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Using GLP-1s

Cardiovascular outcomes trial (CVOT)

A large, multi-year randomized trial designed to test whether a drug changes the rate of heart attacks, strokes, and cardiovascular death. It is the type of study behind the GLP-1 heart-protection claims.

By the glp1.how editorial teamReviewed

A cardiovascular outcomes trial (CVOT) is a randomized study (usually thousands of participants followed for several years) whose primary question is whether a medication changes the rate of real cardiovascular events (MACE). A better number on A1c or body weight can't answer that question on its own. The FDA began requiring CVOTs for new diabetes drugs in 2008 after safety concerns with an earlier medication, which is why every major GLP-1 has one.

CVOTs are the reason the heart-benefit claims for GLP-1s carry weight: LEADER (liraglutide), SELECT (semaglutide in obesity without diabetes), REWIND (dulaglutide), and SURPASS-CVOT (tirzepatide versus dulaglutide) are all CVOTs. Because these trials enroll people at high cardiovascular risk, their results apply most directly to that group. See the cardiovascular benefits of GLP-1 medications.

The FDA replaced its 2008 guidance with a new draft in March 2020, noting that none of the completed CVOTs had found an increased risk of heart attack or stroke and some had shown a reduction (FDA draft guidance (external link)).

cvotcardiovascularclinical-trialsevidence

Revision history

Updated 2 times since Sep 2, 2026 · show changes
  1. v3

    Body revised

  2. v2

    Summary rewritten; Body revised; Metadata updated

  3. v1

    Change tracking began

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  • The cardiovascular benefits of GLP-1 medications · Several GLP-1 medications have been tested in large cardiovascular outcomes trials, and they lowered the combined rate of heart attack, stroke and cardiovascular death. The pooled data show clear drops in cardiovascular death, heart attacks and heart failure, but not a clear drop in stroke. What the trials found, who was in them, and what they don't tell you.
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Related terms

  • 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.
  • MACE (major adverse cardiovascular events) · A composite trial endpoint bundling cardiovascular death, non-fatal heart attack, and non-fatal stroke into a single outcome.
  • 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.

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