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Using GLP-1s

MACE (major adverse cardiovascular events)

The composite endpoint used in cardiovascular trials — usually cardiovascular death, non-fatal heart attack, and non-fatal stroke — that GLP-1 medications like semaglutide and liraglutide have been shown to reduce.

By the glp1.how editorial teamReviewed

MACE stands for "major adverse cardiovascular events." It is a composite endpoint (a bundle of outcomes counted together) that cardiovascular trials use as their primary measure. The standard "3-point MACE" combines cardiovascular death, non-fatal heart attack, and non-fatal stroke; some trials add hospitalization for unstable angina or heart failure to make a broader version.

When you read that a GLP-1 "reduced MACE by 20%," it means participants on the drug had those events at about 80% of the rate seen with placebo over the course of the trial, a hazard ratio of 0.80 (the SELECT result for semaglutide). Semaglutide (SELECT), liraglutide (LEADER), and dulaglutide (REWIND) have each shown MACE reductions, and tirzepatide was shown non-inferior to dulaglutide on MACE in SURPASS-CVOT. That result led the FDA to approve a cardiovascular risk-reduction indication for Mounjaro (tirzepatide) in adults with type 2 diabetes in August 2026 (Lilly (external link)). See the cardiovascular benefits of GLP-1 medications.

In SELECT, 6.5% of people on semaglutide and 8.0% on placebo had a 3-point MACE event, a hazard ratio of 0.80 (NEJM (external link)).

macecardiovascularclinical-trialsheart-health

Revision history

Updated 3 times since Sep 2, 2026 · show changes
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    Body revised

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Related terms

  • Hazard ratio · A statistic from clinical trials that compares how often an event happens over time in one group versus another; below 1 means a lower rate in the treated group.
  • GLP-1 · A gut hormone (glucagon-like peptide-1) that stimulates insulin release, slows digestion, and reduces appetite; the target of drugs like semaglutide and liraglutide.
  • Tirzepatide · A once-weekly dual GIP and GLP-1 receptor agonist made by Eli Lilly, marketed as Mounjaro for type 2 diabetes and Zepbound for weight management and obstructive sleep apnea.
  • Liraglutide · A first-generation GLP-1 receptor agonist taken as a daily injection, sold as Victoza for type 2 diabetes and Saxenda for weight management, and now also as a US generic.
  • Semaglutide · A GLP-1 receptor agonist medication made by Novo Nordisk, sold under the brand names Ozempic (type 2 diabetes) and Wegovy (weight management), each as an injection or a pill.
  • Mounjaro · Eli Lilly's brand name for injectable tirzepatide, FDA-approved for type 2 diabetes (adults and children 10+) and for cardiovascular risk reduction in high-risk adults with type 2 diabetes.
  • Cardiovascular outcomes trial (CVOT) · A large randomized trial built specifically to measure a drug's effect on heart attacks, strokes, and cardiovascular death, as opposed to surrogate markers like blood sugar or weight.

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