At the European Society of Cardiology (ESC) Congress 2024, results were presented for a meta-analysis on the cardiovascular outcomes of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with obesity without diabetes mellitus. The effects of GLP-1RAs on cardiovascular outcomes in patients with diabetes mellitus have been studied extensively, but their cardioprotective effects in patients with obesity are yet to be substantiated.
A total of 19 randomised controlled trials (RCTs) were retrieved from PubMed, Cochrane, Scopus, and Web of Science up to December 26, 2023. Data on 32,884 patients was gathered to synthesize a systematic review and meta-analysis, which was conducted using StataMP 17. Cardiovascular outcomes, including changes in symptoms relating to heart failure and death from cardiovascular causes, were the primary outcomes of the study.
In results presented at the ESC conference by Mohamed Abouzid, Poznan University of Medical Sciences, with regards to efficacy and safety, cardiovascular mortality was the same among patients who received GLP-1RAs and patients who received placebo (risk ratio [RR] 0.85, 95% confidence interval [CI] 0.71–1.01, p = 0.07), while the incidence of all-cause mortality (RR 0.83, 95% CI 0.72–0.94, p < 0.0001), non-cardiovascular mortality (RR 0.78, 95% CI 0.63–0.96, p = 0.02), and myocardial infarction (MI) (RR 0.73, 95% CI 0.62–0.87, p < 0.0001) was significantly decreased with the use of GLP-1RAs. The incidence of adverse events (AEs) increased significantly with GLP-1RAs (RR 1.11, 95% CI 1.05–1.16, p < 0.0001), but the incidence of serious adverse events (SAEs) did not.
Thus, this study proved that GLP-1Ras offer significant benefits in lowering cardiovascular risks, namely reducing all-cause mortality and risk of MI, while also promoting weight loss, bettering lipid profiles, and enhancing blood pressure control. Nonetheless, GLP-1RAs are generally associated with an increased incidence of gastrointestinal side effects and heterogeneity in outcomes, emphasising the importance of personalised treatment approaches.
Key opinion leaders (KOLs) interviewed by GlobalData expressed that “you [have] got to make sure that you show that you are not just improving the weight of the patients, but you are improving the health of the patients [too]. So, you do have to look at the diabetes, and hypertension, and lipids…and you do have to look at the cardiovascular disease outcome [too].” According to GlobalData’s Pharma Intelligence Center, there are 20 Phase III candidates, 59 Phase II candidates, and 96 Phase I candidates for obesity globally.
