Sodium-glucose cotransporter 2 inhibitors and the risk of venous thromboembolism: A population-based cohort study.

AIMS: The cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) result from their complex impact on coronary and arterial vessels. However, their effect on veins and the risk of venous thromboembolism (VTE) remains unclear. Meta-analysis of trials has suggested no significant change in risk, but observational studies on the topic are scarce. Our objective was to determine if the use of SGLT2Is, compared to the use of dipeptidyl peptidase 4 inhibitors (DPP-4Is), is associated with the risk of VTE among patients with type 2 diabetes. METHODS: Using the Clinical Practice Research Datalink linked to hospitalization and vital statistics databases, we conducted a retrospective cohort study using a prevalent new-user design. SGLT2Is were matched to DPP-4I users on calendar time, diabetes treatment intensity, duration of previous DPP-4I use and time-conditional high-dimensional propensity score. Cox proportional hazard models estimated the hazard ratio (HR) for VTE with SGLT2Is versus DPP-4Is. RESULTS: SGLT2I use was not associated with an increased risk of VTE (HR 0.65, 95% confidence interval [CI] 0.34 to 1.25). This finding was consistent among prevalent (HR 0.47, 95% CI 0.16 to 1.42) and incident (HR 0.75, 95% CI 0.33 to 1.72) new users. CONCLUSIONS: We found that SGLT2Is were not associated with an increased risk of VTE compared to DPP-4Is. Although we observed a numerically decreased risk of VTE with SGLT2Is, estimates were accompanied by wide 95% CIs. Nonetheless, given the morbidity associated with VTE, our results provide some reassurance regarding the safety of SGLT2Is with respect to VTE.

Efficacy and Safety of Metformin for Obesity: A Systematic Review.

CONTEXT: The efficacy and safety of metformin for obesity in children and adolescents remains unclear. OBJECTIVE: To assess the efficacy and safety of metformin via systematic review. DATA SOURCES: Data sources included PubMed, Embase, the Cochrane Library, Scopus, and ClincalTrials.gov (inception to November 2019). STUDY SELECTION: We selected randomized controlled trials (RCTs) in which researchers assessed the efficacy and safety of metformin with lifestyle interventions, compared with a placebo with lifestyle interventions, in children and adolescents with obesity. DATA EXTRACTION: Two researchers independently extracted data and assessed quality. The primary outcomes were mean changes from baseline in BMI, BMI z score, homeostatic model assessment of insulin resistance, and gastrointestinal adverse effects. RESULTS: Twenty-four RCTs (1623 patients; range: 16 to 151) were included. Ages ranged from 4 to 19 years, and follow-up ranged from 2 months to 2 years. Metformin resulted in a modest decrease in BMI (range of mean values: -2.70 to 1.30 vs -1.12 to 1.90), BMI z score (range of mean values: -0.37 to -0.03 vs -0.22 to 0.15), and homeostatic model assessment of insulin resistance (range of mean values: -3.74 to 1.00 vs -1.40 to 2.66). Metformin resulted in a higher frequency of gastrointestinal adverse effects (range: 2% to 74% vs 0% to 42%). LIMITATIONS: The available evidence is of varying quality, with high heterogeneity between trials, suggesting some uncertainty in the benefits of metformin in this population. CONCLUSIONS: With this systematic review of RCTs, we suggest that metformin has modest but favorable effects on weight and insulin resistance and a tolerable safety profile among children and adolescents with obesity.