Cardiovascular benefits of semaglutide: a systematic review and meta-analysis of randomized controlled trials

Semaglutide, a GLP-1 receptor agonist (GLP-1RA), has shown potential in controlling type 2 diabetes due to their ability to lower blood glucose and improve cardiovascular outcomes. Although semaglutide is the newest GLP-1RA available, its cardiovascular effects have not yet been systematically reviewed.

This meta-analysis adhered to a pre-registered protocol (PROSPERO ID: CRD42024538847). PubMed, Scopus, and Web of Science were searched comprehensively on February 26, 2024, to locate randomized controlled trials (RCTs) assessing semaglutide's impact on cardiovascular outcomes. A random effects model was used to analyze the data and the Cochrane risk of bias 2 tool was used to assess the quality of included studies.

There were four RCTs involving 27,617 individuals (13,809 receiving semaglutide and 13,808 receiving placebo). There was a significant reduction in the risk of major adverse cardiovascular events (MACE) after administration of semaglutide (RR: 0.81, 95% CI: 0.74-0.88, p < 0.001, I²: 0.00%). Additionally, benefits were observed for particular findings such as cardiovascular death and nonfatal myocardial infarction. However, semaglutide showed no significant effect on nonfatal stroke, heart failure hospitalizations, or admissions for unstable angina. The treatment also led to fewer serious adverse events (RR: 0.91, 95% CI: 0.88-0.94, p < 0.001, I²: 0.01%), though it was linked to a higher rate of treatment discontinuation (RR: 1.67, 95% CI: 1.27-2.21, p < 0.001, I²: 91.09%), which was underemphasized in its clinical implications and should be interpreted more cautiously considering the trade-off with benefits.

Semaglutide effectively reduces the risk of MACE and modestly improves cardiovascular mortality rates and nonfatal myocardial infarction, without significantly affecting nonfatal stroke incidence and hospitalizations (for angina and heart failure). While it lowers the occurrence of serious adverse events, it also increases the likelihood of discontinuing treatment.