GLP-1 receptor agonists significantly reduce weight and cardiovascular events in high-risk populations, with limited direct thromboembolic evidence.
Background
Individuals with obesity and cardiometabolic disorders face an elevated risk of thromboembolic events. While Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established for weight loss and cardiovascular benefits, their direct impact on reducing thromboembolic risk in high-risk groups, including those with cancer, diabetes, and cardiovascular disease, remains incompletely understood. This systematic review aimed to synthesize existing evidence on GLP-1RAs' efficacy in these areas, addressing a critical knowledge gap for comprehensive patient management.
Study Design
Researchers conducted a systematic review following PRISMA 2020 guidelines, searching Scopus, PubMed, Cochrane Library, and Web of Science (WoS). They initially identified 110 records, ultimately including 8 studies for detailed analysis. Data extraction, risk of bias assessment, and narrative synthesis were independently conducted to evaluate the effects of GLP-1 receptor agonists on weight reduction, cardiovascular outcomes, and thromboembolic event risk in high-risk populations. The review focused on trials comparing GLP-1RAs against controls.
Results
GLP-1 receptor agonists consistently demonstrated greater weight reduction compared with controls across the included studies. Specifically, Semaglutide trials reported up to 15.2 % weight loss versus 2.6 % in controls (p < 0.0001), while Liraglutide showed approximately 5 % reduction versus no change. Cardiovascular outcome trials revealed significant risk reduction in major cardiovascular events. For instance, hazard ratios were 0.80 (0.72-0.90) and 0.74 (0.58-0.95), indicating a decreased risk. However, direct reporting on venous thromboembolism was limited; one study noted fewer events (1 vs 3) in the intervention group, though without statistical significance. Safety profiles were generally acceptable, with slightly increased gallbladder events (2.8 % vs 2.3 %), rare pancreatitis, and no consistent cancer risk observed. Serious adverse events were similar or lower in intervention groups (33.4 % vs 36.4 %).
Key Findings
- GLP-1RAs consistently achieved greater weight reduction compared to controls.
- Semaglutide trials reported up to 15.2 % weight loss vs. 2.6 % in controls (p < 0.0001).
- Liraglutide showed approximately 5 % weight reduction vs. no change.
- Cardiovascular outcome trials demonstrated significant major cardiovascular event risk reduction (HR 0.80 and 0.74).
- Direct venous thromboembolism reporting was limited, with one study showing fewer events (1 vs 3) without statistical significance.
Why It Matters
For individuals with diabetes, cardiovascular disease, or cancer, GLP-1RAs offer a dual benefit of substantial weight loss and reduced cardiovascular risk, reinforcing their role as a cornerstone therapy. While direct evidence for thromboembolic risk reduction remains nascent, the overall positive safety profile and MACE benefits suggest a broader protective effect. Clinicians should consider GLP-1RAs for comprehensive cardiometabolic management in these vulnerable populations, even as further large-scale studies are awaited to solidify the thromboembolic data. This review highlights the need for more targeted research into specific thrombotic outcomes to fully understand the complete risk-benefit profile.
glp-1-agonist
semaglutide
liraglutide
weight-loss
cardiovascular-disease
diabetes