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Pan CJ, Wang T, Yin RH, Tang XQ, Hu CH. Coronary imaging characteristics and risk factors in patients with type 2 diabetes mellitus with coronary heart disease complication. World J Diabetes 2025; 16:99151. [DOI: 10.4239/wjd.v16.i4.99151] [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: 09/12/2024] [Revised: 12/10/2024] [Accepted: 01/18/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Coronary heart disease (CHD) is a prevalent type 2 diabetes mellitus (T2DM) complication. Further, the risk stratification before angiography may help diagnose T2DM with CHD early. However, few studies have investigated the coronary imaging characteristics and risk factors of patients with T2DM complicated with CHD.
AIM To compare the differences in coronary imaging between patients with T2DM with and without CHD, determine the risk factors of T2DM complicated with CHD, and establish a predictive tool for diagnosing CHD in T2DM.
METHODS This study retrospectively analyzed 103 patients with T2DM from January 2022 to May 2024. They are categorized based on CHD occurrence into: (1) The control group, consisting of patients with T2DM without CHD; and (2) The observation group, which includes patients with T2MD with CHD. Age, sex, smoking and drinking history, CHD family history, metformin (MET) treatment pre-admission, body mass index, fasting blood glucose (FBG), triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase, aspartate aminotransferase, glycosylated hemoglobin (HbA1c), and coronary imaging data of both groups were collected from the medical record system. Logistic risk analysis was conducted to screen risk factors. The prediction model’s prediction efficiency was evaluated with receiver operating characteristic curves.
RESULTS The control and observation groups consisted of 48 and 55 cases, respectively. The two groups were statistically different in terms of age (t = 2.006, P = 0.048), FBG (t = 6.038, P = 0.000), TG (t = 2.015, P = 0.047), LDL-C (t = 2.017, P = 0.046), and BUN (t = 2.035, P = 0.044). The observation group demonstrated lower proportions of patients receiving MET (χ2 = 5.073, P = 0.024) and higher proportions of patients with HbA1c of > 7.0% (χ2 = 6.980, P = 0.008) than the control group. The observation group consisted of 15, 17, and 23 cases of moderate stenosis, severe stenosis, and occlusion, respectively, with a greater number of coronary artery occlusion cases than the control group (χ2 = 6.399, P = 0.041). The observation group consisted significantly higher number of diffuse lesion cases at 35 compared with the control group (χ2 = 15.420, P = 0.000). The observation group demonstrated a higher right coronary artery (RCA) stenosis index (t = 6.730, P = 0.000), circumflex coronary artery (LCX) stenosis index (t = 5.738, P = 0.000), and total stenosis index (t = 7.049, P = 0.000) than the control group. FBG [odds ratio (OR) = 1.472; 95% confidence interval (CI): 1.234-1.755; P = 0.000] and HbA1c (OR = 3.197; 95%CI: 1.149-8.896; P = 0.026) were independent risk factors for T2DM complicated with CHD, whereas MET (OR = 0.350; 95%CI: 0.129-0.952; P = 0.040) was considered a protective factor for CHD in T2DM.
CONCLUSION Coronary artery occlusion is a prevalent complication in patients with T2DM. Patients with T2MD with CHD demonstrated a higher degree of RCA and LCX stenosis than those with T2DM without CHD. FBG, HbA1c, and MET treatment history are risk factors for T2DM complicated with CHD.
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Affiliation(s)
- Chang-Jie Pan
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
- Department of Radiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 215006, Jiangsu Province, China
| | - Tao Wang
- Department of Radiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 215006, Jiangsu Province, China
| | - Ruo-Han Yin
- Department of Radiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 215006, Jiangsu Province, China
| | - Xiao-Qiang Tang
- Department of Radiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 215006, Jiangsu Province, China
| | - Chun-Hong Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
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Solini A, Tricò D. Clinical efficacy and cost-effectiveness of metformin in different patient populations: A narrative review of real-world evidence. Diabetes Obes Metab 2024; 26 Suppl 3:20-30. [PMID: 38939954 DOI: 10.1111/dom.15729] [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: 04/17/2024] [Revised: 06/03/2024] [Accepted: 06/03/2024] [Indexed: 06/29/2024]
Abstract
Over the past two decades, diabetes pharmacopoeia has flourished, with new drugs that, on top of their glucose-lowering efficacy, have been shown to protect the heart and the kidney. Despite these new opportunities, metformin retains a pivotal role among glucose-lowering agents. As one of the few available insulin sensitizers, metformin is an effective, safe, and overall well-tolerated drug backed by over 60 years of clinical experience, including evidence for potential benefits beyond glucose reduction across different ages, sexes, genetic backgrounds, geographical areas, and stages of disease. Although there is some discussion of whether metformin offers the most effective front-line option in newly diagnosed type 2 diabetes (T2D), it remains a natural companion to all other glucose-lowering agents. Furthermore, metformin comes at a very low cost and, as such, it has extremely high cost-effectiveness, particularly given the serious economic burden associated with diabetes complications. This financial advantage is particularly relevant in resource-constrained healthcare systems, where the affordability of metformin may be instrumental in implementing an effective treatment in an evergrowing number of individuals. We present here compelling real-world evidence in support of the clinical efficacy and cost-effectiveness of metformin across different patient populations, highlighting areas where more population-based studies are needed to further incorporate and consolidate its use in the pharmacological management of T2D.
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Affiliation(s)
- Anna Solini
- Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy
| | - Domenico Tricò
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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Wong HJ, Lin NH, Teo YN, Syn NL, Teo YH, Sia CH. Evaluation of the Lifetime Benefits of Metformin and SGLT2 Inhibitors in Type 2 Diabetes Mellitus Patients with Cardiovascular Disease: A Systematic Review and Two-Stage Meta-Analysis. Am J Cardiovasc Drugs 2024; 24:371-383. [PMID: 38589722 DOI: 10.1007/s40256-024-00640-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/11/2024] [Indexed: 04/10/2024]
Abstract
BACKGROUND Metformin and sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardiovascular benefits but their comparative effects on mortality in type 2 diabetes mellitus (T2DM) patients with cardiovascular disease (CVD) are unknown. Hence, we evaluated and compared lifetime benefits arising from metformin or SGLT2 inhibitors in T2DM patients with CVD. MATERIALS AND METHODS Studies published in the PubMed, EMBASE and CENTRAL databases before 28 October 2023 were retrieved. Treatment effects of metformin against US FDA-approved SGLT2 inhibitors in T2DM patients with CVD were evaluated and lifetime gains in event-free survival were estimated from our primary endpoints of all-cause and cardiovascular mortality. Risk ratios were derived to assess their impact on secondary outcomes such as major adverse cardiovascular events and hospitalizations for heart failure. RESULTS Overall, 14 studies were included. Five studies published Kaplan-Meier curves for the primary outcome of all-cause mortality. Individual participant data were reconstructed from these Kaplan-Meier curves, from which we conducted our two-stage meta-analysis. Participants receiving metformin and SGLT2 inhibitors experienced a reduction in the risk for all-cause mortality as compared with those not taking metformin and placebo. However, participants receiving SGLT2 inhibitors had a higher all-cause mortality (hazard ratio 1.308, 95% confidence interval 1.103-1.550) versus metformin. Treatment with metformin was estimated to offer an additional 23.26 months of survival free from all-cause mortality versus 23.04 months with SGLT2 inhibitors. CONCLUSIONS In patients with T2DM and CVD, metformin and SGLT2 inhibitors were associated with substantially lower all-cause mortality rates and slightly longer life expectancies than in patients without. Metformin presented an advantage over SGLT2 inhibitors in reducing all-cause mortality.
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Affiliation(s)
- Hon Jen Wong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Norman H Lin
- Department of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, Singapore, 119228, Singapore
| | - Yao Neng Teo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Nicholas L Syn
- Department of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, Singapore, 119228, Singapore
| | - Yao Hao Teo
- Department of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, Singapore, 119228, Singapore
| | - Ching-Hui Sia
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Department of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, Singapore, 119228, Singapore.
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Lopez-Candales A, Monte S, Sawalha K, Norgard NB. Time to revisit the true role of metformin in type 2 diabetes mellitus. Postgrad Med 2023; 135:539-542. [PMID: 37294638 DOI: 10.1080/00325481.2023.2224036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 06/06/2023] [Indexed: 06/11/2023]
Affiliation(s)
- Angel Lopez-Candales
- Cardiovascular Medicine Division, University Health Truman Medical Center, University of Missouri-Kansas City, Missouri-Kansas, MO, USA
| | - Scott Monte
- School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, NY, USA
| | - Khalid Sawalha
- Nutrition and Metabolism, Department of Medicine, University of Missouri-Kansas City, Kansas, MO, USA
| | - Nicholas B Norgard
- Department of Medicine, University Health Truman Medical Center, University of Missouri-Kansas City, Kansas, MO, USA
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Коротина МА, Починка ИГ, Стронгин ЛГ. [Use of metformin in patients with type 2 diabetes and acute myocardial infarction: safety and impact on glycemic control]. PROBLEMY ENDOKRINOLOGII 2023; 69:28-35. [PMID: 36842075 PMCID: PMC9978873 DOI: 10.14341/probl13170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 10/05/2022] [Indexed: 02/27/2023]
Abstract
BACKGROUND Myocardial infarction (MI) in patients with diabetes type 2 (T2DM) occurs 1.5-3.0 times higher than in general population. Metformin is contraindicated for patients with T2DM and acute coronary syndrome due to the risk of developing lactic acidosis. Using metformin more than 48 hours of MI is a topical question, which will help to improve patient's safety. AIM To evaluate the safety and quality of glycemic control using metformin in patients with T2DM during inpatient treatment for MIMATERIALS AND METHODS: The study included 161 patients with T2DM, who were hospitalized consecutively with acute MI with ST-elevation and underwent percutaneous coronary intervention (PCI). Average time of metformin initiation was 5th day from admission. Creatinine was assessed at admission and 48 hours after PCI. The acid-base balance and lactate were assessed at admission and on the 3rd day after the start of using metformin. Criteria for the effectiveness of glycemic control was the proportion of glycemic measurements in target range of 6.1-10.0 mmol/l during hospitalization ("hospital time in range", hTIR). hTIR >55% was considered to be a critical level. The long-term outcome was estimated at 365 days after hospitalization. RESULTS Metformin was prescribed to 99 patients (61%) ("M+"group) during the hospitalization, 62 patients were in "M-"group. Use of metformin was accompanied with better glycemic control in the «M+» group compared to the «M-»: mean glycemia 9.3 ± 1.6 vs 10.3 ± 2.3 mmol/l (p=0,002), SD 2.87 ± 1.1 vs 3.26 ± 1.8 (p=0,049), hTIR 60 ± 18% vs 48 ± 23% (p<0,001). There were clinically insignificant changes in acid-base balance on the 3rd day from the start of metformin use in the "M+" group, the lactate level did not increase. Use of metformin before to hospitalization with MI was not associated with an increased risk of developing acute kidney injury (AKI): RR 0.85 (0.37-1.96), p=0,691. CONCLUSION Use of metformin in patients with T2DM and acute MI is associated with better glycemic control. Carrying out angiography in patients, treated with metformin before the hospitalization, is not accompanied by an increased risk of developing AKI. Appointment of metformin in 3-7 days after angiography does not lead to an increase level of lactate and significant deviations in acid-base balance.
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Affiliation(s)
| | - И. Г. Починка
- Приволжский исследовательский медицинский университет
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Xu Z, Zhang H, Wu C, Zheng Y, Jiang J. Effect of metformin on adverse outcomes in T2DM patients: Systemic review and meta-analysis of observational studies. Front Cardiovasc Med 2022; 9:944902. [PMID: 36211585 PMCID: PMC9539433 DOI: 10.3389/fcvm.2022.944902] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/08/2022] [Indexed: 11/15/2022] Open
Abstract
Background The cardiovascular protection effect of metformin on patients with type 2 diabetes mellitus (T2DM) remains inconclusive. This systemic review and meta-analysis were to estimate the effect of metformin on mortality and cardiovascular events among patients with T2DM. Methods A search of the Pubmed and EMBASE databases up to December 2021 was performed. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled by a random-effects model with an inverse variance method. Results A total of 39 studies involving 2473009 T2DM patients were adopted. Compared to non-metformin therapy, the use of metformin was not significantly associated with a reduced risk of major adverse cardiovascular event (MACE) (HR = 1.06, 95%CI 0.91–1.22; I2 = 82%), hospitalization (HR = 0.85, 95%CI 0.64–1.13; I2 = 98%), heart failure (HR = 0.86, 95%CI 0.60–1.25; I2 = 99%), stroke (HR = 1.16, 95%CI 0.88–1.53; I2 = 84%), and risk of AMI (HR = 0.88, 95%CI 0.69–1.14; I2 = 88%) in T2DM patients. Metformin was also not associated with significantly lowered risk of MACE compared to dipeptidyl peptidase-4 inhibitor (DPP-4i) in T2DM patients (HR = 0.95, 95%CI 0.73–1.23; I2 = 84%). Conclusions The effect of metformin on some cardiovascular outcomes was not significantly better than the non-metformin therapy or DPP-4i in T2DM patients based on observational studies.
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Affiliation(s)
- Zhicheng Xu
- Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- *Correspondence: Zhicheng Xu
| | - Haidong Zhang
- Department of Nephrology, Peking University Third Hospital, Bejing, China
- Haidong Zhang
| | - Chenghui Wu
- School of Medicine, Sun Yat-sen University, Shenzhen, China
| | - Yuxiang Zheng
- Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingzhou Jiang
- Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Jingzhou Jiang
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Triggle CR, Mohammed I, Bshesh K, Marei I, Ye K, Ding H, MacDonald R, Hollenberg MD, Hill MA. Metformin: Is it a drug for all reasons and diseases? Metabolism 2022; 133:155223. [PMID: 35640743 DOI: 10.1016/j.metabol.2022.155223] [Citation(s) in RCA: 130] [Impact Index Per Article: 43.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 05/22/2022] [Accepted: 05/25/2022] [Indexed: 12/15/2022]
Abstract
Metformin was first used to treat type 2 diabetes in the late 1950s and in 2022 remains the first-choice drug used daily by approximately 150 million people. An accumulation of positive pre-clinical and clinical data has stimulated interest in re-purposing metformin to treat a variety of diseases including COVID-19. In polycystic ovary syndrome metformin improves insulin sensitivity. In type 1 diabetes metformin may help reduce the insulin dose. Meta-analysis and data from pre-clinical and clinical studies link metformin to a reduction in the incidence of cancer. Clinical trials, including MILES (Metformin In Longevity Study), and TAME (Targeting Aging with Metformin), have been designed to determine if metformin can offset aging and extend lifespan. Pre-clinical and clinical data suggest that metformin, via suppression of pro-inflammatory pathways, protection of mitochondria and vascular function, and direct actions on neuronal stem cells, may protect against neurodegenerative diseases. Metformin has also been studied for its anti-bacterial, -viral, -malaria efficacy. Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an anti-hyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct anti-viral actions. Clarification is also sought as to whether data from ex vivo studies based on the use of high concentrations of metformin can be translated into clinical benefits, or whether they reflect a 'Paracelsus' effect. The environmental impact of metformin, a drug with no known metabolites, is another emerging issue that has been linked to endocrine disruption in fish, and extensive use in T2D has also raised concerns over effects on human reproduction. The objectives for this review are to: 1) evaluate the putative mechanism(s) of action of metformin; 2) analyze the controversial evidence for metformin's effectiveness in the treatment of diseases other than type 2 diabetes; 3) assess the reproducibility of the data, and finally 4) reach an informed conclusion as to whether metformin is a drug for all diseases and reasons. We conclude that the primary clinical benefits of metformin result from its insulin-sensitizing and antihyperglycaemic effects that secondarily contribute to a reduced risk of a number of diseases and thereby enhancing healthspan. However, benefits like improving vascular endothelial function that are independent of effects on glucose homeostasis add to metformin's therapeutic actions.
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Affiliation(s)
- Chris R Triggle
- Department of Pharmacology, Weill Cornell Medicine in Qatar, P.O. Box 24144, Education City, Doha, Qatar; Department of Medical Education, Weill Cornell Medicine in Qatar, P.O. Box 24144, Education City, Doha, Qatar.
| | - Ibrahim Mohammed
- Department of Medical Education, Weill Cornell Medicine in Qatar, P.O. Box 24144, Education City, Doha, Qatar
| | - Khalifa Bshesh
- Department of Medical Education, Weill Cornell Medicine in Qatar, P.O. Box 24144, Education City, Doha, Qatar
| | - Isra Marei
- Department of Pharmacology, Weill Cornell Medicine in Qatar, P.O. Box 24144, Education City, Doha, Qatar
| | - Kevin Ye
- Department of Biomedical Physiology & Kinesiology, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada
| | - Hong Ding
- Department of Pharmacology, Weill Cornell Medicine in Qatar, P.O. Box 24144, Education City, Doha, Qatar; Department of Medical Education, Weill Cornell Medicine in Qatar, P.O. Box 24144, Education City, Doha, Qatar
| | - Ross MacDonald
- Distribution eLibrary, Weill Cornell Medicine in Qatar, P.O. Box 24144, Education City, Doha, Qatar
| | - Morley D Hollenberg
- Department of Physiology & Pharmacology, a Cumming School of Medicine, University of Calgary, T2N 4N1, Canada
| | - Michael A Hill
- Dalton Cardiovascular Research Center, Department of Medical Pharmacology & Physiology, School of Medicine, University of Missouri, Columbia 65211, MO, USA
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Wiernsperger N, Al-Salameh A, Cariou B, Lalau JD. Protection by metformin against severe Covid-19: an in-depth mechanistic analysis. DIABETES & METABOLISM 2022; 48:101359. [PMID: 35662580 PMCID: PMC9154087 DOI: 10.1016/j.diabet.2022.101359] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 05/25/2022] [Accepted: 05/25/2022] [Indexed: 12/05/2022]
Abstract
Since the outbreak of Covid-19, several observational studies on diabetes and Covid-19 have reported a favourable association between metformin and Covid-19-related outcomes in patients with type 2 diabetes mellitus (T2DM). This is not surprising since metformin affects many of the pathophysiological mechanisms implicated in SARS-CoV-2 immune response, systemic spread and sequelae. A comparison of the multifactorial pathophysiological mechanisms of Covid-19 progression with metformin's well-known pleiotropic properties suggests that the treatment of patients with this drug might be particularly beneficial. Indeed, metformin could alleviate the cytokine storm, diminish virus entry into cells, protect against microvascular damage as well as prevent secondary fibrosis. Although our in-depth analysis covers many potential metformin mechanisms of action, we want to highlight more particularly its unique microcirculatory protective effects since worsening of Covid-19 disease clearly appears as largely due to severe defects in the structure and functioning of microvessels. Overall, these observations confirm that metformin is a unique, pleiotropic drug that targets many of Covid-19′s pathophysiology processes in a diabetes-independent manner.
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Affiliation(s)
| | - Abdallah Al-Salameh
- Department of Endocrinology, Diabetes Mellitus and Nutrition, Amiens University Hospital, Amiens, France; PériTox/UMR-I 01, University of Picardie Jules Verne, Amiens, France
| | - Bertrand Cariou
- Département d'Endocrinologie, Diabétologie et Nutrition, l'institut du thorax, Inserm, CNRS, UNIV Nantes, CHU Nantes, Hôpital Guillaume et René Laennec, 44093 Nantes Cedex 01, France
| | - Jean-Daniel Lalau
- Department of Endocrinology, Diabetes Mellitus and Nutrition, Amiens University Hospital, Amiens, France; PériTox/UMR-I 01, University of Picardie Jules Verne, Amiens, France.
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The Impact of Hypoglycemic Therapy on the Prognosis for Acute Coronary Syndrome in Patients with Type 2 Diabetes. J Pers Med 2022; 12:jpm12050845. [PMID: 35629267 PMCID: PMC9143707 DOI: 10.3390/jpm12050845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 05/12/2022] [Accepted: 05/18/2022] [Indexed: 02/01/2023] Open
Abstract
The article discusses particular circumstances of acute coronary syndrome (ACS) in patients with type 2 diabetes (T2D). In addition, the available literature data and clinical guidelines reflecting the role of hypoglycemic therapy as a cardioprotection factor in ACS are analyzed. The article considers possible protective molecular mechanisms of various groups of drugs in ischemic cardiomyocytes.
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Kulkarni AS, Aleksic S, Berger DM, Sierra F, Kuchel G, Barzilai N. Geroscience-guided repurposing of FDA-approved drugs to target aging: A proposed process and prioritization. Aging Cell 2022; 21:e13596. [PMID: 35343051 PMCID: PMC9009114 DOI: 10.1111/acel.13596] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 02/11/2022] [Accepted: 03/13/2022] [Indexed: 12/29/2022] Open
Abstract
Common chronic diseases represent the greatest driver of rising healthcare costs, as well as declining function, independence, and quality of life. Geroscience-guided approaches seek to delay the onset and progression of multiple chronic conditions by targeting fundamental biological pathways of aging. This approach is more likely to improve overall health and function in old age than treating individual diseases, by addressing aging the largest and mostly ignored risk factor for the leading causes of morbidity in older adults. Nevertheless, challenges in repurposing existing and moving newly discovered interventions from the bench to clinical care have impeded the progress of this potentially transformational paradigm shift. In this article, we propose the creation of a standardized process for evaluating FDA-approved medications for their geroscience potential. Criteria for systematically evaluating the existing literature that spans from animal models to human studies will permit the prioritization of efforts and financial investments for translating geroscience and allow immediate progress on the design of the next Targeting Aging with MEtformin (TAME)-like study involving such candidate gerotherapeutics.
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Affiliation(s)
- Ameya S. Kulkarni
- Institute for Aging ResearchAlbert Einstein College of MedicineBronxNew YorkUSA
- Present address:
AbbVie Inc.North ChicagoIL60064USA.
| | - Sandra Aleksic
- Department of Medicine (Endocrinology and Geriatrics)Albert Einstein College of MedicineBronxNew YorkUSA
| | - David M. Berger
- Department of Medicine (Hospital Medicine)Montefiore Medical Center and Albert Einstein College of MedicineBronxNew YorkUSA
| | - Felipe Sierra
- Centre Hospitalier Universitaire de ToulouseToulouseFrance
| | - George A. Kuchel
- UConn Center on AgingUniversity of Connecticut School of MedicineFarmingtonConnecticutUSA
| | - Nir Barzilai
- Institute for Aging ResearchAlbert Einstein College of MedicineBronxNew YorkUSA
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Ferri-Guerra J, Aparicio-Ugarriza R, Mohammed YN, Ysea O, Florez H, Ruiz JG. Propensity Score Matching to Determine the Impact of Metformin on All-Cause Mortality in Older Veterans with Diabetes Mellitus. South Med J 2022; 115:208-213. [PMID: 35237840 DOI: 10.14423/smj.0000000000001363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVES To determine whether metformin is associated with reduced all-cause mortality in older adults with diabetes mellitus as compared with insulin or sulfonylureas, and to evaluate whether the metformin cumulative exposure followed a dose-response relation. METHODS Retrospective cohort study with propensity score matching in veterans 65 years old and older with diabetes mellitus. Patients who had new prescriptions for metformin were matched for demographic and clinical factors with patients receiving new prescriptions for insulin or sulfonylureas using propensity score matching. All-cause mortality risks were compared between metformin and insulin/sulfonylureas using multivariate Cox regression models. A similar approach was used for tertiles of cumulative metformin doses. RESULTS A sample of 174 veterans taking metformin was matched with 174 who took insulin/sulfonylureas. Most patients were men (97.4%), White (80.45%), and their mean ± standard deviation age was 69.15 ± 7.65 years. Metformin exposure was associated with reduced risk of all-cause mortality (hazard ratio 0.57, 95% confidence interval 0.39-0.84, P = 0.005). The upper tertile of cumulative metformin exposure was associated with lower all-cause mortality in the fully adjusted model (hazard ratio 0.28, 95% confidence interval 0.10-0.77, P = 0.013). CONCLUSIONS This propensity matching study shows that metformin exposure is associated with a lower risk of all-cause mortality. Higher metformin cumulative exposure seems to reduce the risk of all-cause mortality in older veterans with diabetes mellitus.
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Affiliation(s)
- Juliana Ferri-Guerra
- From the Miami VA Healthcare System Geriatric Research, Education, and Clinical Center (GRECC), Miami, Florida
| | - Raquel Aparicio-Ugarriza
- From the Miami VA Healthcare System Geriatric Research, Education, and Clinical Center (GRECC), Miami, Florida
| | - Y Nadeem Mohammed
- From the Miami VA Healthcare System Geriatric Research, Education, and Clinical Center (GRECC), Miami, Florida
| | - Otoniel Ysea
- From the Miami VA Healthcare System Geriatric Research, Education, and Clinical Center (GRECC), Miami, Florida
| | - Hermes Florez
- From the Miami VA Healthcare System Geriatric Research, Education, and Clinical Center (GRECC), Miami, Florida
| | - Jorge G Ruiz
- From the Miami VA Healthcare System Geriatric Research, Education, and Clinical Center (GRECC), Miami, Florida
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Li T, Providencia R, Jiang W, Liu M, Yu L, Gu C, Chang ACY, Ma H. Association of Metformin with the Mortality and Incidence of Cardiovascular Events in Patients with Pre-existing Cardiovascular Diseases. Drugs 2022; 82:311-322. [PMID: 35032305 DOI: 10.1007/s40265-021-01665-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2021] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Whether metformin reduces all-cause cardiovascular mortality and the incidence of cardiovascular events in patients with pre-existing cardiovascular diseases (CVD) remains inconclusive. Some randomised controlled trials (RCTs) and cohort studies have shown that metformin is associated with an increased risk of mortality and cardiovascular events. METHODS We conducted a pooling synthesis to assess the effects of metformin in all-cause cardiovascular mortality and incidence of cardiovascular events in patients with CVD. Studies published up to October 2021 in PubMed or Embase with a registration in PROSPERO (CRD42020189905) were collected. Both RCT and cohort studies were included. Hazard ratios (HR) with 95% CI were pooled across various trials using the random-effects model. RESULTS This study enrolled 35 published studies (in 14 publications) for qualitative synthesis and identified 33 studies (published in 26 publications) for quantitative analysis. We analysed a total of 61,704 patients, among them 58,271 patients were used to calculate all-cause mortality while 12,814 patients were used to calculate cardiovascular mortality. Compared with non-metformin control, metformin usage is associated with a reduction in all-cause mortality (HR: 0.90; 95% CI 0.83, 0.98; p = 0.01), cardiovascular mortality (HR: 0.89; 95% CI 0.85, 0.94; p < 0.0001), incidence of coronary revascularisation (HR: 0.79; 95% CI 0.64, 0.98; p = 0.03), and heart failure (HR: 0.90; 95% CI 0.87, 0.94; p < 0.0001) in patients with pre-existing cardiovascular diseases. CONCLUSION Metformin use is associated with a reduction in all-cause mortality, cardiovascular mortality, incidence of coronary revascularisation, and heart failure in patients with CVD; however, metformin usage was not associated with reduction in the incidence of myocardial infarction, angina, or stroke.
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Affiliation(s)
- Tian Li
- Department of Physiology and Pathophysiology, Fourth Military Medical University, No. 169 Changle West Rd, Xi'an, 710032, China
| | | | - Wenhua Jiang
- Department of Physiology and Pathophysiology, Fourth Military Medical University, No. 169 Changle West Rd, Xi'an, 710032, China
| | - Manling Liu
- Department of Physiology and Pathophysiology, Fourth Military Medical University, No. 169 Changle West Rd, Xi'an, 710032, China
| | - Lu Yu
- Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Chunhu Gu
- Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Alex Chia Yu Chang
- Department of Cardiology and Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 211125, China.
| | - Heng Ma
- Department of Physiology and Pathophysiology, Fourth Military Medical University, No. 169 Changle West Rd, Xi'an, 710032, China.
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13
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Ahmad E, Sargeant JA, Zaccardi F, Khunti K, Webb DR, Davies MJ. Where Does Metformin Stand in Modern Day Management of Type 2 Diabetes? Pharmaceuticals (Basel) 2020; 13:E427. [PMID: 33261058 PMCID: PMC7761522 DOI: 10.3390/ph13120427] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 11/24/2020] [Accepted: 11/25/2020] [Indexed: 02/06/2023] Open
Abstract
Metformin is the most commonly used glucose-lowering therapy (GLT) worldwide and remains the first-line therapy for newly diagnosed individuals with type 2 diabetes (T2D) in management algorithms and guidelines after the UK Prospective Diabetes Study (UKPDS) showed cardiovascular mortality benefits in the overweight population using metformin. However, the improved Major Adverse Cardiovascular Events (MACE) realised in some of the recent large cardiovascular outcomes trials (CVOTs) using sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have challenged metformin's position as a first-line agent in the management of T2D. Many experts now advocate revising the existing treatment algorithms to target atherosclerotic cardiovascular disease (ASCVD) and improving glycaemic control as a secondary aim. In this review article, we will revisit the major cardiovascular outcome data for metformin and include a critique of the UKPDS data. We then review additional factors that might be pertinent to metformin's status as a first-line agent and finally answer key questions when considering metformin's role in the modern-day management of T2D.
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Affiliation(s)
- Ehtasham Ahmad
- Diabetes Research Centre, University of Leicester, Leicester LE5 4PW, UK; (J.A.S.); (F.Z.); (K.K.); (D.R.W.); (M.J.D.)
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester LE5 4PW, UK
| | - Jack A. Sargeant
- Diabetes Research Centre, University of Leicester, Leicester LE5 4PW, UK; (J.A.S.); (F.Z.); (K.K.); (D.R.W.); (M.J.D.)
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester LE5 4PW, UK
| | - Francesco Zaccardi
- Diabetes Research Centre, University of Leicester, Leicester LE5 4PW, UK; (J.A.S.); (F.Z.); (K.K.); (D.R.W.); (M.J.D.)
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester LE5 4PW, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester LE5 4PW, UK; (J.A.S.); (F.Z.); (K.K.); (D.R.W.); (M.J.D.)
- NIHR Applied Research Collaborations (ARC), East Midlands, Leicester LE5 4PW, UK
| | - David R. Webb
- Diabetes Research Centre, University of Leicester, Leicester LE5 4PW, UK; (J.A.S.); (F.Z.); (K.K.); (D.R.W.); (M.J.D.)
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester LE5 4PW, UK
| | - Melanie J. Davies
- Diabetes Research Centre, University of Leicester, Leicester LE5 4PW, UK; (J.A.S.); (F.Z.); (K.K.); (D.R.W.); (M.J.D.)
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester LE5 4PW, UK
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14
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Halabi A, Sen J, Huynh Q, Marwick TH. Metformin treatment in heart failure with preserved ejection fraction: a systematic review and meta-regression analysis. Cardiovasc Diabetol 2020; 19:124. [PMID: 32758236 PMCID: PMC7409497 DOI: 10.1186/s12933-020-01100-w] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 07/25/2020] [Indexed: 12/23/2022] Open
Abstract
Background Observational series suggest a mortality benefit from metformin in the heart failure (HF) population. However, the benefit of metformin in HF with preserved ejection fraction (HFpEF) has yet to be explored. We performed a systematic review and meta-analysis to identify whether variation in EF impacts mortality outcomes in HF patients treated with metformin. Methods MEDLINE and EMBASE were searched up to October 2019. Observational studies and randomised trials reporting mortality in HF patients and the proportion of patients with an EF > 50% at baseline were included. Other baseline variables were used to assess for heterogeneity in treatment outcomes between groups. Regression models were used to determine the interaction between metformin and subgroups on mortality. Results Four studies reported the proportion of patients with a preserved EF and were analysed. Metformin reduced mortality in both preserved or reduced EF after adjustment with HF therapies such as angiotensin converting enzyme inhibitors (ACEi) and beta-blockers (β = − 0.2 [95% CI − 0.3 to − 0.1], p = 0.02). Significantly greater protective effects were seen with EF > 50% (p = 0.003). Metformin treatment with insulin, ACEi and beta-blocker therapy were also shown to have a reduction in mortality (insulin p = 0.002; ACEi p < 0.001; beta-blocker p = 0.017), whereas female gender was associated with worse outcomes (p < 0.001). Conclusions Metformin treatment is associated with a reduction in mortality in patients with HFpEF.
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Affiliation(s)
- Amera Halabi
- (Dept) Imaging Research, Baker Heart and Diabetes Institute, PO Box 6492, 75 Commercial Road, Melbourne, VIC, 3004, Australia.,School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia
| | - Jonathan Sen
- (Dept) Imaging Research, Baker Heart and Diabetes Institute, PO Box 6492, 75 Commercial Road, Melbourne, VIC, 3004, Australia.,Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, 207 Bouverie Street, Parkville, VIC, 3010, Australia
| | - Quan Huynh
- (Dept) Imaging Research, Baker Heart and Diabetes Institute, PO Box 6492, 75 Commercial Road, Melbourne, VIC, 3004, Australia.,School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia
| | - Thomas H Marwick
- (Dept) Imaging Research, Baker Heart and Diabetes Institute, PO Box 6492, 75 Commercial Road, Melbourne, VIC, 3004, Australia. .,School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia. .,(Dept) Imaging Research, Menzies Institute for Medical Research, 17 Liverpool Street, Hobart, TAS, 7000, Australia.
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15
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Chiang CE, Ueng KC, Chao TH, Lin TH, Wu YJ, Wang KL, Sung SH, Yeh HI, Li YH, Liu PY, Chang KC, Shyu KG, Huang JL, Tsai CD, Hung HF, Liu ME, Chao TF, Cheng SM, Cheng HM, Chu PH, Yin WH, Wu YW, Chen WJ, Lai WT, Lin SJ, Yeh SJ, Hwang JJ. 2020 Consensus of Taiwan Society of Cardiology on the pharmacological management of patients with type 2 diabetes and cardiovascular diseases. J Chin Med Assoc 2020; 83:587-621. [PMID: 32628427 DOI: 10.1097/jcma.0000000000000359] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
The global incidence and prevalence of type 2 diabetes have been escalating in recent decades. The total diabetic population is expected to increase from 415 million in 2015 to 642 million by 2040. Patients with type 2 diabetes have an increased risk of atherosclerotic cardiovascular disease (ASCVD). About two-thirds of patients with type 2 diabetes died of ASCVD. The association between hyperglycemia and elevated cardiovascular (CV) risk has been demonstrated in multiple cohort studies. However, clinical trials of intensive glucose reduction by conventional antidiabetic agents did not significantly reduce macrovascular outcomes.In December 2008, U.S. Food and Drug Administration issued a mandate that every new antidiabetic agent requires rigorous assessments of its CV safety. Thereafter, more than 200,000 patients have been enrolled in a number of randomized controlled trials (RCTs). These trials were initially designed to prove noninferiority. It turned out that some of these trials demonstrated superiority of some new antidiabetic agents versus placebo in reducing CV endpoints, including macrovascular events, renal events, and heart failure. These results are important in clinical practice and also provide an opportunity for academic society to formulate treatment guidelines or consensus to provide specific recommendations for glucose control in various CV diseases.In 2018, the Taiwan Society of Cardiology (TSOC) and the Diabetes Association of Republic of China (DAROC) published the first joint consensus on the "Pharmacological Management of Patients with Type 2 Diabetes and Cardiovascular Diseases." In 2020, TSOC appointed a new consensus group to revise the previous version. The updated 2020 consensus was comprised of 5 major parts: (1) treatment of diabetes in patients with multiple risk factors, (2) treatment of diabetes in patients with coronary heart disease, (3) treatment of diabetes in patients with stage 3 chronic kidney disease, (4) treatment of diabetes in patients with a history of stroke, and (5) treatment of diabetes in patients with heart failure. The members of the consensus group thoroughly reviewed all the evidence, mainly RCTs, and also included meta-analyses and real-world evidence. The treatment targets of HbA1c were finalized. The antidiabetic agents were ranked according to their clinical evidence. The consensus is not mandatory. The final decision may need to be individualized and based on clinicians' discretion.
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Affiliation(s)
- Chern-En Chiang
- General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Kwo-Chang Ueng
- Chung-Shan Medical University Hospital, Taichung, Taiwan, ROC
| | - Ting-Hsing Chao
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Tsung-Hsien Lin
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Yih-Jer Wu
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan, ROC
- Cardiovascular Center, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan, ROC
| | - Kang-Ling Wang
- General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Shih-Hsien Sung
- Department of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Hung-I Yeh
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan, ROC
- Cardiovascular Center, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan, ROC
| | - Yi-Heng Li
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Ping-Yen Liu
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Kuan-Cheng Chang
- Division of Cardiovascular Medicine, China Medical University Hospital, Taichung, Taiwan, ROC
- School of Medicine, China Medical University, Taichung, Taiwan, ROC
| | - Kou-Gi Shyu
- Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC
| | - Jin-Long Huang
- Cardiovascular center, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
| | - Cheng-Dao Tsai
- Department of Medicine, Changhua Christian Hospital, Changhua, Taiwan, ROC
| | - Huei-Fong Hung
- Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC
| | - Ming-En Liu
- Division of Cardiology, Department of Internal Medicine, Hsinchu Mackay Memorial Hospital, Hsinchu, Taiwan, ROC
| | - Tze-Fan Chao
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Institute of Clinical Medicine, and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Shu-Meng Cheng
- Division of Cardiology, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan, ROC
| | - Hao-Min Cheng
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Institute of Public Health, National Yang-Ming University, Taipei, Taiwan, ROC
- Institute of Health and Welfare Policy, National Yang-Ming University, Taipei, Taiwan, ROC
- Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
| | - Pao-Hsien Chu
- Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
- School of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Wei-Hsian Yin
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Heart Center, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Yen-Wen Wu
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Cardiology, Cardiovascular Medical Center, and Department of Nuclear, ROC Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan, ROC
- Department of Internal Medicine and Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC
| | - Wen-Jone Chen
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC
| | - Wen-Ter Lai
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Shing-Jong Lin
- Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan, ROC
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - San-Jou Yeh
- Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
| | - Juey-Jen Hwang
- Cardiovascular Division, Department of Internal Medicine, National Taiwan, ROC, University College of Medicine and Hospital, Taipei, Taiwan, ROC
- Cardiovascular Center, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan, ROC
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16
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Bergmark BA, Bhatt DL, McGuire DK, Cahn A, Mosenzon O, Steg PG, Im K, Kanevsky E, Gurmu Y, Raz I, Braunwald E, Scirica BM. Metformin Use and Clinical Outcomes Among Patients With Diabetes Mellitus With or Without Heart Failure or Kidney Dysfunction. Circulation 2019; 140:1004-1014. [DOI: 10.1161/circulationaha.119.040144] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background:
Metformin is first-line therapy for type 2 diabetes mellitus, although its effects on the cardiovascular system are unproved.
Methods:
In this post hoc analysis, patients in SAVOR-TIMI 53 (Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus) with baseline biomarker samples (n=12 156) were classified as ever versus never taking metformin during the trial period. Associations between metformin exposure and outcomes were estimated with inverse probability of treatment weighting Cox modeling for the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke, as well as cardiovascular death and all-cause mortality, with biomarkers included as covariates. Additional sensitivity analyses included propensity score matching and Cox multivariable models.
Results:
Of the 12 156 patients with baseline biomarker samples, 8971 (74%) had metformin exposure, 1611 (13%) had prior heart failure, and 1332 (11%) had at least moderate chronic kidney disease (estimated glomerular filtration rate ≤45 mL·min
−1
·1.73 m
−2
). Metformin use was associated with no difference in risk for the composite end point (hazard ratio for inverse probability of treatment weighting, 0.92 [95% CI, 0.76–1.11]) but lower risk of all-cause mortality (hazard ratio for inverse probability of treatment weighting, 0.75 [95% CI, 0.59–0.95]). There was no significant relationship between metformin use and these end points in patients with prior heart failure or moderate to severe chronic kidney disease.
Conclusions:
In a cohort of 12 156 patients with type 2 diabetes mellitus and high cardiovascular risk, metformin use was associated with lower rates of all-cause mortality, including after adjustment for clinical variables and biomarkers, but not lower rates of the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. This association was most apparent in patients without prior heart failure or moderate to severe chronic kidney disease.
Clinical Trial Registration:
URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01107886.
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Affiliation(s)
- Brian A. Bergmark
- Thrombolysis in Myocardial Infarction (TIMI) Study Group (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- Cardiovascular Division, Heart and Vascular Center (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Deepak L. Bhatt
- Thrombolysis in Myocardial Infarction (TIMI) Study Group (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- Cardiovascular Division, Heart and Vascular Center (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Darren K. McGuire
- Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (D.K.M.)
| | - Avivit Cahn
- Diabetes Unit, Division of Internal Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Israel (A.C., O.M., I.R.)
| | - Ofri Mosenzon
- Diabetes Unit, Division of Internal Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Israel (A.C., O.M., I.R.)
| | - Ph. Gabriel Steg
- FACT (French Alliance for Cardiovascular Clinical Trials), Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation, Remodelling), Université de Paris, Sorbonne Paris-Cité, France (P.G.S.)
- Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, France (P.G.S.)
- INSERM U-1148, Paris, France (P.G.S.)
- National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.)
| | - KyungAh Im
- Thrombolysis in Myocardial Infarction (TIMI) Study Group (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- Cardiovascular Division, Heart and Vascular Center (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Estella Kanevsky
- Thrombolysis in Myocardial Infarction (TIMI) Study Group (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- Cardiovascular Division, Heart and Vascular Center (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Yared Gurmu
- Thrombolysis in Myocardial Infarction (TIMI) Study Group (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- Cardiovascular Division, Heart and Vascular Center (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Itamar Raz
- Diabetes Unit, Division of Internal Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Israel (A.C., O.M., I.R.)
| | - Eugene Braunwald
- Thrombolysis in Myocardial Infarction (TIMI) Study Group (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- Cardiovascular Division, Heart and Vascular Center (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Benjamin M. Scirica
- Thrombolysis in Myocardial Infarction (TIMI) Study Group (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- Cardiovascular Division, Heart and Vascular Center (B.A.B., D.L.B., K.I., E.K., Y.G., E.B., B.M.S.), Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
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Han Y, Xie H, Liu Y, Gao P, Yang X, Shen Z. Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis. Cardiovasc Diabetol 2019; 18:96. [PMID: 31362743 PMCID: PMC6668189 DOI: 10.1186/s12933-019-0900-7] [Citation(s) in RCA: 212] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 07/22/2019] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Metformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD). METHODS Relevant studies reported before October 2018 was retrieved from databases including PubMed, EMBASE, Cochrane Library and Web of Science. Hazard ratio (HR) was calculated to evaluate the all-cause mortality, cardiovascular mortality and incidence of cardiovascular events (CV events), to figure out the level of left ventricular ejection fraction (LVEF), creatine kinase MB (CK-MB), type B natriuretic peptide (BNP) and to compare the average level of low density lipoprotein (LDL). RESULTS In this meta-analysis were included 40 studies comprising 1,066,408 patients. The cardiovascular mortality, all-cause mortality and incidence of CV events were lowered to adjusted HR (aHR) = 0.81, aHR = 0.67 and aHR = 0. 83 respectively after the patients with CAD were given metformin. Subgroup analysis showed that metformin reduced all-cause mortality in myocardial infarction (MI) (aHR = 0.79) and heart failure (HF) patients (aHR = 0.84), the incidence of CV events in HF (aHR = 0.83) and type II diabetes mellitus (T2DM) patients (aHR = 0.83), but had no significant effect on MI (aHR = 0.87) and non-T2DM patients (aHR = 0.92). Metformin is superior to sulphonylurea (aHR = 0.81) in effects on lowering the incidence of CV events and in effects on patients who don't use medication. The CK-MB level in the metformin group was lower than that in the control group standard mean difference (SMD) = - 0.11). There was no significant evidence that metformin altered LVEF (MD = 2.91), BNP (MD = - 0.02) and LDL (MD = - 0.08). CONCLUSION Metformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. Metformin has a better effect of reducing the incidence of CV events than sulfonylureas.
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Affiliation(s)
- Yechen Han
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
- Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100005, China
| | - Hongzhi Xie
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
- Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100005, China
| | - Yongtai Liu
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
- Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100005, China
| | - Peng Gao
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
- Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100005, China
| | - Xufei Yang
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
- Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100005, China
| | - Zhujun Shen
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
- Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100005, China.
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