Sex differences in trial representation and the cardiovascular effectiveness of newer glucose-lowering agents in patients with and without type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials
Abstract
Aims: The extent to which the cardiovascular benefits of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) differ by sex remains unclear. This systematic meta-analysis aimed to investigate sex differences in trial representation and the cardiovascular and kidney efficacy of SGLT-2is and GLP-1RAs in patients with and without type 2 diabetes (T2D).
Materials and methods: Cardiovascular outcome trials (CVOTs) were identified through searches in MEDLINE, Embase, and CENTRAL, and manual search of ClinicalTrials.gov up to August 2025. Sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Sex-differential treatment effects were assessed using the ratio of HRs and meta-regression.
Results: Across 47 articles from 25 unique CVOTs (n > 185 000) published between 2015 and 2025, women were less represented (approximately one-third of trial participants). SGLT-2is and GLP-1RAs significantly reduced cardio-kidney outcomes in both men and women. In individuals with T2D, SGLT-2is significantly reduced risks of major adverse cardiovascular events (MACE) 0.87 (0.80-0.95) and composite cardiovascular death or hospitalization for heart failure 0.73 (0.64-0.83) in men, with broadly similar results for women and also for both sexes in individuals without T2D. In individuals with T2D, GLP-1RAs reduced MACE risk in men 0.89 (0.82-0.96) and women 0.83 (0.77-0.91). Pooled ratio…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
Read the paper
Related studies
- Risk Factors for Coronavirus Disease 2019 (COVID-19) Death in a Population Cohort Study from the Western Cape Province, South Africa
- Global and regional estimates of genital human papillomavirus prevalence among men: a systematic review and meta-analysis
- A methodology for assessing deployment trauma and its consequences in OEF/OIF/OND veterans: The TRACTS longitudinal prospective cohort study
- Post‑COVID‑19 Syndrome in Outpatients: a Cohort Study
- Factors Influencing Primary and Secondary Implant Stability—A Retrospective Cohort Study with 582 Implants in 272 Patients
- Electroacupuncture for Painful Diabetic Peripheral Neuropathy: A Multicenter, Randomized, Assessor-Blinded, Controlled Trial
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.