This study evaluated healthcare resource utilization (HCRU) and costs in the USA for people with type 2 diabetes (T2D) who discontinued the injectable glucagon-like peptide 1 receptor agonist (GLP-1 RA) once-daily liraglutide for T2D (with no other glucose-lowering agent added) or switched from liraglutide to the GLP-1 RA once-weekly semaglutide for T2D.

In this observational cohort study, we utilized claims data (Merative MarketScan [Merative, Ann Arbor, MI, USA] Commercial and Medicare Database; January 1, 2017-March 31, 2021) to compare HCRU and costs between individuals who discontinued liraglutide ("discontinuers") and those who switched from liraglutide to semaglutide ("switchers"). Patients were indexed between January 1, 2018 and March 31, 2020. Outcomes were compared between discontinuers and switchers over the 360-day post-index period using stabilized inverse probability of treatment weighting.

Characteristics of the two cohorts were balanced after weighting. Switchers had significantly lower HCRU in inpatient and emergency department (ED) settings compared with discontinuers. Mean [standard deviation] total medical costs were significantly lower for switchers ($8513 [$18,931]) than for discontinuers ($13,585 [$52,011], p < 0.001), driven by reduced inpatient costs (2.6 times lower) and ED costs (1.6 times lower).

This analysis demonstrates that the cohort of people switching from liraglutide to semaglutide was associated with significantly lower HCRU and costs when compared with people discontinuing liraglutide only. These findings imply that switching to semaglutide could be a good option for people with T2D for whom liraglutide is no longer optimal.

Individuals with prediabetes have a higher risk of cardiovascular events and diabetes mellitus. Therefore, the prevention or delay of prediabetes progression to diabetes via lifestyle modification and medications is an important measure to reduce morbidity and mortality in this population. Based on the American Diabetes Association (ADA) guidelines, metformin is the only recommended drug for prediabetes. A growing body of evidence has shown the beneficial effects of sodium-glucose transporter 2 (SGLT-2) inhibitors in prediabetes. These drugs offer cardiovascular mortality benefits over metformin. This review aimed to summarize current evidence about the clinical effects of SGLT-2 inhibitors in prediabetes.

Patients with poor perioperative glycaemic control after total joint arthroplasty are at an increased risk of complications, mortality, delayed return to function and increased costs of care. Although correction of hyperglycaemia has been shown to improve patient outcomes, there is a lack of consensus regarding optimal perioperative glucose management after total joint replacement surgery. This pilot study aims to assess the feasibility of performing a multicentre randomised controlled trial to investigate the effect of perioperative metformin use on glycaemic control in the setting of total joint arthroplasty.

This blinded, placebo-controlled, pilot randomised controlled trial will enrol 40 participants aged 18-99 years undergoing total hip or knee arthroplasty at a single academic tertiary centre. Patients will be randomly allocated to two groups of 20 participants each and will receive metformin or a placebo, respectively, for 2 weeks preoperatively, continued on the day of surgery, and up to 2 days postoperatively. The primary outcome is a composite of four endpoints to assess study feasibility: timely recruitment, timely study drug administration, protocol adherence and retention. Secondary outcomes include perioperative glycaemic variability, sliding scale insulin utilisation, hospital length of stay and 90-day rates of infection, mortality and readmission. Analyses will be on an intention-to-treat basis.

The protocol was approved by Oregon Health & Science University Institutional Review Board, STUDY00025798. Written informed consent will be obtained for study participation. Findings will be disseminated via publication in peer-reviewed journals and conference presentations.

NCT06280274.

The aim of this study is to assess the impact of Ramadan intermittent fasting on glycemic control in individuals diagnosed with type 2 diabetes.

This historical prospective study utilized electronic health records from a major state-mandated healthcare provider. The research sample included Muslim adults aged 40-70 years, who had been diagnosed with type 2 diabetes. Their place of residence, categorized as a yes/no predominantly Muslim-Arab city, was identified for analysis purposes. Data regarding fasting plasma glucose and HbA1C levels were extracted from the 90 days preceding and the 45 days following the Ramadan period, spanning across six years (2011-2016). The annual data were aggregated and analyzed using a mixed-model ANOVA.

Muslim participants during Ramadan were found to have a higher likelihood of experiencing a change in HbA1C levels of ≥ 0.5 % compared to their non-Muslim counterparts, displaying an odds ratio (OR) of 1.89 (95 % confidence interval [CI]: 1.24-2.88). Among Muslims with initially normal HbA1C levels (≤7 %), there was a heightened risk of both decreased (≤-0.5 %) HbA1C levels (OR=2.62, 95 % CI: 1.15-6.00) and increased (≥+0.5 %) HbA1C levels (OR=2.85, 95 % CI: 1.24-6.57) in comparison to the non-Muslim group.

In Muslims with type 2 diabetes, fasting during the Ramadan increases the risk of their HbA1C-levels rising by more than 0.5 %. These results underscore the potentially dual impact of Ramadan intermittent fasting on glycemic control in individuals with type 2 diabetes.

Peripheral arterial disease (PAD) is characterized by atherosclerotic arterial occlusive disease of the lower extremities and is associated with an increased risk of major adverse cardiovascular events (MACE) in addition to disabling clinical sequelae, including intermittent claudication and chronic limb-threatening ischemia (CLTI). Given the growing burden of disease, knowledge of modern practices to prevent MACE and major adverse limb events (MALE) is essential. This review article examines evidence for medical management of PAD and its associated risk factors, as well as wound prevention and care.

A thorough review of the literature was performed, with attention to evidence for the management of modifiable atherosclerotic risk factors, claudication symptoms, wound prevention, and wound care.

Contemporary management of PAD requires a multi-faceted approach to care, with medical optimization of smoking, hypertension, hyperlipidemia, and diabetes mellitus. The use of supervised exercise therapy for intermittent claudication is highlighted. The anatomic disease patterns of smoking and diabetes mellitus are discussed further, and best practices for diabetic foot ulcer prevention, including offloading footwear, are described. Quality wound care is essential in this patient population and involves strategic use of debridement, wound-healing adjuncts, and skin substitutes, when appropriate.

The objective of medical management of PAD is to reduce the risk of MACE and MALE. Atherosclerotic risk factor optimization, appropriate wound care, and management of diabetic foot ulcers, foot infections, gangrene, and chronic, non-healing wounds are critical components of PAD care. Interdisciplinary care is essential to coordinate care, leverage expertise, and improve outcomes.

Case reports of postoperative diabetic ketoacidosis in patients using sodium-glucose cotransporter 2 inhibitor (SGLT2i) medications underlie guidance by the US Food and Drug Administration to withhold SGLT2i medication for at least 3 days prior to surgery. Given the potential negative consequences associated with preoperative medication withholding, a large-scale evaluation of the risk of diabetic ketoacidosis in this population is needed.

To estimate the association between preoperative SGLT2i medication use and postoperative diabetic ketoacidosis in a population of patients who underwent a variety of emergency surgeries. Emergency surgery was chosen given the assumption that a patient would be unable to withhold their SGLT2i medication per the current guidance.

This retrospective cohort study was conducted among a nationwide sample of patients aged 18 years or older with type 2 diabetes who were enrolled in commercial or Medicare fee-for-service insurance plans and who underwent 1 of 13 emergency surgeries between January 1, 2016, and December 15, 2022. Emergency surgeries were defined as those occurring on the same day or the 1 to 2 days after an emergency department claim. Data were analyzed from November 2023 through December 2024.

SGLT2i medication use.

Diabetic ketoacidosis, defined by diagnosis codes, in the 0 to 14 days after surgery.

Among 34 671 patients with type 2 diabetes who underwent emergency surgery (mean [SD] age, 63.9 [14.0] years; 19 175 female [55.3%] and 15 496 male [44.7%]), the most common surgeries were laparoscopic cholecystectomy (9385 patients) and transurethral procedures (12 246 patients). There were 2607 patients (7.5%) who used SGLT2i medications and 32 064 patients (92.5%) who did not. Unadjusted incidence of diabetic ketoacidosis was 127 patients (4.9%) for those exposed to SGLT2i medications and 1115 patients (3.5%) for those unexposed. After accounting for covariates, including demographic characteristics, indicators of diabetic severity, comorbidities, and surgery type, the incidence of the outcome was 3.8% for those exposed to SGLT2i medications and 3.5% for those unexposed. The average treatment effect [ATE] was 0.2% (95% CI, -1.7% to 2.2%). Results were robust to alternate specifications (eg, intensive care unit-level care as the outcome: ATE, -1.0%; 95% CI, -2.9% to 1.1%).

This study found that preoperative use of SGLT2i medications in patients undergoing emergency surgery was not associated with an increased risk for postoperative diabetic ketoacidosis compared with no use of SGLT2i medications. These findings may justify liberalizing current guidance on preoperative SGLT2i medication withholding periods.

Diabetes mellitus (DM) and neuroendocrine tumors (NET) can exert unfavorable effects on each other prognosis. In this narrative review, we evaluated the effects of NET therapies on glycemic control and DM management and the effects of anti-diabetic therapies on NET outcome and management. For this purpose, we searched the PubMed, Science Direct, and Google Scholar databases for studies reporting the effects of NET therapy on DM as well as the effect of DM therapy on NET. The majority of NET treatments appear to impair glycaemic control, both inducing hypoglycemic or, more commonly, hyperglycemia and even new-onset DM. However, glucose metabolism imbalance can be effectively managed by modulating anti-diabetic therapy and adopting an appropriate nutritional approach. On the other hand, the effects of anti-diabetic treatment, like insulin, sulfonylureas, thiazolidinediones, ipeptidyl-peptidase-4 inhibitors, Glucagon-like peptide-1 receptor agonists, and Sodium-glucose cotransporter-2 inhibitors on NET are unclear. Recently, metformin has been investigated in patients with gastroenteropancreatic NET resulting in improved progression free survival suggesting a potential antineoplastic role. Finally, the management of DM in patients with NET is of great clinical relevance to correctly perform radiological procedures and even more functional imaging procedures, as well as to optimize the therapy and avoid treatment withdrawal or discontinuation. In conclusion, understanding the mechanisms underlying therapy-induced DM and implementing appropriate monitoring and management strategies of DM are essential for optimizing NET patient outcome and quality of life.

The aim of this study was to elucidate the potential mechanism of the antihyperglycemic action of the donut-shaped Preyssler-Pope-Jeannin polyanion salt (NH4)14[NaP5W30O110] 31H2O (NaP5W30) and its effect on metabolic disorders associated with diabetes. For this purpose, relevant parameters of blood glucose regulation, lipid profile, and electrolyte status were monitored in streptozotocin (STZ)-induced diabetic rats that were orally treated with 20 mg/kg/day NaP5W30 for three weeks. The serum insulin concentration was increased in diabetic animals treated with NaP5W30 (20 mg/kg/day, per os, three weeks), which could be one of the possible mechanisms of the confirmed antihyperglycemic effect. In addition, the administration of NaP5W30 significantly reduced hyperglycemia and glycated haemoglobin A1c (HbA1c) in STZ-induced diabetic rats, although normoglycemic values were not achieved. Furthermore, a statistically significant 1.3-fold reduction in serum total cholesterol and a 1.7-fold reduction in high-density lipoprotein (HDL) cholesterol were observed in the NaP5W30 treatment group compared to the diabetic control group. In contrast, NaP5W30 had no effect on homeostasis model assessment of insulin resistance (HOMA-IR) index values, electrolyte concentrations, or serum concentrations of low-density lipoprotein (LDL) cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), or total triglycerides. In summary, NaP5W30 effectively improved glycoregulation in diabetic rats via the considerable stimulation of insulin as a putative mechanism. Moreover, NaP5W30 did not affect rat weight or disrupt lipid and electrolyte status, common diabetes-followed side effects and risk factors for various life-threatening complications. Thus, NaP5W30 could be considered a promising antidiabetic drug-candidate that deserves further investigation.

Insulin aspart, a rapid-acting analog, achieves faster subcutaneous absorption than regular insulin. This study aimed to demonstrate equivalence in the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of Recombinant Human Insulin Aspart from BioGenomics Limited (as test) and Novo-Nordisk (as reference) in healthy adult males. This was a double-blind, randomized, cross-over study, assessing PK and PD parameters under fasting conditions. Participants received either 0.2 U/kg of test or reference product via a subcutaneous route in the abdominal area. PK parameters included maximum serum concentration (Cmax), area under the curve [(AUC[0-t]) and (AUC [0-∞])], time to maximum serum concentration (Tmax), and half-life (t½). PD parameters included amount of glucose infused (Gtot), maximum glucose infusion rate (Rmax), time of Rmax (tRmax), late time of half-maximal glucose infusion rate (tRmax50), time of first measured glucose infusion rate (tonset), and cessation of glucose infusion/clamp (tRlast). Seventy subjects between 18 and 45 years of age and body mass index between 18 and 27 kg/m2 were enrolled. The 90% confidence intervals (CIs) for Cmax, AUC[0-t], AUC [0-∞] for insulin, and the 95% CIs for Gtot, Rmax for glucose were within 80%-125% as required to assess test-reference bioequivalence. No serious adverse events were observed. Both the preparations showed bioequivalence under fasting conditions with a similar safety profile.

Hypoglycemic pharmacotherapy interventions for alleviating the risk of dementia remain controversial, particularly regarding dipeptidyl peptidase 4 (DPP4) inhibitors vs metformin. Our objective was to investigate whether the initiation of DPP4 inhibitors, as opposed to metformin, was linked to a reduced risk of dementia.

We included individuals with type 2 diabetes over 40 years old who were new users of DPP4 inhibitors or metformin in the Chinese Renal Disease Data System database between 2009 and 2020. The study employed Kaplan-Meier and Cox regression for survival analysis and the Fine and Gray model for the competing risk of death.

Following a 1:1 propensity score matching, the analysis included 3626 DPP4 inhibitor new users and an equal number of metformin new users. After adjusting for potential confounders, the utilization of DPP4 inhibitors was associated with a decreased risk of all-cause dementia compared to metformin [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.45-0.89]. Subgroup analysis revealed that the utilization of DPP4 inhibitors was associated with a reduced incidence of dementia in individuals who initiated drug therapy at the age of 60 years or older (HR 0.69, 95% CI 0.48-0.98), those without baseline macrovascular complications (HR 0.62, 95% CI 0.41-0.96), and those without baseline microvascular complications (HR 0.67, 95% CI 0.47-0.98).

In this real-world study, we found that DPP4 inhibitors presented an association with a lower risk of dementia in individuals with type 2 diabetes than metformin, particularly in older people and those without diabetes-related comorbidities.

People with type 2 diabetes mellitus who have clinical inertia often struggle to control their blood sugar levels and do not receive timely treatment intensification. Strict glycemic control has advantages, but many patients with diabetes are unable to reach their target blood sugar levels. The study's main objective was to determine the prevalence of clinical inertia in patients with type 2 diabetes at Debre Tabor Comprehensive Specialized Hospital(DTCSH) in Ethiopia.

An institutional based, cross-sectional research design was used at Debre Tabor Comprehensive Specialized Hospital from November 20/2023 to January 30/2024. A structured questionnaire modified from various medical records and literatures were used to gather data. A logistic regression model was also employed after the Hosmer-Lemeshow goodness-of-fit test was checked to find contributing variables to clinical inertia. A threshold of p < 0.05 was considered statistically significant.

In total, 287 samples were included in the research. The occurrences of clinical inertia 31.4% (95%CI: 25.9 - 36.8) were obtained from 90 patients. Aged patients (AOR = 1.103; 95% CI, 1.034 - 1.176; P = 0.003), medication fee (AOR = 4.955; 95% CI, 1.284 - 14.127; P = 0.020), medication nonadherence (AOR = 4.345; 95% CI, 2.457 - 15.537; P = 0.001), increase number of medication (AOR = 4.205; 95% CI, 2.657- 6.655; P ≤ 0.001), poor glycemic control (AOR = 2.253; 95% CI, 1.673 - 3.033; P ≤ 0.001) were more likely to have clinical inertia.

One-third of patients experienced clinical inertia. Age, glycemic control, medication non-adherence, treatment fee, and number of medications were found to be strongly correlated with clinical inertia. More precise knowledge of the clinical inertia and the associated therapies is necessary to tackle this issue more effectively.

For people with diabetes on insulin injection therapy, insulin pen dose accuracy and reliability are key features. Dose accuracy of the Tempo PenTM with attached Tempo Smart ButtonTM [Module] (the system) was tested for three doses under standard atmospheric conditions. Reliability and the ability of the Module to detect, store, and transmit dose-related data were also tested. The system met the International Organization for Standardization 11608-1:2014 requirements for dose accuracy at all doses. Mean (standard deviation) doses were 0.010 mL (0.002), 0.299 mL (0.002), and 0.597 mL (0.004) for the 0.010-mL, 0.300-mL, and 0.600-mL doses, respectively. The Module also met requirements for data transfer after every injection. The system accurately delivered doses and reliably captured and stored insulin dosing information.

New onset diabetes mellitus after organ transplantation (NODAT) is a frequent and serious complication of solid organ transplantation. It significantly impacts graft function, patient survival, and quality of life. NODAT is diagnosed based on the criteria for type 2 diabetes, with the oral glucose tolerance test (OGTT) serving as the gold standard for diagnosis. The development of NODAT is influenced by a range of risk factors, which are classified into modifiable and non-modifiable categories. Post-transplant, regular glycemic monitoring at specific intervals is essential for timely diagnosis and initiation of therapy. Early intervention can help prevent or delay the onset of diabetes-related complications. The treatment strategy for NODAT involves lifestyle modifications and pharmacological interventions. These include medications such as metformin, sulfonylureas, glinides, thiazolidinediones, DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and insulin. Adjusting immunosuppressive therapy-either by reducing dosages or substituting drugs with lower diabetogenic potential-is a common preventative and therapeutic measure. However, this must be performed cautiously to avoid acute graft rejection, which poses a greater risk to the patient compared to NODAT itself. In addition to managing diabetes, addressing comorbidities such as hypertension and dyslipidemia is crucial, as they elevate the risk of cardiovascular events and mortality. Patients with NODAT are also prone to developing common diabetes-related complications, including diabetic nephropathy, neuropathy, retinopathy, and peripheral vascular disease. Therefore, regular follow-ups and appropriate treatment are vital to maintaining quality of life and improving long-term outcomes.

The relationship between diabetes mellitus (DM) and asthma is complex and can impact disease trajectories.

To explore the bidirectional influences between the two conditions on clinical outcomes and disease control.

We systematically reviewed the literature on the relationship between DM and asthma, focusing on their impacts, mechanisms, and therapeutic implications. Various studies were assessed, which investigated the effect of glycemic control on asthma outcomes, lung function, and exacerbations. The study highlighted the role of specific diabetes medications in managing asthma.

The results showed that poor glycemic control in diabetes can exacerbate asthma, increase hospitalizations, and reduce lung function. Conversely, severe asthma, especially in obese individuals, can complicate diabetes management and make glycemic control more difficult. The diabetes-associated mechanisms, such as inflammation, microangiopathy, and oxidative stress, can exacerbate asthma and decrease lung function. Some diabetes medications exhibit anti-inflammatory effects that show promise in mitigating asthma exacerbations.

The complex interrelationship between diabetes and asthma suggests bidirectional influences that affect disease course and outcomes. Inflammation and microvascular complications associated with diabetes may worsen asthma outcomes, while asthma severity, especially in obese individuals, complicates diabetes control. However, the current research has limitations, and more diverse longitudinal studies are required to establish causal relationships and identify effective treatment strategies for individuals with both conditions.

This narrative review examines the dynamic interplay between carbohydrate intake and diabetes medications, highlighting their combined molecular and clinical effects on glycemic control. Carbohydrates, a primary energy source, significantly influence postprandial glucose regulation and necessitate careful coordination with pharmacological therapies, including insulin, metformin, glucagon-like peptide (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Low-glycemic-index (GI) foods enhance insulin sensitivity, stabilize glycemic variability, and optimize medication efficacy, while high-GI foods exacerbate glycemic excursions and insulin resistance. Continuous glucose monitoring (CGM) offers real-time insights to tailor dietary and pharmacological interventions, improving glycemic outcomes and reducing complications. Despite advancements, gaps persist in understanding nutrient-drug interactions, particularly with emerging antidiabetic agents. This review underscores the need for integrating carbohydrate-focused dietary strategies with pharmacotherapy to enhance diabetes management. Future research should prioritize clinical trials leveraging CGM technology to explore how glycemic index, glycemic load, and carbohydrate quality interact with newer diabetes medications. Such studies can refine evidence-based recommendations, support individualized care plans, and improve long-term outcomes. Addressing systemic barriers, such as limited access to dietitians and CGM technology in underserved regions, is critical for equitable care. Expanding the roles of community health workers and training healthcare providers in basic nutrition counseling can bridge gaps, promoting sustainable and inclusive diabetes management strategies. These efforts are essential for advancing personalized, effective, and equitable care for individuals with diabetes.

Type 2 diabetes (T2D) and its complications disproportionally affect American Indian and Alaska Native (AI/AN) peoples. Prescribing decisions for anti-diabetic medications are complicated and require balancing medication benefits, costs and side effects. Little is known about trends in anti-diabetic medication use as well as acute diabetes complications among AI/AN adults. Here, we examined patterns and trends in anti-diabetic medication use and rates of hospital admissions or emergency department (ED) visits due to severe hypoglycaemia and hyperglycaemia among AI/AN adults with T2D.

We conducted a retrospective analysis of Indian Health Service (IHS) Improving Health Care Delivery Data Project. A total of 39 183 AI/AN adults aged ≥18 years with T2D who used IHS or Tribal health services during any of the fiscal years (FYs) 2009-2013 were included. Utilization rates of each class of anti-diabetic medications and rates of severe hypoglycaemia and severe hyperglycaemia in emergency room and/or inpatient discharge diagnoses were calculated for each year. Longitudinal statistical models were fitted to examine time trends of anti-diabetic medication use and complications.

During 2009-2013, use of metformin (56.0%-60.5%), insulin (31.4%-35.9%) and dipeptidyl peptidase-4 inhibitors (1.4%-9.0%) increased, whereas the use of sulfonylureas (40.3%-32.9%) and thiazolidinediones (TZDs, 31.6%-8.8%) decreased significantly. Trends in severe hypoglycaemia (1.6%-0.8%) and severe hyperglycaemia (2.0%-1.6%) declined gradually.

There were significant changes in the utilization of different anti-diabetic medication classes during 2009-2013 among AI/AN adults with T2D. Concurrently, there were significant reductions in severe hypoglycaemia and severe hyperglycaemia.

Empagliflozin might lower the risk of diabetic retinopathy (DR) by preventing retinal pericyte loss. However, the role of empagliflozin with respect to DR in patients with type 2 diabetes (T2D) remains unclear.

To compare the risk of incident nonproliferative DR (NPDR) and DR progression in patients with T2D initiating empagliflozin vs a dipeptidyl peptidase 4 inhibitor (DPP4i).

A new-user active-comparator cohort study was conducted using US nationwide insurance claims data from 2 commercial insurers and Medicare from August 2014 to September 2019. Adults with T2D initiating study drugs without prior diagnosis or treatment for proliferative DR or other advanced retinal diseases were included. To assess incident NPDR, patients with a history of NPDR were additionally excluded, while for the DR progression outcome, patients were required to have a history of NPDR. Data were analyzed from August 2022 to May 2024.

Initiation of empagliflozin or a DPP4i.

Incident NPDR was defined using diagnostic codes for mild, moderate, or severe NPDR. The DR progression outcome was defined as a composite of incident proliferative DR, vitreous hemorrhage, initiation of intravitreal anti-vascular endothelial growth factor injection, or panretinal photocoagulation. Incidence rates, hazard ratios (HRs), and rate differences (RDs) with 95% CIs were estimated.

A total of 34 239 pairs of propensity-score matched adults were identified in the incident NPDR cohort and 7831 pairs in the DR progression cohort. In the incident NPDR cohort, 35 867 patients (52.4%) were male, and the mean (SD) age was 65.6 (10.3) years. In the DR progression cohort, 8229 patients (52.5%) were male, and the mean (SD) age was 67.0 (10.0) years. Over a mean (SD) follow-up period of 8 (7.5) months receiving treatment, the risk of incident NPDR was not different across groups (HR, 1.04; 95% CI, 0.94 to 1.15; RD, 1.30; 95% CI, -1.83 to 4.44), while the risk of DR progression was lower among individuals who initiated empagliflozin compared with those who began DPP4i therapy (HR, 0.78; 95% CI, 0.63 to 0.96; RD, -9.44; 95% CI, -16.90 to -1.98). Results were consistent across multiple subgroups and sensitivity analyses.

Compared with initiation of a DPP4i, empagliflozin initiation was not associated with incident NPDR, although it may be associated with a lower risk of DR progression. Although residual confounding cannot be entirely ruled out due to the observational nature of our study, these findings may be helpful when weighing the risks and benefits of various glucose-lowering agents in adults with T2D.

To investigate the characteristics of psychological insulin resistance and dyadic coping in elderly diabetic patients and their spouses, and their association with insulin medication adherence.

Observational, cross-sectional study.

A convenience sampling method selected 300 elderly diabetic patient-spouse pairs from a community. Data were collected using general information questionnaires, the My Views on Insulin questionnaire, Dyadic Coping questionnaire, and ARMS refill and medication adherence questionnaire. Latent Profile Analysis (LPA) was used to categorize the "psychological-coping" patterns of psychological insulin resistance and dyadic coping among these pairs. Multiple linear regression analysis identified factors influencing insulin medication adherence.

Four latent classes were identified: patients and spouses with low resistance-high coping (30.3%), patients with low resistance-moderate coping and spouses with high resistance-low coping (16.3%), patients with high resistance-moderate coping and spouses with moderate resistance-high coping (33.7%), patients and spouses with high resistance-low coping (19.7%). Multiple linear regression analysis showed that the number of chronic diseases a patient has, the use of oral hypoglycemic agents, family per capita monthly income, and latent classes of psychological insulin resistance and dyadic coping significantly affected insulin medication adherence (P<0.05).

It is crucial to consider the psychological insulin resistance and dyadic coping of both patients and their spouses, include both in health plans, and develop comprehensive intervention strategies that address the couple as a unit.

This study informs healthcare professionals by raising awareness of the different "psychological-coping" characteristics between elderly diabetic patients and their spouses, with insulin medication adherence and reducing the likelihood of readmission.

To compare the efficacy of exercise, metformin and their combination on glucose metabolism in individuals with abnormal glycaemic control.

Systematic review and network meta-analysis.

Embase, Web of Science, PubMed/MEDLINE and SPORTDiscus.

Randomised controlled trials involving exercise, metformin or their combined treatments in individuals with prediabetes or type 2 diabetes mellitus (T2DM) were included. Outcomes included haemoglobin A1c (HbA1c), 2-hour glucose during oral glucose tolerance test, fasting glucose, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR).

407 articles with 410 randomised controlled trials (n=33 802) were included. In prediabetes, the exercise showed greater efficacy than metformin on HbA1c levels (mean difference -0.16%, 95% CI (-0.23 to -0.09) vs -0.10%, 95% CI (-0.21 to 0.02)), 2-hour glucose (-0.68 mmol/L, 95% CI (-0.97 to -0.39) vs 0.01 mmol/L, 95% CI (-0.38 to 0.41)) and HOMA-IR (-0.54, 95% CI (-0.71 to -0.36) vs -0.23, 95% CI (-0.55 to 0.10)), while the efficacy on fasting glucose was comparable (-0.26 mmol/L, 95% CI (-0.32 to -0.19) vs -0.33 mmol/L, 95% CI (-0.45 to -0.21)). In T2DM, metformin was more efficacious than exercise on HbA1c (-0.88%, 95% CI (-1.07 to -0.69) vs -0.48%, 95% CI (-0.58 to -0.38)), 2-hour glucose (-2.55 mmol/L, 95% CI (-3.24 to -1.86) vs -0.97 mmol/L, 95% CI (-1.52 to -0.42)) and fasting glucose (-1.52 mmol/L, 95% CI (-1.73 to -1.31) vs -0.85 mmol/L, 95% CI (-0.96 to -0.74)); exercise+metformin also showed greater efficacy in improving HbA1c (-1.23%, 95% CI (-2.41 to -0.05)) and fasting glucose (-2.02 mmol/L, 95% CI (-3.31 to -0.74)) than each treatment alone. However, the efficacies were modified by exercise modality and metformin dosage.

Exercise, metformin and their combination are efficacious in improving glucose metabolism in both prediabetes and T2DM. The efficacy of exercise appears to be superior to metformin in prediabetes, but metformin appears to be superior to exercise in patients with T2DM.

CRD42023400622.

Obesity and type 2 diabetes mellitus (T2DM) are chronic diseases with increasing prevalence, underscoring the urgent need for effective treatment and management strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an essential class of drugs for managing both obesity and T2DM, offering additional benefits for cardiovascular and kidney health. GLP-1 RAs work by targeting GLP-1 receptors, mimicking the effects of the natural hormone GLP-1 to regulate blood glucose levels, promote weight loss, and provide potential benefits for cardiovascular health. This narrative review evaluates the mechanisms of action, clinical efficacy, and broader roles of GLP-1 RAs in promoting weight loss and glycemic control. In addition, the present investigation explores recent clinical studies demonstrating the effectiveness of GLP-1 RAs in diabetic and nondiabetic populations, highlighting their potential in addressing obesity even in those without T2DM and describing probable benefits to cardiovascular health. Finally, our investigation outlines the importance of future research to further define the potential benefits of GLP-1 RAs.

Metformin is an essential medicine that is most widely prescribed frontline for the treatment of Type 2 diabetes (T2D). Metformin upgraded glycemic control in T2D patients without hypoglycemic effects in patients. This assessment aims to understand molecular mechanism mechanisms in non-responder patients to metformin.

Gene expression profiles of responder and non-responder T2D patients to metformin are extracted from Gene Expression Omnibus (GEO) and are evaluated by the GEO2R program to find the significant differentially expressed genes (DEGs). The significant DEGs have been studied via action map gene ontology analyses.

Results indicate that 563 significant DEGs discriminate non-responders from responder groups. "NF-kappa B signaling pathway" and 11 DEGs including BIRC3, CCL4L2, CXCL2, ICAM1, LYN, MYD88, RELA, SYK, TLR4, TNFAIP3, and TRIM25 were pointed out as core of drug resistance.

It can be concluded that there are differences between gene expression analysis, the response of diabetic patients to metformin. Results indicate that dysregulation of the "NF-kappa B signaling pathway" and TNFAIP3, BIRC3, RELA, MYD88, TLR4, and ICAM1 is associated with drug resistance in T2D patients.

Type II Diabetes mellitus (T2DM) patients often do not achieve glycemic control with oral hypoglycemic agents (OHAs). There are two main approaches to address this challenge: transitioning to a triple OHA regimen, or adding Insulin to the existing dual OHA regimen.

This study aimed to compare the efficacy of adding Insulin to dual OHAs (Sitagliptin + Metformin) against adding a third OHA to Sitagliptin + Metformin in achieving glycemic control among patients with uncontrolled T2DM.

A pre-post study was conducted between 21 September 2023 and 21 December 2023 at Services Hospital Peshawar, Pakistan. Patients with uncontrolled T2DM with >7% HbA1c were divided into group 1 (Sitagliptin + Metformin plus a third OHA), and group 2 (Sitagliptin + Metformin plus pre-mixed Insulin 70/30). Glycemic control based on HbA1c values, fasting and random blood sugar levels, lipid profile, and body weight were evaluated after 3 months of therapy. The pre- and post- effect was compared by using a paired t-test.

The study included n = 80 patients with T2DM. Between groups 1 and 2, no significant difference was found in HbA1c values (9.1 vs. 9, with p = 0.724). However, BMI, cholesterol, and LDL significantly decreased in group 1 compared to group 2 (p<0.001 vs. p = 0.131, p = 0.023 vs. p = 0.896, and p = 0.003 vs. p = 0.395, respectively). Additionally, the incidence of hypoglycemic episodes was significantly lower in group 1 (7.5%) than in group 2 (47.5%, p = 0.004). No significant difference was observed between the triple OHA and dual OHA plus Insulin regimens in achieving glycemic control.

The triple OHA regimen improved BMI, cholesterol, and LDL levels, and reduced hypoglycemic episodes more effectively than dual OHA plus Insulin, despite similar HbA1c outcomes, suggesting it may be preferable for uncontrolled T2DM.

Adherence and treatment continuation rates of the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide for both oral (O-SEMA) and subcutaneous injection (SEMA-SC) remain unknown in real-world clinical practice. This retrospective observational study compared the 12 month adherence and treatment discontinuation of O-SEMA and once-weekly SEMA-SC in patients with type 2 diabetes using a real-world claims database. SEMA-SC initiators were 1:1 propensity score-matched to O-SEMA initiators. Non-adherence was defined as <0.8 of the proportion of days covered. SEMA-SC had a significantly higher odds ratio (OR) for non-adherence than O-SEMA (OR: 1.39). The hazard ratio for treatment discontinuation, using O-SEMA as the reference, was 1.45 for SEMA-SC, although the discontinuation rate of O-SEMA was higher during the early stage. O-SEMA initiators showed significantly higher adherence and greater persistence in therapy than SEMA-SC initiators at 12 months, which could lead to earlier initiation of GLP-1RA treatment.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Key pharmacotherapeutic modalities and considerations for the patient with ST-elevation myocardial infarction (STEMI) across the later phases of inpatient care are reviewed.

Published descriptions and validation of clinical pharmacist roles specific to the acute management of STEMI are limited. This high-risk period from presentation through revascularization, stabilization, and hospital discharge involves complex pharmacotherapeutic decision points, many operational medication needs, and multiple layers of quality oversight. A companion article reviewed STEMI pharmacotherapy from emergency department presentation through revascularization. Herein we complete the pharmacotherapy review for the STEMI patient across the inpatient phases of care, including the management of peri-infarction complications with vasoactive and antiarrhythmic agents, considerations for postrevascularization antithrombotics, and assessments of supportive therapies and secondary prevention. Key guideline recommendations and literature developments are summarized from the clinical pharmacist's perspective alongside suggested pharmacist roles and responsibilities. Considerations for successful hospital discharge after STEMI and pharmacist involvement in associated institutional quality improvement efforts are also provided. We aim to support inpatient pharmacy departments in advancing clinical services for this critical patient population and call for further research delineating pharmacists' impact on patient and institutional STEMI outcomes.

This study aimed to evaluate the bioequivalence between test and reference insulin degludec (IDeg) and the effects of body composition on pharmacokinetics and pharmacodynamics of IDeg in Chinese healthy volunteers. In this randomized, open-label, crossover trial, 30 healthy Chinese males were assigned to receive a single subcutaneous dose (0.4 IU/kg) of each formulation under 24-h euglycemic hyperinsulinaemic clamp. Body compositions were analysed prior to administration and blood samples were collected at specific times. The 90% of primary pharmacokinetic parameters and 95% of primary pharmacodynamic parameters confidence intervals for the ratio of the least-squares geometric means were all in the range of 80-125%. As the fat content level increases, Cmax, AUC0-12 and GIR-AUC0-24 decreased whereas AUC24-96 increased sequentially. Therefore, the equivalence was demonstrated between test and reference, and in healthy Chinese volunteers, higher levels of adiposity are associated with slower rates of insulin absorption and distribution and the poorer glucose-lowering effect.

To review and validate a questionnaire on knowledge of injectable insulin management (JH-SEFAC) by patients with diabetes for use in community pharmacies.

Study design: cross-sectional observational in Spanish community pharmacies during the first half of 2023. Inclusion criteria: patients with diabetes, of legal age, on insulin treatment. Questionnaire design: a nominal group of community pharmacists reviewed and piloted the initial questionnaire to determine its feasibility. It was approved by the CEIC of Aragón (PI22/375). Content validation: by a multidisciplinary group of experts in diabetes, using an ad hoc evaluation questionnaire of 10 questions (Likert scale of 1-5). Reliability: by means of the internal consistency index (Cronbach's alpha) and the intraclass correlation coefficient (ICC). Reproducibility (test/retest): the results of the questionnaire administered twice 2-3 weeks apart to the group of patients were compared. Pharmacists members of the SEFAC Diabetes Working Group collaborated. Sample: calculated in 127 subjects (95% CI and precision of 10%).

20 community pharmacies from 13 autonomous communities included 131 patients. The expert assessment was 4.52 out of 5 (90.4%). The Keiser-Meyer-Olkin test was 0.626 and Bartlett's test was significant (p<0.001). The Cronbach's alpha of the global questionnaire was 0.804 and the ICC was 0.902. The mean score of the questionnaire was 15.98 out of 31 points.

The JH-SEFAC questionnaire was validated to evaluate the management of insulin injectables, providing community pharmacists with a valuable tool for therapeutic education.

Methotrexate (MTX) is widely prescribed to treat different malignancies as well as autoimmune diseases. However, it causes a range of side effects in different organs such as testis. This study aims to clarify the role of dipeptidyl peptidase 4 (DPP4) in MTX-induced testicular damage via pathways involved in oxidative stress and evaluates the protective effects of sitagliptin as a DPP4 inhibitor. Twenty-four animals randomly allocated into four groups including: (I) control, (II) MTX (20 mg/kg, i.p.), (III) sitagliptin (20 mg/kg, i.p., for four consecutive days), and MTX + sitagliptin in which received chemicals resembling group II and III. Histopathological examinations conducted to assess the structural changes in testes of different experimental groups. Also, ELISA method employed to investigate the levels of DPP4, AKT, p-AKT, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). In addition, the total malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) were assessed. The results indicated that MTX administration was accompanied with testicular damage, which reversed by sitagliptin treatment. The biochemical observations demonstrated that MTX markedly increased the levels of DPP4, decreased p-AKT/AKT ratio followed by a marked decrement in Nrf2 and HO-1 levels. Also, it was observed that MTX decreased the activity of SOD and increased total MDA content in testicular specimen. However, sitagliptin treatment diminished mentioned alterations effectively. Altogether, our findings supported the possible role of DPP4 in MTX-induced testicular toxicity along with the potential protective features of sitagliptin via suppressing of the histopathological and biochemical alterations induced by MTX.

Cardiovascular disease (CVD) can be recurrent during type 2 diabetes (T2D) progression in this aging population. The effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy on total (ie, first and subsequent) CVD among patients with T2D in clinical practice remains uncertain.

To analyze the comparative association of SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP4i) therapy with total CVD among patients with T2D in clinical practice.

This retrospective cohort study used electronic medical records at the National Cheng Kung University Hospital, a leading medical center in Taiwan, from 2015 through 2021. Adult patients with T2D who initiated first use of the study drugs from 2016 through 2019, with up to 6 years of follow-up, were identified.

The primary outcomes included total composite CVD events and individual CVD subtypes (ie, atrial fibrillation, coronary heart disease, heart failure, stroke, myocardial infarction, and transient ischemic attack). A shared frailty model analysis was used to assess the association of treatment with repeat CVD events. Data from patients at high risk for CVD recurrence were further analyzed. Data were analyzed from September 1, 2022, to December 31, 2023.

Overall, 8384 patients with T2D were identified (mean [SD] age, 63.7 [12.4] years; 4645 [55.4%] male). A total of 1632 propensity score-matched pairs of SGLT2i (mean [SD] age, 57.8 [12.0] years; 673 [41.2%] female and 959 [58.8%] male) and DPP4i (mean [SD] age, 58.2 [12.9] years; 655 [40.1%] female and 977 [59.9%] male) users were included. SGLT2i was associated with reduced total CVD risk vs DPP4i therapy (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98]) but not the first CVD event (with the use of SGLT2i therapy were more prominent for patients at high risk of CVD (ie, HR, 0.70 [95% CI, 0.62-0.80] for individuals with estimated glomerular filtration rate lower than 60 mL/min/1.73 m2; HR, 0.70 [95% CI, 0.64-0.78]; for individuals having any diabetes-related complications; and HR, 0.72 [95% CI, 0.65-0.80] for individuals with a history of CVD) compared with the overall cohort. Among patients at high risk of CVD, greater reduced total CVD burden associated with SGLT2i therapy was observed for women vs men (eg, HR, 0.59 [95% CI, 0.49-0.72] in the subgroup with CVD history).

In this cohort study of patients with T2D, the use of SGLT2is vs DPP4is was associated with reduced total cardiovascular burden, suggesting that long-term use of this therapy may optimize treatment benefit among patients with chronic CVD. The SGLT2i-associated benefit among patients with high risk of CVD encourages the prioritization of SGLT2i use for these vulnerable individuals.

Metformin is one of the most commonly used oral hypoglycemic drugs in clinical practice, with unique roles in neurodegeneration and vascular lesions. Neurodegeneration and vasculopathy coexist in many diseases and typically affect the neurovascular unit (NVU), a minimal structural and functional unit in the central nervous system. Its components interact with one another and are indispensable for maintaining tissue homeostasis. This review focuses on retinal (diabetic retinopathy, retinitis pigmentosa) and cerebral (ischemic stroke, Alzheimer's disease) diseases to explore the effects of metformin on the NVU. Metformin has a preliminarily confirmed therapeutic effect on the retinal NUV, affecting many of its components, such as photoreceptors (cones and rods), microglia, ganglion, Müller, and vascular endothelial cells. Since it rapidly penetrates the blood-brain barrier (BBB) and accumulates in the brain, metformin also has an extensively studied neuronal protective effect in neuronal diseases. Its mechanism affects various NVU components, including pericytes, astrocytes, microglia, and vascular endothelial cells, mainly serving to protect the BBB. Regulating the inflammatory response in NVU (especially neurons and microglia) may be the main mechanism of metformin in improving central nervous system related diseases. Metformin may be a potential drug for treating diseases associated with NVU deterioration, however, more trials are needed to validate its timing, duration, dose, clinical effects, and side effects.

Background: Adolescence is a particularly crucial period of physical, emotional, and social development and adaptation, rendering these formative years rather challenging for individuals with chronic conditions like type 1 diabetes (T1D). Despite rapid improvement in diabetes therapies, adolescents with T1D are characterized by poorer adherence to treatment regimens compared with other pediatric age groups. Insufficient adherence is strongly related to low diabetes control, increasing morbidity, and risk for premature mortality. This study aimed to provide a comprehensive overview of adolescents' most common barriers to T1D adherence, stressing the need for a deep and comprehensive understanding of these barriers. The complexity of these barriers is underscored by the diverse factors contributing to poor T1D adherence in adolescents. Methods: A narrative review was conducted, surveying four databases (PubMed, Scopus, EMBASE, and Web of Science) for full-text articles in the English language published up to June 2024. All studies related to barriers to T1D adherence in adolescents were considered. The literature was selected using selection and exclusion criteria and extracted and organized using Mendeley. Exclusion criteria included studies with insufficient data and non-peer-reviewed articles. This review revealed that adolescents face numerous obstacles to T1D adherence related to psychological factors, flux in family dynamics, perceived social pressures, therapy-related factors, transitioning responsibility, risk-taking behaviors, and pubertal changes. Conclusions: Navigating the adaptations to the different aspects of T1D, from treatment to complications and adolescents' personal growth, effectively requires a thorough understanding of the barriers of a treatment regimen that patients at this critical age face.

The increasing global incidence of obesity and type 2 diabetes mellitus (T2D) underscores the urgency of addressing these interconnected health challenges. Obesity enhances genetic and environmental influences on T2D, being not only a primary risk factor but also exacerbating its severity. The complex mechanisms linking obesity and T2D involve adiposity-driven changes in β-cell function, adipose tissue functioning, and multi-organ insulin resistance (IR). Early detection and tailored treatment of T2D and obesity are crucial to mitigate future complications. Moreover, personalized and early intensified therapy considering the presence of comorbidities can delay disease progression and diminish the risk of cardiorenal complications. Employing combination therapies and embracing a disease-modifying strategy are paramount. Clinical trials provide evidence confirming the efficacy and safety of glucagon-like peptide 1 receptor agonists (GLP-1 RAs). Their use is associated with substantial and durable body weight reduction, exceeding 15%, and improved glucose control which further translate into T2D prevention, possible disease remission, and improvement of cardiometabolic risk factors and associated complications. Therefore, on the basis of clinical experience and current evidence, the Eastern and Southern Europe Diabetes and Obesity Expert Group recommends a personalized, polymodal approach (comprising GLP-1 RAs) tailored to individual patient's disease phenotype to optimize diabetes and obesity therapy. We also expect that the increasing availability of dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists will significantly contribute to the modern management of the cardiometabolic continuum.

This randomized, double-blind, placebo-controlled trial investigated the impact of 14-day Anaerobutyricum soehngenii L2-7 supplementation on postprandial glucose levels in 25 White Dutch males with type 2 diabetes (T2D) on stable metformin therapy. The primary endpoint was the effect of A. soehngenii versus placebo on glucose excursions and variability as determined by continuous glucose monitoring. Secondary endpoints were changes in ambulatory 24-h blood pressure, incretins, circulating metabolites and excursions of plasma short-chain fatty acids (SCFAs) and bile acids upon a standardized meal. Results showed that A. soehngenii supplementation for 14 days significantly improved glycemic variability and mean arterial blood pressure, without notable changes in SCFAs, bile acids, incretin levels, or anthropometric parameters as compared to placebo-treated controls. Although well-tolerated and effective in improving glycemic control in the intervention group, further research in larger and more diverse populations is needed to generalize these findings.

Insulin, an essential peptide hormone, conjointly regulates blood glucose levels by its receptor and it is used as vital drug to treat diabetes. This therapeutic hormone may undergo different chemical modifications during industrial processes, pharmaceutical formulation, and through its endogenous storage in the pancreatic β-cells. Insulin is highly sensitive to environmental stresses and readily undergoes structural changes, being also able to unfold and aggregate in physiological conditions. Even; small changes altering the structural integrity of insulin may have significant impacts on its biological efficacy to its physiological and pharmacological activities. Insulin analogs have been engineered to achieve modified properties, such as improved stability, solubility, and pharmacokinetics, while preserving the molecular pharmacology of insulin. The casually or purposively strategies of chemical modifications of insulin occurred to improve its therapeutic and pharmaceutical properties. Knowing the effects of chemical modification, formation of aggregates, and nanoparticles on protein can be a new look at the production of protein analogues drugs and its application in living system. The project focused on effects of chemical modifications and nanoparticles on the structure, stability, aggregation and their results in effective drug delivery system, biological activity, and pharmacological properties of insulin. The future challenge in biotechnology and pharmacokinetic arises from the complexity of biopharmaceuticals, which are often molecular structures that require formulation and delivery strategies to ensure their efficacy and safety.

New anti-diabetic medications, including glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors are recommended in guidelines to reduce cardio-renal events in type 2 diabetes mellitus (T2DM), independent of glucose control. Yet they might be underused in real world. This study aims to address the knowledge gap, prescription patterns and barriers faced by Chinese doctors. Cardio-Metabolic Survey was a cross-sectional study conducted among doctors managing diabetic patients in clinical practice, via a designated online questionnaire from May 1st, to Dec. 31th, 2022. A total of 358 doctors from 57 hospitals across Beijing participated in this survey, 34.9% from tertiary hospitals. Only 30-40% doctors demonstrated somewhat understanding of the mechanism and clinical applications of GLP-1RA or SGLT2 inhibitors. There is no difference in understanding of these two medications overall (p = 0.336). However, doctors in tertiary hospitals have a higher understanding of GLP-1RA and SGLT2 inhibitors compared to those in non-tertiary hospitals (p = 0.049, and 0.008, respectively). 40.2% doctors have never prescribed GLP-1RA, and 36.6% for SGLT2 inhibitors. The frequency of prescribing SGLT2 inhibitors was significantly higher than prescribing GLP-1RA (p = 0.005). The main barriers on prescription include high cost, poor adherence, side effects concern, and insufficient knowledge about these medications. Chinese doctors currently have limited understanding and low prescription frequency for GLP-1RA and SGLT2 inhibitors. Multifaceted approaches are needed to improve doctors' knowledge and strengthen their ability to manage T2DM effectively.

There is a critical knowledge gap in optimally combining transcranial magnetic stimulation (TMS) and antidepressants to treat patients with major depressive disorder (MDD). TMS is effective in treating MDD in patients who have failed at least one antidepressant trial, with accelerated protocols showing faster remission in treatment-resistant depression (TRD). Although clinicians routinely augment antidepressants with TMS, there is a knowledge gap in stopping versus continuing antidepressants or the dosing strategies when starting or tapering TMS. These considerations are important when considering maintenance TMS (delivered alone or in combination with suitable antidepressants) to maintain remission in MDD after the index course of TMS. As the first step towards filling this knowledge gap, we reviewed randomized controlled trials (RCTs) and open-label trials from 2 databases (PubMed/Medline and EMBASE) that compared active TMS combined with a pre-specified antidepressant dosed in the same manner for adults with MDD versus sham TMS combined with the same antidepressant as in the active arm. All studies were published between January 1, 2000, and December 31, 2023. We excluded case reports, case series, and clinical studies that augmented TMS with antidepressants and vice versa. We found 10 RCTs (n = 654 participants) and performed a meta-analysis. This showed active TMS combined with pre-specified antidepressants had greater efficacy for MDD treatment than sham TMS combined with the same antidepressants as in the active arm (Hedge's g = 1; 95 % CI [0.27, 1.73]). The review and meta-analysis indicate greater short-term efficacy in combining antidepressants with TMS from the get-go in MDD. Given the increasing role of accelerated TMS protocols in expediting remission in MDD and the results of our meta-analysis, we advocate for RCTs examining the short-term and long-term effects of various antidepressant classes on these TMS protocols in MDD. This can also optimize and individualize maintenance TMS protocols to prevent relapse in MDD.

The lack of effective treatments for dementia has led to explore the potential of antidiabetic agents as a possible approach. This cross-sectional and population-based study aimed to investigate the relationship between each antidiabetic drug and their defined daily doses (DDDs) and the use of anti-Alzheimer's disease (AD) drugs in order to establish new possible hypotheses about the role of antidiabetic drugs in AD. For that purpose, a database containing information on medications prescribed to 233183 patients aged 50 years or older between 2018 and 2020 was used. DDDs were calculated according to the ATC/DDD index 2023. Statistical analyses, with logistic regression, were carried out to assess antidiabetic and anti-AD drugs consumption. A total of 91836 patients who were prescribed at least one antihypertensive, antidiabetic, or lipid-modifying agent were included in the study; specifically, 29260 patients were prescribed antidiabetic medication. Among the antidiabetic agents, glucagon-like peptide-1 analogs (GLP-1) DDDs were likely to have a positive association with anti-AD drugs in people aged between 70 and 80 years. Additionally, sodium-glucose cotransporter 2 inhibitors (SGLT2i) were prone to have a positive association with anti-AD drug usage across almost every age. However, insulin usage was associated with an increased usage of anti-AD agents. In conclusion, there is evidence suggesting a correlation between certain antidiabetic agents and dementia. Specifically, GLP-1 and SGLT2i might be associated with lower odds of anti-AD drugs usage, while insulins might be linked to higher odds of using anti-AD drugs.

The influence of misconceptions and related socio-demographics on metformin use could hamper adherence to medications. This study aimed to assess the rates and causes of metformin non-adherence and to investigate knowledge, attitudes, and practices (KAP) on misconceptions of metformin use including the association with socio-demographic variables.

An observational analytical cross-sectional study was conducted at the diabetes clinic of Karapitiya Teaching Hospital in Galle, Sri Lanka. Causes of metformin non-adherence, associations with socio-demographics, and KAP on misconceptions on metformin use were assessed using the chi-squared test, t-tests, and ANOVA using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States) (p<0.05).

Metformin non-adherence was reported as 55%. Use of complementary and alternative therapies was 14.7%. Fear of major organ failure was the commonest (20.5%) reason quoted within the non-adherence group (N=223). Socio-demographic factors like ethnicity, lower education, unemployment, use of complementary and alternative therapies, and obtaining medications for other diabetes-related diseases significantly influenced adherence to the metformin-prescribed doses (p<0.05). Among all participants (N=400), the most common misconception was that long-term use of metformin caused organ damage (kidney 72.5%, liver 64.3%, and heart 34.8%), while 44% believed higher doses (two tablets or more for a day) caused organ damage. The KAP scores were reported as 24.5% with low, 52.7% moderate, and 22.7% satisfactory levels. Significantly lower KAP scores were associated with lower education levels and patients obtaining complementary and alternative therapies (p<0.05).

Misconceptions are not merely kept in mind but lead to non-adherence with metformin doses prescribed and warrant evidence-based educational interventions with the high-risk groups.

The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with an increased risk of gallbladder and bile duct disease among patients with type 2 diabetes.

We conducted a population-based cohort study using an active comparator, new-user design. We used data from the United Kingdom Clinical Practice Research Datalink to identify patients newly treated with either a DPP-4 inhibitor or sodium-glucose cotransporter-2 (SGLT-2) inhibitor between January 2013 and December 2020. We fitted Cox proportional hazards models with propensity score fine stratification weighting to estimate the hazard ratio (HR) and its 95% confidence interval (CI) for incident gallbladder and bile duct disease associated with DPP-4 inhibitors compared to SGLT-2 inhibitors.

DPP-4 inhibitors were associated with a 46% increased risk of gallbladder and bile duct disease (4.3 vs. 3.0 events per 1000 person-years, HR 1.46, 95% CI 1.17-1.83). At 6 months and 1 year, 745 and 948 patients, respectively, would need to be treated with DPP-4 inhibitors for one patient to experience a gallbladder or bile duct disease.

In this population-based cohort study, the use of DPP-4 inhibitors, when compared with SGLT-2 inhibitors, was associated with a moderately increased risk of gallbladder and bile duct disease among patients with type 2 diabetes. This outcome was still quite rare with a high number needed to harm at 6 months and 1 year.

The prevalence of overactive bladder (OAB) is known to be higher in patients with type 2 diabetes (T2DM). However, few studies have examined specific risk factors contributing to its progression among diabetes mellitus (DM) patients, so this study aimed to investigate the risk factors specific to diabetes mellitus that influence overactive bladder in the Syrian population. This cross-sectional study was conducted at four endocrinology centers in four Syrian provinces: Damascus, Aleppo, Homs, Hama, and Latakia. The study was comprised of patients who had been diagnosed with both T2DM and OAB and had visited these centers from February 2020 to January 2023. The Arabic version of the Overactive Bladder Symptom Score (OABSS) scale was used to categorize the participants based on the severity score into two groups: the mild OAB group and the moderate-severe OAB group. A logistic analysis was conducted to assess the risk factors associated with the OAB among patients with diabetes. Among the 153 patients diagnosed with both DM and OAB, significant distinctions were found between the two groups concerning the severity of overactive bladder, age, duration of diabetes, symptomatic diabetic peripheral neuropathy (DPN), and ankle reflex (P < 0.05). Furthermore, a multivariate analysis revealed that age (OR 1.48, 95% CI 0.89-2.19), duration of diabetes (OR 1.94, 95% CI 0.53-2.23), and symptomatic DPN (OR 2.74, 95% CI 1.39-4.13) independently acted as risk factors for the advancement of OAB. The severity of OAB in Syrian patients with diabetes is closely associated with the severity of DM. Factors such as age, duration of diabetes, and symptomatic DPN are independent predictors of the severity of OAB. Patients who experience symptomatic DPN are at an increased risk of developing OAB.