Cardiovascular outcomes of glucagon-like peptide-1 receptor agonists: A systematic review.
Nicoline Bihelek, Sarah Burke, Arden R Barry
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In 30 seconds
This systematic review evaluated 12 cardiovascular outcome-based randomised controlled trials of GLP-1 receptor agonists (GLP1RAs): 10 in people with type 2 diabetes (T2D), one in people with overweight or obesity and atherosclerotic cardiovascular disease (ASCVD) without T2D, and one in people with obesity and heart failure with preserved ejection fraction (HFpEF). GLP1RA therapy consistently reduced major adverse cardiovascular events (MACE) in T2D. Benefits were also observed in the two additional populations, although effects on cardiovascular and all-cause death were less certain. Gastrointestinal adverse events commonly led to treatment discontinuation.
Key findings
- Across trials in T2D, GLP1RA therapy consistently reduced MACE; effects on cardiovascular and all-cause death were less certain.
- In overweight or obesity with ASCVD but without T2D, weekly subcutaneous semaglutide lowered MACE risk but not cardiovascular death.
- In obesity with HFpEF, with or without T2D, tirzepatide lowered the composite of adverse heart failure events and cardiovascular death.
- Only liraglutide individually demonstrated reductions in MACE, cardiovascular death, and all-cause death.
Why it matters
The review brings together cardiovascular outcome evidence across populations with and without T2D. It indicates that GLP1RA-associated cardiovascular benefit may extend beyond T2D, while distinguishing reductions in MACE from less certain effects on mortality. Gastrointestinal adverse events leading to discontinuation are also relevant when weighing treatment tolerability.
What to keep in mind
The review reports that cardiovascular and all-cause mortality effects were less certain; the evidence in populations without T2D came from only two trials.