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SURPASS-CVOT: Tirzepatide Passes Cardio Outcomes Trial

SURPASS-CVOT confirms tirzepatide noninferior to dulaglutide for MACE in T2D with ASCVD — HR 0.92. Superiority missed by a narrow margin.

May 19, 2026 · 2 min read

Eli Lilly's pivotal cardiovascular outcomes trial for tirzepatide — SURPASS-CVOT — was published in the New England Journal of Medicine on December 18, 2025, confirming the drug's noninferiority to dulaglutide for major adverse cardiovascular events (MACE) in adults with type 2 diabetes and established atherosclerotic cardiovascular disease. Superiority was not demonstrated, though the point estimate favored tirzepatide.

What happened

SURPASS-CVOT enrolled adults with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) — patients with a prior myocardial infarction, stroke, or documented coronary/peripheral arterial disease. Participants were randomized to tirzepatide (titrated up to 15 mg weekly) or dulaglutide (1.5 mg weekly).

The primary endpoint was a composite of death from cardiovascular causes, nonfatal MI, or nonfatal stroke.

Results:

  • Tirzepatide: 12.2% of patients had a primary-endpoint event
  • Dulaglutide: 13.1% had a primary-endpoint event
  • Hazard ratio: 0.92 (95.3% CI: 0.83–1.01)
  • P=0.003 for noninferiority ✓
  • P=0.09 for superiority ✗

The trial met its noninferiority criterion by a wide margin. Superiority missed significance at the 0.05 threshold — the confidence interval just crossed 1.0 at the upper bound.

Secondary endpoints showed tirzepatide outperforming dulaglutide on weight loss (approximately 10 percentage points more), HbA1c reduction, and blood pressure. The all-cause mortality point estimate also favored tirzepatide, though individual secondary outcomes were not powered for formal inference in most cases.

Why it matters

SURPASS-CVOT fills a critical gap in tirzepatide's evidence base. Semaglutide has the LEADER trial (diabetes) and SELECT trial (obesity without diabetes) — both demonstrating cardiovascular benefit. Tirzepatide had no equivalent dataset until now.

The noninferiority result means tirzepatide does not increase cardiovascular risk relative to dulaglutide, which had already demonstrated cardiovascular safety in REWIND. The near-miss on superiority reflects a numerically favorable HR (0.92), but the trial wasn't powered for superiority with this event rate — a pre-planned acknowledgment in the study design.

For patients with T2D and ASCVD who are choosing between a GLP-1 agonist and tirzepatide, SURPASS-CVOT removes cardiovascular risk as a concern with tirzepatide and puts both drugs on similar cardiovascular footing. The choice can now turn more cleanly on efficacy, tolerability, and cost.

For more on how tirzepatide and semaglutide compare for patients with T2D, see tirzepatide for T2D vs. weight loss and the head-to-head comparison.

What to watch

Lilly is also running a cardiovascular outcomes trial in the obesity-without-diabetes population (SURMOUNT-MMO), mirroring Novo Nordisk's SELECT trial for semaglutide. SURMOUNT-MMO results are expected in 2026–2027. A positive SURMOUNT-MMO result would extend tirzepatide's cardiovascular indication beyond T2D — the commercial and clinical significance of that outcome for Zepbound would be substantial.

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