Metformin improves insulin sensitivity in insulin sensitive tissues such as liver, muscle and fat. However, the functional roles and the underlying mechanism of metformin action in pancreatic β cells remain elusive. Here we show that, under normal growth condition, metformin suppresses MIN6 β cell proliferation and promotes apoptosis via an AMPK-dependent and autophagy-mediated mechanism. On the other hand, metformin protects MIN6 cells against palmitic acid (PA)-induced apoptosis. Our findings indicate that metformin plays a dual role in β cell survival and overdose of this anti-diabetic drug itself may lead to potential β cell toxicity.

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to global research to predict those who are at greatest risk of developing severe disease and mortality. The aim of this meta-analysis was to determine the associations between obesity and the severity of and mortality due to COVID-19. Methods: We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases for studies evaluating the associations of obesity with COVID-19. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Meta-regression analyses were conducted to estimate regression coefficients. Results: Forty-six studies involving 625,153 patients were included. Compared with nonobese patients, obese patients had a significantly increased risk of infection. (OR 2.73, 95% CI 1.53–4.87; I² = 96.8%), hospitalization (OR 1.72, 95% CI 1.55–1.92; I² = 47.4%), clinically severe disease (OR 3.81, 95% CI 1.97–7.35; I² = 57.4%), mechanical ventilation (OR 1.66, 95% CI 1.42–1.94; I² = 41.3%), intensive care unit (ICU) admission (OR 2.25, 95% CI 1.55–3.27; I² = 71.5%), and mortality (OR 1.61, 95% CI 1.29–2.01; I² = 83.1%). Conclusion: Patients with obesity may have a greater risk of infection, hospitalization, clinically severe disease, mechanical ventilation, ICU admission, and mortality due to COVID-19. Therefore, it is important to increase awareness of these associations with obesity in COVID-19 patients.

Whether the lipid profile in diabetic patients is associated with diabetic neuropathy (DN) development remains ambiguous, as does the predictive value of serum lipid levels in the risk of DN. Here, we performed the first meta-analysis designed to investigate the relationship between DN and the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL). Candidate studies were comprehensively identified by searching PubMed, Embase, Cochrane Library and Web of Science databases up to May 2020. Observational methodological meta-analysis was conducted to assess the relationships of TG, TC, HDL, and LDL levels with DN. Changes in blood lipids were used to estimate the effect size. The results were pooled using a random-effects or fixed-effects model. Potential sources of heterogeneity were explored by subgroup analysis. Various outcomes were included, and statistical analyses were performed using STATA (Version 12.0). Mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The Newcastle–Ottawa Scale (NOS) was applied to assess the methodological quality. I2 statistics were calculated to evaluate statistical heterogeneity. Funnel plots were utilized to test for publication bias. A sensitivity analysis was performed by omitting each study one by one. Thirty-nine clinical trials containing 32,668 patients were included in the meta-analysis. The results demonstrated that DN patients showed higher TG and lower HDL levels (MD = 0.34, 95% CI: 0.20–0.48 for TG; MD = -0.05, 95% CI: -0.08–-0.02, I² = 81.3% for HDL) than controls. Subgroup analysis showed that patients with type 1 diabetes mellitus (T1DM) neuropathy had elevated TG levels in their serum (MD = 0.25, 95% CI: 0.16–0.35,I² = 64.4% for T1DM). However, only patients with T1DM neuropathy had reduced serum HDL levels, and there was no significant difference in serum HDL levels between patients with T2DM neuropathy and controls (MD = -0.07, 95% CI: -0.10–-0.03, I² = 12.4% for T1DM; MD = -0.02, 95% CI: -0.07–0.03, I² = 80.2% for T2DM). TC and LDL levels were not significantly different between DN patients and controls (MD = -0.03, 95% CI: -0.14–0.09, I² = 82.9% for TC; MD = -0.00, 95% CI: -0.08–0.08, I² = 78.9% for LDL). In addition, compared with mild or painless DN patients, those with moderate or severe pain DN pain had significantly reduced serum TC and LDL levels (MD = -0.31, 95% CI: -0.49–-0.13, I² = 0% for TC; MD = -0.19, 95% CI: -0.32–-0.08, I² = 0% for LDL). TG levels and HDL levels did not vary considerably between patients with mild or painless DN and those with moderate or severe DN pain patients (MD = 0.12, 95% CI: -0.28–0.51, I² = 83.2% for TG; MD = -0.07, 95% CI:-0.14–0.01, I² = 58.8% for HDL). Furthermore, people with higher TG and LDL levels had higher risk of DN (OR = 1.36, 95% CI: 1.20–1.54, I² = 86.1% for TG and OR = 1.10, 95% CI: 1.02–1.19, I² = 17.8% for LDL). Conversely, high serum HDL levels reduced the risk of DN (OR = 0.85, 95% CI: 0.75–0.96, I² = 72.6%), while TC levels made no significant difference with the risk of DN (OR = 1.02, 95% CI: 1.00–1.04, I² = 84.7%). This meta-analysis indicated that serum lipid profile changes are among the biological characteristics of DN. Lipid levels should be explored as routine laboratory markers for predicting the risk of DN, as they will help clinicians choose appropriate therapies, and thus optimize the use of available resources.

Overweight and obesity pose serious health challenges for individuals and societies. This study aims to facilitate personalised treatment of obesity by summarising recent research on weight-loss pharmacotherapies, with a focus on their effects on weight reduction, cardiometabolic health, psychological outcomes, and adverse events. This systematic review and meta-analysis included searches of Web of Science, PubMed, and Cochrane Central Register of Controlled Trials from inception to June 8, 2024. Randomised controlled trials evaluating weight-loss pharmacotherapies approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMA) for treating overweight or obesity were included. Primary outcomes included changes in body weight, cardiometabolic indicators, psychological outcomes, and adverse events. Summary data was extracted from published reports. Random-effects meta-analyses were used to calculate weighted mean differences (WMDs), risk ratios (RRs), and 95% confidence intervals (CI). The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used to assess the certainty of evidence for each pooled analysis. PROSPERO registration: CRD42024547905. A total of 154 randomised controlled trials (n = 112,515 participants) were included. Tirzepatide had the greatest weight-loss effect (WMD −11.69, 95% CI −19.22 to −4.15; P = 0.0024; I² = 100.0%; moderate certainty), followed by semaglutide (−8.48, −12.68 to −4.27; P < 0.0001; I² = 100.0%; moderate certainty). Tirzepatide had the strongest antihypertensive effect on both systolic (WMD −5.74, −9.00 to −2.48; P = 0.0006; I² = 99.8%; moderate certainty) and diastolic blood pressure (WMD −2.91, −4.97 to −0.85; P = 0.0056; I² = 99.8%; moderate certainty) and best reduced triglycerides (WMD −0.77, −0.85 to −0.69; P < 0.0001; I² = 3.2%; high certainty), fasting glucose (WMD −3.06, −5.53 to −0.59; P = 0.015; I² = 100.0%; moderate certainty), insulin (WMD −4.91, −8.15 to −1.68; P = 0.0029; I² = 97.0%; moderate certainty), and glycated haemoglobin levels (WMD −1.27, −1.82 to −0.73; P < 0.0001; I² = 100.0%; moderate certainty). Semaglutide (RR 0.83, 0.74–0.92; P < 0.0001; I² = 0.0%; high certainty) and liraglutide (0.87, 0.79–0.96; P = 0.0059; I² = 0.0%; high certainty) reduced the risk of major adverse cardiovascular events (MACEs). However, all three medications were associated with adverse gastrointestinal effects. Naltrexone/bupropion increased the risk of elevated blood pressure (RR 1.72, 1.04–2.85; P = 0.036; I² = 0.0%; high certainty). Topiramate increased depression risk (RR 1.62, 1.14 to 2.30; P = 0.0077; I² = 0.0%; high certainty), and phentermine/topiramate raised concerns about anxiety (RR 1.91, 1.09 to 3.35; P = 0.025; I² = 29.5%; high certainty), sleep disorders (RR 1.55, 1.24–1.93; P < 0.0001; I² = 0.0%; high certainty), and irritability (RR 3.31, 1.69–6.47; P < 0.0001; I² = 0.0%; high certainty). No medication increased the risk of serious adverse events. For weight reduction, tirzepatide is the top choice, followed by semaglutide. Considering cardiometabolic risk factors, tirzepatide shows the best blood pressure- and glucose-lowering benefits, while semaglutide and liraglutide reduce the risk of MACEs. Naltrexone/bupropion carries a risk of increased blood pressure. Phentermine/topiramate should be used with caution due to its higher risk of psychological side effects. Despite limitations related to study heterogeneity, these findings provide valuable insights for weight management strategies across diverse individuals. 10.13039/501100001809 National Natural Science Foundation of China , Leading Talents Program of Hunan Province, and 10.13039/501100012476 Fundamental Research Funds for the Central Universities of Central South University .

Background: Hyperglycemia at admission has been demonstrated to exacerbate the outcomes of coronavirus disease 2019 (COVID-19) but a meta-analysis is lacking to further confirm this hypothesis. The purpose of this meta-analysis was to summarize the evidence on the association between hyperglycemia at admission and the development of COVID-19. Method: Four databases namely, PubMed, Web of Science, Embase and Cochrane Library, were screened for eligible studies. STATA software was utilized to pool data for this meta-analysis. The primary outcomes included mortality and severity. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with random-effects models, and the quality of evidence was appraised by the Newcastle–Ottawa Scale (NOS). This meta-analysis was prospectively registered online on PROSPERO, CRD42020191763. Results: Sixteen observational studies with 6386 COVID-19 patients relating hyperglycemia at admission to COVID-19 outcomes were included. The overall data demonstrated that, compared with the control, the hyperglycemia at admission group was more likely to have increased mortality (OR = 3.45, 95% CI, 2.26–5.26) and severe/critical complications (OR = 2.08, 95% CI, 1.45–2.99) of COVID-19. Conclusion: Hyperglycemia at admission in COVID-19 patients may be a strong predictor of mortality and complications.

Aims: DPP-4 inhibitors are predicted to exert a protective effect on the progression of coronavirus disease 2019 (COVID-19). We conducted this meta-analysis to investigate this hypothesis.Methods: Four databases, namely, PubMed, Web of Science, EMBASE and the Cochrane Library, were used to identify studies on DPP-4 and COVID-19. The outcome indicators were the mortality of COVID-19. Funnel plots, Begg’s tests and Egger’s tests were used to assess publication bias.Results: Four articles were included with a total of 1933 patients with COVID-19 and type 2 diabetes. The use of DPP-4 inhibitors was negatively associated with the risk of mortality (odds ratio (OR) = 0.58 95% confidence interval (CI), 0.34–0.99).Conclusions: DPP-4 inhibitors may improve the mortality of patients with COVID-19 and type 2 diabetes. As few relevant studies are available, more large-scale studies need to be performed.