Cardiovascular Safety Profile of Semaglutide and Variations by Sex, Race, and Kidney Function: A Systematic Review and Meta-analysis

Background Patients with diabetes mellitus and its complications are at increased risk for cardiovascular diseases. Semaglutide is efficacious for glycemic control and reducing the risk of major adverse cardiovascular outcomes. Although trials have provided data about cardiovascular outcomes with this agent, a meta-analysis regarding its cardiovascular safety and variations in outcomes according to sex, race and estimated glomerular filtration rate was necessary. Materials and Methods We searched the PubMed, Cochrane Library, and Clinicaltrials.gov databases and included randomized controlled trials (RCTs) where semaglutide was the intervention and major adverse cardiovascular events (MACE) or expanded MACE was the outcome. We assessed the quality of the RCTs using the Cochrane Risk of Bias tool and used the statistical software RevMan 5.4. The protocol for this review was registered on PROSPERO (CRD42024580784). Results Of 5387 articles, four RCTs were included. The risk of MACE with semaglutide was significantly lower in patients with established or a risk of cardiovascular disease (risk ratio [RR] 0.81; 95% confidence interval [CI] 0.74-0.88; p < 0.00001). The risk of expanded MACE also reduced significantly with semaglutide (RR 0.80; 95% CI 0.75-0.86; p < 0.00001). MACE risk reduction was significant in males (RR 0.78; 95% CI 0.70-0.87; p < 0.00001) and in Asian (RR 0.61; 95% CI 0.44-0.83; p = 0.002) and white (RR 0.82; 95% CI 0.73-0.90; p = 0.0001) populations. Conclusion Semaglutide provides significant advantages in terms of lowering the risk of MACE and expanded MACE and could possibly be used as a crucial component of cardiovascular risk management, particularly in populations that respond well, such as men and Asian and white populations. RegistrationPROSPERO identifier number CRD42024580784.