors and GLP-1 agonists, are increasingly being recognized, not only for their ability to control diabetes, but also for their cardio and renoprotective effects. This article reviews the current state of knowledge on the management of obesity and post-transplant diabetes mellitus for kidney transplant patients.
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Affiliation(s)
- Paloma Leticia Martin-Moreno
- Department of Nephrology, Clinica Universidad de Navarra, Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain
| | - Ho-Sik Shin
- Renal Division, Department of Internal Medicine, Gospel Hospital, Kosin University, Busan 49267, Korea;
- Transplantation Research Institute, Kosin University College of Medicine, Busan 49367, Korea
| | - Anil Chandraker
- Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
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24
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Montada-Atin T, Prasad GVR. Recent advances in new-onset diabetes mellitus after kidney transplantation. World J Diabetes 2021; 12:541-555. [PMID: 33995843 PMCID: PMC8107982 DOI: 10.4239/wjd.v12.i5.541] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/05/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
A common challenge in managing kidney transplant recipients (KTR) is post-transplant diabetes mellitus (PTDM) or diabetes mellitus (DM) newly diagnosed after transplantation, in addition to known pre-existing DM. PTDM is an important risk factor for post-transplant cardiovascular (CV) disease, which adversely affects patient survival and quality of life. CV disease in KTR may manifest as ischemic heart disease, heart failure, and/or left ventricular hypertrophy. Available therapies for PTDM include most agents currently used to treat type 2 diabetes. More recently, the use of sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase 4 inhibitors (DPP4i) has cautiously extended to KTR with PTDM, even though KTR are typically excluded from large general population clinical trials. Initial evidence from observational studies seems to indicate that SGLT2i, GLP-1 RA, and DPP4i may be safe and effective for glycemic control in KTR, but their benefit in reducing CV events in this otherwise high-risk population remains unproven. These newer drugs must still be used with care due to the increased propensity of KTR for intravascular volume depletion and acute kidney injury due to diarrhea and their single-kidney status, pre-existing burden of peripheral vascular disease, urinary tract infections due to immunosuppression and a surgically altered urinary tract, erythrocytosis from calcineurin inhibitors, and reduced kidney function from acute or chronic rejection.
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Affiliation(s)
- Tess Montada-Atin
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, Ontario, Canada
| | - G V Ramesh Prasad
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto M5C 2T2, Canada
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25
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Brown SA, Izzy M, Watt KD. Pharmacotherapy for Weight Loss in Cirrhosis and Liver Transplantation: Translating the Data and Underused Potential. Hepatology 2021; 73:2051-2062. [PMID: 33047343 DOI: 10.1002/hep.31595] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 08/30/2020] [Accepted: 09/24/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to >40% post-transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine-topiramate, naltrexone-bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs). APPROACH AND RESULTS While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine-topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed. CONCLUSIONS The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co-morbidities, and concomitant medications.
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Affiliation(s)
- Sara A Brown
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University, Nashville, TN, USA
| | - Manhal Izzy
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University, Nashville, TN, USA
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, The Mayo Clinic, Rochester, MN, USA
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26
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Oikonomaki D, Dounousi E, Duni A, Roumeliotis S, Liakopoulos V. Incretin based therapies and SGLT-2 inhibitors in kidney transplant recipients with diabetes: A systematic review and meta-analysis. Diabetes Res Clin Pract 2021; 172:108604. [PMID: 33338553 DOI: 10.1016/j.diabres.2020.108604] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 08/31/2020] [Accepted: 12/01/2020] [Indexed: 12/18/2022]
Abstract
AIMS We aimed to conduct a systematic review and meta-analysis regarding the use of incretin-based therapies including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists as well as sodium-glucose co-transporter-2 (SGLT2) inhibitorsin persons with posttransplantation diabetes mellitus (PTDM) so as to assess both their efficacy and safety. METHODS We searched for publications on Kidney/Renal Transplantation and DPP-4 inhibitors, GLP-1-receptor agonists and SGLT-2 inhibitors and included every study using these antidiabetics. A p-value < 0.05 was considered statistical significant. RESULTS Sixteen studies and 310 individuals with a mean age of 55.98 ± 8.81 years were included in the analysis. Participants received DPP-4 inhibitors in 8 studies, SGLT-2 inhibitors in 6 studies and GLP-1 receptor agonists in 2 studies, with a mean follow-up of 22.03 ± 14.95 weeks. Hemoglobin A1c (HbA1c) reduction was demonstrated in 10 studies (mean +/- standard deviation (MD) = - 0.38%, I2 = 45%). MD of HbA1c was -0.3741 and -0.4596 mg/dl for DPP-4 inhibitors and SGLT-2 inhibitors respectively. Nine studies demonstrated differences in fasting plasma glucose (FPG) (MD = - 25,76) and 5 studies in post-prandial glucose (PPG) (MD = - 6.61) before and following treatment. Most studies did not show adverse effects on the glomerular filtration rate (GFR) and hepatic function. CONCLUSIONS DPP-4 inhibitors and SGLT2 inhibitors appear both efficacious and safe in renal transplant recipients. More high-quality studies are required to guide therapeutic choices for PTDM.
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Affiliation(s)
- Dora Oikonomaki
- Department of Nephrology, Evaggelismos General Hospital, Athens, Greece
| | - Evangelia Dounousi
- Department of Nephrology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece.
| | - Anila Duni
- Department of Nephrology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Stefanos Roumeliotis
- Division of Nephrology and Hypertension, 1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Vassilios Liakopoulos
- Division of Nephrology and Hypertension, 1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
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27
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Sanyal D, Biswas M, Chaudhari N. Long-term efficacy and safety of anti-hyperglycaemic agents in new-onset diabetes after transplant: Results from outpatient-based 1-year follow-up and a brief review of treatment options. Diabetes Metab Syndr 2021; 15:13-19. [PMID: 33278690 DOI: 10.1016/j.dsx.2020.11.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 10/14/2020] [Accepted: 11/20/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Evaluation of long-term efficacy and safety of various anti-hyperglycaemic agents (AHA) for glycaemic control in NODAT, in stable kidney transplant recipients (KTRs) during 1-year outpatient follow-up. METHODS We collected FPG, PPG, HbA1c, serum creatinine, eGFR, blood tacrolimus level, hypoglycaemia and body weight values from an existing database of KTRs diagnosed to have NODAT. Those newly initiated on AHA over 3 months post-transplant; received standard triple immunosuppressive therapy; and followed up for 1-year after referral, were included. RESULTS In ninety-five patients' (Male = 65), mean decrease at 1-year from baseline in FPG (185.01 ± 62.11 mg/dL), PPG (293.21 ± 85.23 mg/dL) and HbA1c (8.48 ± 1.08%) was 67.09, 126.11 and 1.4 respectively (p < 0.0001). At 1-year, mean HbA1c was 7.08 ± 0.38%, ninety-one patients achieving HbA1c ≤ 7.5%. Fifty-two patients received oral combination therapy based on linagliptin/metformin/repaglinide/gliclazide, 19 received insulin-based regimen, and 24 received linagliptin monotharapey. Thirty patients reported hypoglycaemia (10 with gliclazide and 15 with insulin) and fifty patients gained body-weight at 1-year. Mean serum creatinine and eGFR significantly improved by 0.29 and 15.77 from baseline of 1.56 ± 0.62 mg/dL and 53.95 ± 16.10 mL/min/1.73 m2 respectively. CONCLUSIONS Significant proportion of NODAT patients achieved long-term glycemic control with improved renal function. Combination therapy was needed in most within 1-year. Linagliptin monotherapy was effective, without producing hypoglycaemia or weight gain.
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Affiliation(s)
- Debmalya Sanyal
- Department of Endocrinology, KPC Medical College and Hospital, RN Tagore International Institute of Cardiac Sciences, Kolkata, India.
| | - Mansij Biswas
- Department of Medical Affairs, Boehringer Ingelheim, Mumbai, India
| | - Nayan Chaudhari
- Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai, India
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28
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Hecking M, Sharif A, Eller K, Jenssen T. Management of post-transplant diabetes: immunosuppression, early prevention, and novel antidiabetics. Transpl Int 2021; 34:27-48. [PMID: 33135259 PMCID: PMC7839745 DOI: 10.1111/tri.13783] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/20/2020] [Accepted: 10/29/2020] [Indexed: 12/12/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) shows a relationship with risk factors including obesity and tacrolimus-based immunosuppression, which decreases pancreatic insulin secretion. Several of the sodium-glucose-linked transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) dramatically improve outcomes of individuals with type 2 diabetes with and without chronic kidney disease, which is, as heart failure and atherosclerotic cardiovascular disease, differentially affected by both drug classes (presumably). Here, we discuss SGLT2is and GLP1-RAs in context with other PTDM management strategies, including modification of immunosuppression, active lifestyle intervention, and early postoperative insulin administration. We also review recent studies with SGLT2is in PTDM, reporting their safety and antihyperglycemic efficacy, which is moderate to low, depending on kidney function. Finally, we reference retrospective case reports with GLP1-RAs that have not brought forth major concerns, likely indicating that GLP1-RAs are ideal for PTDM patients suffering from obesity. Although our article encompasses PTDM after solid organ transplantation in general, data from kidney transplant recipients constitute the largest proportion. The PTDM research community still requires data that treating and preventing PTDM will improve clinical conditions beyond hyperglycemia. We therefore suggest that it is time to collaborate, in testing novel antidiabetics among patients of all transplant disciplines.
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Affiliation(s)
- Manfred Hecking
- Department of Internal Medicine IIIClinical Division of Nephrology & DialysisMedical University of ViennaViennaAustria
| | - Adnan Sharif
- Department of Nephrology and TransplantationQueen Elizabeth HospitalBirminghamUK
| | - Kathrin Eller
- Clinical Division of NephrologyMedical University of GrazGrazAustria
| | - Trond Jenssen
- Department of Organ TransplantationOslo University HospitalRikshospitaletOsloNorway
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29
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Anderson S, Cotiguala L, Tischer S, Park JM, McMurry K. Review of Newer Antidiabetic Agents for Diabetes Management in Kidney Transplant Recipients. Ann Pharmacother 2020; 55:496-508. [PMID: 32795145 DOI: 10.1177/1060028020951955] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE This systematic review describes the efficacy, safety, and drug interactions of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose transport protein 2 (SGLT2) inhibitors in kidney transplant recipients (KTRs). DATA SOURCES Articles were identified by English-language MEDLINE search, published prior to May 2020, using the terms kidney transplant, OR PTDM, OR NODAT, AND metformin, OR DPP4, OR GLP1, OR SGLT2. STUDY SELECTION AND DATA EXTRACTION All selected studies were included if the study population was composed of adult KTRs who were diagnosed with either impaired glucose tolerance, diabetes mellitus (DM), new-onset diabetes after transplant (NODAT), or posttransplantation diabetes mellitus (PTDM). DATA SYNTHESIS In KTRs, there is evidence for safety with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors. However, urinary tract infections and a slight initial decrease in renal function may limit use of SGLT2 inhibitors. As compared with the nontransplant type 2 DM population, SGLT2 inhibitors are not as efficacious in KTRs. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE This review provides an overview of the current literature on newer antidiabetic agents, addressing efficacy, safety, and drug interactions to help guide clinical decision-making for their use in KTRs. CONCLUSION Newer antidiabetic agents have been recommended by the American Diabetes Association for potential cardiovascular, renal, and hypoglycemic benefits. Particular agents, such as DPP-4 inhibitors and GLP-1 RAs may play a role in correcting PTDM-related defects. Clinicians need to take into account both patient-specific and drug-specific characteristics when initiating these agents in KTRs.
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30
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Aleksic S, Eisenberg R, Tsomos E, Zahedpour Anaraki S, Japp E, Upadhyay L, Mowrey WB, Akalin E, Zonszein J. Glycemic management and clinical outcomes in underserved minority kidney transplant recipients with type 2 and posttransplantation diabetes: A single-center retrospective study. Diabetes Res Clin Pract 2020; 165:108221. [PMID: 32442553 PMCID: PMC7415727 DOI: 10.1016/j.diabres.2020.108221] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 04/28/2020] [Accepted: 05/12/2020] [Indexed: 01/20/2023]
Abstract
AIMS Little is known about glycemic management, particularly with novel cardio-nephroprotecive agents, in underserved minority kidney transplant recipients with pre-transplant type 2 (T2DM) and posttransplantation diabetes mellitus (PTDM). We assessed glycemic management and outcomes in this high-risk population. METHODS We reviewed records of patients who received kidney transplants between June 2012 and December 2014 at a single center. Hemoglobin A1c (HbA1c) and prescribed glucose-lowering medications were examined, and mortality was compared between T2DM, PTDM, and no diabetes (NoDM) patients. RESULTS We followed 302 patient records (41.1% Hispanic, 41.1% non-Hispanic black) for a median (IQR) of 45.5 (37.0, 53.0) months post-transplant. Pre-transplant T2DM was present in 152 (50.3%), while 58 (19.2%) developed PTDM and 92 (30.4%) remained NoDM. At 1-year post-transplant, the average HbA1c was 8.1 ± 1.8% in T2DM and 6.6 ± 1.3% in PTDM. No glucose-lowering agents were prescribed in 3.4% of T2DM and 44.8% of PTDM. When treated, both received mostly insulin and metformin. Diabetes, HbA1c and insulin therapy were not independently associated with risk of mortality. CONCLUSIONS Glycemic management was suboptimal and relied on older medications. Further studies are needed to assess longer-term outcomes of more rigorous glycemic management, and the value of novel cardio-nephroprotective agents in kidney transplant recipients.
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Affiliation(s)
- Sandra Aleksic
- Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, NY, United States.
| | - Ruth Eisenberg
- Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Effie Tsomos
- Department of Medicine, Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai Medical Center, New York, NY, United States
| | - Sara Zahedpour Anaraki
- Department of Medicine, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, NY, United States
| | - Emily Japp
- Department of Medicine, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, NY, United States
| | - Laxmi Upadhyay
- Department of Medicine, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, NY, United States
| | - Wenzhu Bi Mowrey
- Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Enver Akalin
- Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, NY, United States
| | - Joel Zonszein
- Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, NY, United States
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Cigrovski Berkovic M, Virovic-Jukic L, Bilic-Curcic I, Mrzljak A. Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management. World J Gastroenterol 2020; 26:2740-2757. [PMID: 32550751 PMCID: PMC7284186 DOI: 10.3748/wjg.v26.i21.2740] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 04/24/2020] [Accepted: 05/14/2020] [Indexed: 02/06/2023] Open
Abstract
Liver cirrhosis and diabetes mellitus (DM) are both common conditions with significant socioeconomic burden and impact on morbidity and mortality. A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications. Type 2 DM (T2DM) is a well-recognized risk factor for chronic liver disease and vice-versa, DM may develop as a complication of cirrhosis, irrespective of its etiology. Liver transplantation (LT) represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease (NAFLD), which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM. The metabolic risk factors including immunosuppressive drugs, can contribute to persistent or de novo development of DM and NAFLD after LT. T2DM, obesity, cardiovascular morbidities and renal impairment, frequently associated with metabolic syndrome and NAFLD, may have negative impact on short and long-term outcomes following LT. The treatment of DM in the context of chronic liver disease and post-transplant is challenging, but new emerging therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.
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Affiliation(s)
- Maja Cigrovski Berkovic
- Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Dubrava, Zagreb 10000, Croatia
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
| | - Lucija Virovic-Jukic
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Division of Gastroenterology and Hepatology, Sisters of Charity University Hospital, Zagreb 10000, Croatia
| | - Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Center Osijek, Osijek 31000, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
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32
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Cohen E, Korah M, Callender G, Belfort de Aguiar R, Haakinson D. Metabolic Disorders with Kidney Transplant. Clin J Am Soc Nephrol 2020; 15:732-742. [PMID: 32284323 PMCID: PMC7269213 DOI: 10.2215/cjn.09310819] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Metabolic disorders are highly prevalent in kidney transplant candidates and recipients and can adversely affect post-transplant graft outcomes. Management of diabetes, hyperparathyroidism, and obesity presents distinct opportunities to optimize patients both before and after transplant as well as the ability to track objective data over time to assess a patient's ability to partner effectively with the health care team and adhere to complex treatment regimens. Optimization of these particular disorders can most dramatically decrease the risk of surgical and cardiovascular complications post-transplant. Approximately 60% of nondiabetic patients experience hyperglycemia in the immediate post-transplant phase. Multiple risk factors have been identified related to development of new onset diabetes after transplant, and it is estimated that upward of 7%-30% of patients will develop new onset diabetes within the first year post-transplant. There are a number of medications studied in the kidney transplant population for diabetes management, and recent data and the risks and benefits of each regimen should be optimized. Secondary hyperparathyroidism occurs in most patients with CKD and can persist after kidney transplant in up to 66% of patients, despite an initial decrease in parathyroid hormone levels. Parathyroidectomy and medical management are the options for treatment of secondary hyperparathyroidism, but there is no randomized, controlled trial providing clear recommendations for optimal management, and patient-specific factors should be considered. Obesity is the most common metabolic disorder affecting the transplant population in both the pre- and post-transplant phases of care. Not only does obesity have associations and interactions with comorbid illnesses, such as diabetes, dyslipidemia, and cardiovascular disease, all of which increase morbidity and mortality post-transplant, but it also is intimately inter-related with access to transplantation for patients with kidney failure. We review these metabolic disorders and their management, including data in patients with kidney transplants.
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Affiliation(s)
- Elizabeth Cohen
- Department of Pharmacy, Yale-New Haven Hospital, New Haven, Connecticut
| | - Maria Korah
- Yale University School of Medicine, New Haven, Connecticut
| | - Glenda Callender
- Department of Surgery, Section of Endocrine Surgery, Yale University, New Haven, Connecticut
| | | | - Danielle Haakinson
- Department of Surgery, Section of Transplant, Yale University, New Haven, Connecticut
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33
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Abstract
Solid organ transplantation (SOT) is an established therapeutic option for chronic disease resulting from end-stage organ dysfunction. Long-term use of immunosuppression is associated with post-transplantation diabetes mellitus (PTDM), placing patients at increased risk of infections, cardiovascular disease and mortality. The incidence rates for PTDM have varied from 10 to 40% between different studies. Diagnostic criteria have evolved over the years, as a greater understating of PTDM has been reached. There are differences in pathophysiology and clinical course of type 2 diabetes and PTDM. Hence, managing this condition can be a challenge for a diabetes physician, as there are several factors to consider when tailoring therapy for post-transplant patients to achieve better glycaemic as well as long-term transplant outcomes. This article is a detailed review of PTDM, examining the pathogenesis, diagnostic criteria and management in light of the current evidence. The therapeutic options are discussed in the context of their safety and potential drug-drug interactions with immunosuppressive agents.
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Affiliation(s)
| | - Kathryn Biddle
- St George's University Hospitals NHS Foundation Trust, London, UK
| | | | - Shazli Azmi
- Manchester University NHS Foundation Trust, Manchester, UK
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34
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Thangavelu T, Lyden E, Shivaswamy V. A Retrospective Study of Glucagon-Like Peptide 1 Receptor Agonists for the Management of Diabetes After Transplantation. Diabetes Ther 2020; 11:987-994. [PMID: 32072430 PMCID: PMC7136376 DOI: 10.1007/s13300-020-00786-1] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Management of post-transplant diabetes mellitus is challenging; there is a lack of prospective randomized controlled trials for safety and efficacy of antidiabetic medications in solid organ recipients. Glucagon-like peptide 1 receptor agonists (GLP-1RA) are a relatively new class of medications used to manage type 2 diabetes in the general population. They have several benefits besides glycemic control, including weight loss and improved cardiovascular risk. However, they have not been studied extensively in the post-transplant population for safety and efficacy. METHODS We conducted a retrospective study of patients who had received kidney, liver, or heart transplant, had diabetes either pre- or post-transplant, and were treated with GLP-1RA. We identified seven kidney, seven liver, and five heart transplant recipients who had received GLP-1RA. We assessed changes in immunosuppressant levels, rejection episodes, changes in hemoglobin A1c (HbA1c), weight, and body mass index (BMI) while on the GLP-1RA. We also looked at changes in insulin dose, other diabetes medications, heart rate, blood pressure, and renal function. RESULTS After a mean follow-up period of 12 months, there were no significant changes in tacrolimus (FK506) levels and renal function for the period of GLP-1RA use. At the end of 12 months, the mean drop in weight was 4.86 kg [95% CI - 7.79, - 1.93]. The BMI decreased by a mean of 1.63 kg/m2 at the end of 12 months [95% CI - 2.53, - 0.73]. HbA1c decreased from baseline by 1.08% [95% CI - 1.65, - 0.51], 0.96% [95% CI - 1.68, - 0.25], and 0.75% [95% CI - 1.55, 0.05] at 3, 6, and 12 months, respectively. CONCLUSIONS Our data suggest that GLP-1RA do not affect tacrolimus levels or transplant outcomes in solid organ transplant (SOT) recipients in the short term. GLP-1RA also seem to be as effective in SOT recipients for glycemic control and weight loss as in the non-transplant population with diabetes.
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Affiliation(s)
- Thiyagarajan Thangavelu
- Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Nebraska Medical Center, Omaha, NE, USA
| | - Elizabeth Lyden
- Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA
| | - Vijay Shivaswamy
- Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Nebraska Medical Center, Omaha, NE, USA.
- VA Nebraska, Western Iowa Health Care System, Omaha, NE, USA.
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The Use of GLP1R Agonists for the Treatment of Type 2 Diabetes in Kidney Transplant Recipients. Transplant Direct 2020; 6:e524. [PMID: 32095510 PMCID: PMC7004635 DOI: 10.1097/txd.0000000000000971] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 11/25/2019] [Indexed: 12/16/2022] Open
Abstract
Glucagon-like peptide-1 receptor agonists (GLP1RA) have been shown to improve glucose control and diabetes-related comorbidities in patients without solid organ transplants. The effectiveness, safety, and tolerability of GLP1RA after kidney transplantation have not been adequately studied.
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Tsai SF, Chen CH. Management of Diabetes Mellitus in Normal Renal Function, Renal Dysfunction and Renal Transplant Recipients, Focusing on Glucagon-Like Peptide-1 Agonist: A Review Based upon Current Evidence. Int J Mol Sci 2019; 20:ijms20133152. [PMID: 31261624 PMCID: PMC6651241 DOI: 10.3390/ijms20133152] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 06/23/2019] [Accepted: 06/27/2019] [Indexed: 12/22/2022] Open
Abstract
Diabetes Mellitus (DM) is a leading cause of both Cardiovascular Disease (CVD) and End-stage Renal Disease (ESRD). After 2008, there has been much evidence presented, and recently the guidelines for sugar control have changed to focus on being more disease orientated. GLP-1 Receptor Agonists (GLP-1R) and sodium glucose cotransporter-2 inhibitors are suggested as the first line towards fighting all DM, CVD and ESRD. However, the benefits of GLP-1R in organ transplantation recipients remain very limited. No clinical trials have been designed for this particular population. GLP-1R, a gastrointestinal hormone of the incretin family, possesses antidiabetic, antihypertensive, anti-inflammatory, anti-apoptotic and immunomodulatory actions. There are few drug–drug interactions, with delayed gastric emptying being the major concern. The trough level of tacrolimus may not be significant but should still be closely monitored. There are some reasons which support GLP-1R in recipients seeking glycemic control. Post-transplant DM is due to an impaired β-cell function and glucose-induced glucagon suppression during hyperglycemia, which can be reversed by GLP-1R. GLP-1R infusion tends to relieve immunosuppressant related toxicity. Until now, in some cases, glycemic control and body weight reduction can be anticipated with GLP-1R. Additional renal benefits have also been reported. Side effects of hypoglycemia and gastrointestinal discomfort were rarely reported. In conclusion, GLP-1R could be implemented for recipients while closely monitoring their tacrolimus levels and any potential side effects. Any added benefits, in addition to sugar level control, still require more well-designed studies to prove their existence.
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Affiliation(s)
- Shang-Feng Tsai
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan
- Department of Life Science, Tunghai University, Taichung 407, Taiwan
- School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
| | - Cheng-Hsu Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan.
- Department of Life Science, Tunghai University, Taichung 407, Taiwan.
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Singh P, Pesavento TE, Washburn K, Walsh D, Meng S. Largest single-centre experience of dulaglutide for management of diabetes mellitus in solid organ transplant recipients. Diabetes Obes Metab 2019; 21:1061-1065. [PMID: 30565376 DOI: 10.1111/dom.13619] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 12/06/2018] [Accepted: 12/07/2018] [Indexed: 12/16/2022]
Abstract
Published data regarding the approach to management of diabetes mellitus in solid organ transplant (SOT) recipients are limited. We performed a retrospective chart review of SOT recipients with diabetes, above 18 years of age, who were usisng dulaglutide. There was a sustained, statistically significant reduction in the primary endpoints of weight, body mass index (BMI) and insulin requirement in 63 SOT recipients at 6, 12 and 24 months, respectively. A total of 59, 50 and 13 recipients were followed during 6, 12 and 24 months, with a mean paired difference for weight reduction of 2.07 (P value <0.003), 4.007 (P value <0.001) and 5.23 (P value <0.034) kgs and a BMI reduction of 0.80 (P value <0.001), 1.35 (P value <0.005) and 2.015 (P value <0.045) kg/m2 , respectively. The mean paired difference for insulin reduction before and after dulaglutide treatment was 5.94 units (P value <0.0002). There was no increased risk of malignancy, cardiovascular morbidity, graft-failure or all-cause mortality. Gastrointestinal manifestations were rare, even in patients with advanced chronic kidney disease (CKD), and required no change in immunosuppressive agents. Thus, dulaglutide may be considered an important option for diabetes management in SOT.
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Affiliation(s)
- Priyamvada Singh
- Comprehensive Transplant Center, Ohio State University, Columbus, Ohio
| | - Todd E Pesavento
- Comprehensive Transplant Center, Ohio State University, Columbus, Ohio
| | - Kenneth Washburn
- Comprehensive Transplant Center, Ohio State University, Columbus, Ohio
| | - Debbie Walsh
- Comprehensive Transplant Center, Ohio State University, Columbus, Ohio
| | - Shumei Meng
- Comprehensive Transplant Center, Ohio State University, Columbus, Ohio
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Abstract
Kidney transplantation (KT) is the most effective way to decrease the high morbidity and mortality of patients with end-stage renal disease. However, KT does not completely reverse the damage done by years of decreased kidney function and dialysis. Furthermore, new offending agents (in particular, immunosuppression) added in the post-transplant period increase the risk of complications. Cardiovascular (CV) disease, the leading cause of death in KT recipients, warrants pre-transplant screening based on risk factors. Nevertheless, the screening methods currently used have many shortcomings and a perfect screening modality does not exist. Risk factor modification in the pre- and post-transplant periods is of paramount importance to decrease the rate of CV complications post-transplant, either by lifestyle modification (for example, diet, exercise, and smoking cessation) or by pharmacological means (for example, statins, anti-hyperglycemics, and so on). Post-transplantation diabetes mellitus (PTDM) is a major contributor to mortality in this patient population. Although tacrolimus is a major contributor to PTDM development, changes in immunosuppression are limited by the higher risk of rejection with other agents. Immunosuppression has also been implicated in higher risk of malignancy; therefore, proper cancer screening is needed. Cancer immunotherapy is drastically changing the way certain types of cancer are treated in the general population; however, its use post-transplant is limited by the risk of allograft rejection. As expected, higher risk of infections is also encountered in transplant recipients. When caring for KT recipients, special attention is needed in screening methods, preventive measures, and treatment of infection with BK virus and cytomegalovirus. Hepatitis C virus infection is common in transplant candidates and in the deceased donor pool; however, newly developed direct-acting antivirals have been proven safe and effective in the pre- and post-transplant periods. The most important and recent developments on complications following KT are reviewed in this article.
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Affiliation(s)
- Abraham Cohen-Bucay
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico.,Nephrology Department, American British Cowdray Medical Center, Mexico City, 05300, Mexico
| | - Craig E Gordon
- Division of Nephrology, Tufts Medical Center, Boston, MA, 02111, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, MA, 02118, USA
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Grancini V, Resi V, Palmieri E, Pugliese G, Orsi E. Management of diabetes mellitus in patients undergoing liver transplantation. Pharmacol Res 2019; 141:556-573. [PMID: 30690071 DOI: 10.1016/j.phrs.2019.01.042] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 01/24/2019] [Accepted: 01/24/2019] [Indexed: 02/07/2023]
Abstract
Diabetes is a common feature in cirrhotic individuals both before and after liver transplantation and negatively affects prognosis. Certain aetiological agents of chronic liver disease and loss of liver function per se favour the occurrence of pre-transplant diabetes in susceptible individuals, whereas immunosuppressant treatment, changes in lifestyle habits, and donor- and procedure-related factors contribute to diabetes development/persistence after transplantation. Challenges in the management of pre-transplant diabetes include the profound nutritional alterations characterizing cirrhotic individuals and the limitations to the use of drugs with liver metabolism. Special issues in the management of post-transplant diabetes include the diabetogenic potential of immunosuppressant drugs and the increased cardiovascular risk characterizing solid organ transplant survivors. Overall, the pharmacological management of cirrhotic patients undergoing liver transplantation is complicated by the lack of specific guidelines reflecting the paucity of data on the impact of glycaemic control and the safety and efficacy of anti-hyperglycaemic agents in these individuals.
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Affiliation(s)
- Valeria Grancini
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Veronica Resi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Eva Palmieri
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, and Diabetes Unit, Sant'Andrea University Hospital, Rome, Italy
| | - Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
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Abstract
PURPOSE OF REVIEW The leading cause of death in both chronic kidney disease (CKD) and renal transplant patients is cardiovascular events. Post-transplant diabetes mellitus (PTx-DM), which is a major cardiovascular risk factor, is a metabolic disorder that affects 5.5-60.2% of renal allograft recipients by 1-year posttransplant (PTx). PTx-DM has been associated with a negative impact on patient and graft outcomes and survival. RECENT FINDINGS Individuals who develop PTx-DM are usually prone to this condition prior to and/or after developing CKD. Genetic factors, obesity, inflammation, medications and CKD all are risk factors for PTx-diabetes mellitus. The path to development of disease continues PTx frequently augmented by the use of diabetogenic maintenance immunosuppressive and some nonimmunosuppressive medications. These risk factors are usually associated with an increase in insulin resistance, a decrease in insulin gene expression and/or β-cell dysfunction and apoptosis. SUMMARY Some new anti-diabetes mellitus medications may help to improve the overall outcome; however, there is a real need for developing a preventive strategy. Identifying and targeting PTx-DM risk factors may help to guide the development of an effective programme. This could include the adoption of nondiabetogenic immunosuppressive protocols for high-risk patients.
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Conte C, Secchi A. Post-transplantation diabetes in kidney transplant recipients: an update on management and prevention. Acta Diabetol 2018; 55:763-779. [PMID: 29619563 DOI: 10.1007/s00592-018-1137-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 03/26/2018] [Indexed: 12/14/2022]
Abstract
Post-transplantation diabetes mellitus (PTDM) may severely impact both short- and long-term outcomes of kidney transplant recipients in terms of graft and patient survival. However, PTDM often goes undiagnosed is underestimated or poorly managed. A diagnosis of PTDM should be delayed until the patient is on stable maintenance doses of immunosuppressive drugs, with stable kidney graft function and in the absence of acute infections. Risk factors for PTDM should be assessed during the pre-transplant evaluation period, in order to reduce the likelihood of developing diabetes. The oral glucose tolerance test is considered as the gold standard for diagnosing PTDM, whereas HbA1c is not reliable during the first months after transplantation. Glycaemic targets should be individualised, and comorbidities such as dyslipidaemia and hypertension should be treated with drugs that have the least possible impact on glucose metabolism, at doses that do not interact with immunosuppressants. While insulin is the preferred agent for treating inpatient hyperglycaemia in the immediate post-transplantation period, little evidence is available to guide therapeutic choices in the management of PTDM. Metformin and incretins may offer some advantage over other glucose-lowering agents, particularly with respect to risk of hypoglycaemia and weight gain. Tailoring immunosuppressive regimens may be of help, although maintenance of good kidney function should be prioritised over prevention/treatment of PTDM. The aim of this narrative review is to provide an overview of the available evidence on management and prevention of PTDM, with a focus on the available therapeutic options.
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Affiliation(s)
- Caterina Conte
- I.R.C.C.S. Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
| | - Antonio Secchi
- I.R.C.C.S. Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy
- Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy
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Peláez-Jaramillo MJ, Cárdenas-Mojica AA, Gaete PV, Mendivil CO. Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment. Diabetes Ther 2018; 9:521-543. [PMID: 29411291 PMCID: PMC6104273 DOI: 10.1007/s13300-018-0374-8] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Indexed: 02/08/2023] Open
Abstract
Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM. A diagnosis of PLTDM should be established only after doses of CNI and steroids are stable and the post-operative stress has been overcome. The predominant defect induced by CNI is insulin secretory dysfunction. Plasma glucose control must start immediately after the transplant procedure in order to improve long-term results for both patient and transplant. Among the better known antidiabetics, metformin and DPP-4 inhibitors have a particularly benign profile in the PLTDM context and are the preferred oral agents for long-term management. Insulin therapy is also an effective approach that addresses the prevailing pathophysiological defect of the disorder. There is still insufficient evidence about the impact of newer families of antidiabetics (GLP-1 agonists, SGLT-2 inhibitors) on PLTDM. In this review, we summarize current knowledge on the epidemiology, pathogenesis, course of disease and medical management of PLTDM.
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Affiliation(s)
| | | | - Paula V Gaete
- Universidad de los Andes School of Medicine, Bogotá, Colombia
| | - Carlos O Mendivil
- Universidad de los Andes School of Medicine, Bogotá, Colombia.
- Endocrinology Section, Department of Internal Medicine, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
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Liou JH, Liu YM, Chen CH. Management of Diabetes Mellitus With Glucagonlike Peptide-1 Agonist Liraglutide in Renal Transplant Recipients: A Retrospective Study. Transplant Proc 2018; 50:2502-2505. [PMID: 30316386 DOI: 10.1016/j.transproceed.2018.03.087] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Accepted: 03/02/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Diabetes mellitus (DM) is the major cause of end-stage renal disease (ESRD) in Taiwan. Despite the use of steroids and/or calcineurin inhibitors (CNIs) in renal transplantation (RTx), additional challenges occur when a patient displays persisting metabolic disease, carries on an unhealthy lifestyle, or experiences genetic effects. Although RTx recipients could get better glycemic control by oral anti-diabetic drugs (OADs) or several insulin agents, they still need more than two kinds of medication. Liraglutide, a GLP-1 receptor agonist, stimulates insulin secretion and inhibits glucagon secretion and hepatic glucose production in a glucose-dependent manner. In addition, it delays gastric emptying and suppresses appetite through the central pathways. Herein we report on the long-term benefits of liraglutide in the management of DM in RTx recipients. METHODS We retrospectively retrieved 7 RTx patients in August 2015, who had been prescribed liraglutide due to their poor glycemic control; however, 2 of them discontinued their scheduled doses within 1 month. The mean follow-up period was 19.4 ± 7.6 (range 10.5-27.6) months. RESULTS Glycemic control improved fasting blood sugar (FBS) from an initial 228.6 ± 39.1 mg/dL to a final FBS of 166.0 ± 26.6 mg/dL (P = .103), with a significant improvement in nadir glucose control (136.4 ± 5.8 mg/dL, P = .017) and with glycated hemoglobin (HbA1c) from an initial 10.0 ± 1.6% to a final 8.1 ± 0.8% (P = .043). The average body weight was from an initial of 78.0 ± 7.8 kg to a nadir of 75.1 ± 9.1 kg (P = .032). Graft renal function of the estimated glomerular filtration rate (eGFR) significantly improved from an initial 67.7 ± 18.7 to a nadir of eGFR 76.5 ± 18.7 mg/dL (P = .024). There was no significant change in urinary protein:creatinine ratio. CONCLUSION Liraglutide may be safe and effective for RTx recipients with poor diabetic glycemic control, although there have been incidences of intolerance in some patients, and potential concern regarding absorption of oral medications due to a delay of gastric emptying. Evidence of liraglutide in diabetic RTx recipients is limited, so additional prospective clinical studies should be undertaken in the future.
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Affiliation(s)
- J-H Liou
- Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Y-M Liu
- Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan
| | - C-H Chen
- Division of Basic Medical Sciences, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Life Science, Tunghai University, Taichung, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
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Cehic MG, Nundall N, Greenfield JR, Macdonald PS. Management Strategies for Posttransplant Diabetes Mellitus after Heart Transplantation: A Review. J Transplant 2018; 2018:1025893. [PMID: 29623219 PMCID: PMC5829348 DOI: 10.1155/2018/1025893] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Accepted: 12/27/2017] [Indexed: 12/23/2022] Open
Abstract
Posttransplant diabetes mellitus (PTDM) is a well-recognized complication of heart transplantation and is associated with increased morbidity and mortality. Previous studies have yielded wide ranging estimates in the incidence of PTDM due in part to variable definitions applied. In addition, there is a limited published data on the management of PTDM after heart transplantation and a paucity of studies examining the effects of newer classes of hypoglycaemic drug therapies. In this review, we discuss the role of established glucose-lowering therapies and the rationale and emerging clinical evidence that supports the role of incretin-based therapies (glucagon like peptide- (GLP-) 1 agonists and dipeptidyl peptidase- (DPP-) 4 inhibitors) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of PTDM after heart transplantation. Recently published Consensus Guidelines for the diagnosis of PTDM will hopefully lead to more consistent approaches to the diagnosis of PTDM and provide a platform for the larger-scale multicentre trials that will be needed to determine the role of these newer therapies in the management of PTDM.
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Affiliation(s)
- Matthew G. Cehic
- Faculty of Medicine, St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Heart Failure and Transplant Unit, St Vincent's Hospital, Sydney, NSW, Australia
- Victor Chang Cardiac Research Institute, Sydney, NSW, Australia
| | - Nishant Nundall
- Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, NSW, Australia
- Diabetes and Metabolism Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Jerry R. Greenfield
- Faculty of Medicine, St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, NSW, Australia
- Diabetes and Metabolism Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Peter S. Macdonald
- Faculty of Medicine, St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Heart Failure and Transplant Unit, St Vincent's Hospital, Sydney, NSW, Australia
- Victor Chang Cardiac Research Institute, Sydney, NSW, Australia
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Dubois-Laforgue D. [Post-transplantation diabetes mellitus in kidney recipients]. Nephrol Ther 2017; 13 Suppl 1:S137-S146. [PMID: 28577736 DOI: 10.1016/j.nephro.2017.01.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 01/15/2017] [Accepted: 01/17/2017] [Indexed: 10/19/2022]
Abstract
Post-transplantation diabetes mellitus is defined as diabetes that is diagnosed in grafted patients. It affects 20 to 30 % of kidney transplant recipients, with a high incidence in the first year. The increasing age at transplantation and the rising incidence of obesity may increase its prevalence in the next years. Post-transplantation diabetes mellitus is associated with poor outcomes, such as mortality, cardiovascular events or graft dysfunction. Its occurrence is mainly related to immunosuppressive agents, affecting both insulin secretion and sensibility. Immunosuppressants may be iatrogenic, and as such, induce an early and transient diabetes. They may also precociously determine a permanent diabetes, acting here as a promoting factor in patients proned to the development of type 2 diabetes. Lastly, they may behave, far from transplantation, as an additional risk factor for type 2 diabetes. The screening, management and prognosis of these different subtypes of post-transplantation diabetes mellitus will be different.
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Affiliation(s)
- Danièle Dubois-Laforgue
- Service de diabétologie, hôpital Cochin-Port Royal, 123, boulevard Port-Royal, 75014 Paris, France; Inserm U1016, institut Cochin, 22, rue Méchain, 75014 Paris, France.
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Benomar K, Espiard S, Vahe C, Le Mapihan K, Jannin A, Dharancy S, Hazzan M, Vantyghem MC. Post-transplantation diabetes: Treatment à la carte? DIABETES & METABOLISM 2016; 43:378-381. [PMID: 27840114 DOI: 10.1016/j.diabet.2016.09.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 09/28/2016] [Indexed: 01/24/2023]
Affiliation(s)
- Kanza Benomar
- Endocrinology, Diabetology and Metabolism, Lille University Hospital, 59037 Lille, France; INSERM U1190 Translational Research in Diabetes, 59037 Lille, France; E.G.I.D - FR3508 European Genomic Institute of Diabetes, 59037 Lille, France
| | - Stéphanie Espiard
- Endocrinology, Diabetology and Metabolism, Lille University Hospital, 59037 Lille, France
| | - Claire Vahe
- Endocrinology, Diabetology and Metabolism, Lille University Hospital, 59037 Lille, France
| | - Kristell Le Mapihan
- Endocrinology, Diabetology and Metabolism, Lille University Hospital, 59037 Lille, France
| | - Arnaud Jannin
- Endocrinology, Diabetology and Metabolism, Lille University Hospital, 59037 Lille, France
| | | | - Marc Hazzan
- Nephrology, Lille University Hospital, 59037 Lille, France
| | - Marie-Christine Vantyghem
- Endocrinology, Diabetology and Metabolism, Lille University Hospital, 59037 Lille, France; INSERM U1190 Translational Research in Diabetes, 59037 Lille, France; E.G.I.D - FR3508 European Genomic Institute of Diabetes, 59037 Lille, France.
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Vanhove T, Remijsen Q, Kuypers D, Gillard P. Drug-drug interactions between immunosuppressants and antidiabetic drugs in the treatment of post-transplant diabetes mellitus. Transplant Rev (Orlando) 2016; 31:69-77. [PMID: 27665059 DOI: 10.1016/j.trre.2016.09.001] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2016] [Revised: 09/01/2016] [Accepted: 09/09/2016] [Indexed: 02/06/2023]
Abstract
Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors. Currently available data, although limited, suggest that these increases are modest and, particularly with regard to gliptins and SGLT-2 inhibitors, unlikely to result in hypoglycemia. The interaction with repaglinide is more pronounced but does not preclude concomitant use if repaglinide dose is gradually titrated. Mycophenolate mofetil and azathioprine do not engage in DDIs with any antidiabetic drug. Although calcineurin inhibitors (CNIs) and mammalian target of rapamycin inhibitors (mTORi) are intrinsically prone to DDIs, their disposition is not influenced by metformin, pioglitazone, sulfonylureas (except possibly glyburide) or insulin. An effect of gliptins on the disposition of CNIs and mTORi is unlikely, but has not been definitively ruled out. Based on their disposition profiles, glyburide and canagliflozin could affect CNI and mTORi disposition although this requires further study. Finally, delayed gastric emptying as a result of glucagon-like peptide-1 agonists seems to have a limited, but not necessarily negligible effect on CNI disposition.
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Affiliation(s)
- Thomas Vanhove
- Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
| | - Quinten Remijsen
- Department of Medical Affairs, AstraZeneca BeLux, Uccle, Belgium
| | - Dirk Kuypers
- Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Pieter Gillard
- Laboratory and Clinic of Experimental Medicine and Endocrinology, KU Leuven - University of Leuven, and Department of Endocrinology, University Hospital Leuven, Leuven, Belgium
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Wallia A, Illuri V, Molitch ME. Diabetes Care After Transplant: Definitions, Risk Factors, and Clinical Management. Med Clin North Am 2016; 100:535-50. [PMID: 27095644 DOI: 10.1016/j.mcna.2016.01.005] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Patients who undergo solid organ transplantation may have preexisting diabetes mellitus (DM), develop new-onset DM after transplantation (NODAT), or have postoperative hyperglycemia that resolves shortly after surgery. Although insulin is usually used to control hyperglycemia in the hospital, following discharge most of the usual diabetes oral and parenteral medications can be used in treatment. However, when there are comorbidities such as impaired kidney or hepatic function, or heart disease, special precautions may be necessary. In addition, drug-drug interactions, such as drugs interacting with CYP3A4 enzyme pathway, require additional consideration because of possible interaction with immunosuppressive drug metabolism.
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Affiliation(s)
- Amisha Wallia
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Vidhya Illuri
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Mark E Molitch
- Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
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Sharif A, Cohney S. Post-transplantation diabetes-state of the art. Lancet Diabetes Endocrinol 2016; 4:337-49. [PMID: 26632096 DOI: 10.1016/s2213-8587(15)00387-3] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Revised: 09/28/2015] [Accepted: 10/05/2015] [Indexed: 01/14/2023]
Abstract
With increasing success in overcoming the immunological and infectious challenges accompanying solid organ transplantation, susceptibility to post-transplant diabetes and cardiovascular disease has assumed increasing importance. Although some guidance is available from diabetes-related literature pertaining to the general population, some aspects are unique to solid organ allograft recipients. Both insulin resistance and β-cell dysfunction are generally agreed to contribute to development and manifestation of post-transplant diabetes, but controversy continues about which is most important and to what extent post-transplant diabetes is a distinct entity or simply a variant of type 2 diabetes with transplant-specific components. The optimum method and timing for detection and diagnosis of post-transplant diabetes remains an area of uncertainty. However, the greatest needs are to: address the absence of contemporary data for incidence and clinical outcomes associated with post-transplant diabetes; establish the role of glycaemic control; and assess the role of new diabetic therapies in prevention and management of post-transplant diabetes. We place the present knowledge base in the context of other advances in transplantation, challenge some existing ideas, and examine the potential role of emerging diabetes therapies. In highlighting existing deficiencies, we hope to provide direction for future research that will ultimately reduce incidence and improve management of post-transplant diabetes.
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Affiliation(s)
- Adnan Sharif
- Department of Nephrology and Transplantation, Queen Elizabeth Hospital, Birmingham, UK.
| | - Solomon Cohney
- Department of Nephrology, Western & Royal Melbourne Hospitals, Melbourne, VIC, Australia
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Shivaswamy V, Boerner B, Larsen J. Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes. Endocr Rev 2016; 37:37-61. [PMID: 26650437 PMCID: PMC4740345 DOI: 10.1210/er.2015-1084] [Citation(s) in RCA: 215] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM.
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Affiliation(s)
- Vijay Shivaswamy
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
| | - Brian Boerner
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
| | - Jennifer Larsen
- Division of Diabetes, Endocrinology, and Metabolism (V.S., B.B., J.L.), Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198; and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105
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