Every Peptide

SURPASS-CVOT post hoc: broader cardiorenal outcomes favor tirzepatide vs dulaglutide

A post hoc analysis of SURPASS-CVOT expands the endpoint list beyond classic MACE. In patients with type 2 diabetes and established CVD, tirzepatide was associated with fewer composite cardiovascular + kidney events than dulaglutide, with more GI side effects.

Research Updates By Every Peptide Editorial Team

SURPASS-CVOT (the big head-to-head outcomes trial) previously reported that tirzepatide (a dual GLP-1/GIP receptor agonist) was noninferior to dulaglutide (a GLP-1 receptor agonist) for the classic “3-point MACE” composite (CV death, MI, stroke).

A new post hoc analysis asks a slightly different question: what happens if you look at a broader range of cardiovascular and kidney outcomes, bundled into a wider composite?

What this study is

  • post hoc analysis of a completed, randomized, double-blind trial (SURPASS-CVOT)
  • population: adults with type 2 diabetes + established cardiovascular disease
  • comparison: weekly tirzepatide (up to 15 mg) vs weekly dulaglutide (1.5 mg fixed dose)
  • follow-up: median ~47 months

What changed (the endpoint)

Instead of focusing only on MACE, the primary efficacy measure here was time to first event in a 6-component composite that included:

  • all-cause mortality
  • myocardial infarction
  • stroke
  • coronary revascularization
  • hospitalization for heart failure
  • a composite of adverse kidney outcomes

That expanded composite is clinically appealing (it’s closer to how real-world risk shows up), but it’s also why the word post hoc matters. When you expand endpoints after the fact, you can increase the chance of finding “something” that looks better.

What they found (top-line numbers)

In 13,165 participants:

  • composite events: 23.7% with tirzepatide vs 27.4% with dulaglutide
  • hazard ratio: 0.84 (95% CI 0.79 to 0.90)

They report similar effect sizes in sensitivity analyses using narrower composites.

What we know vs what we don’t

What we know reasonably well:

  • in this population, over nearly 4 years, the expanded composite was lower in the tirzepatide arm
  • GI adverse events were more common with tirzepatide (as expected for incretin therapies)

What’s still uncertain (and why):

  • this is a post hoc endpoint definition, so it is not the same evidentiary weight as a prespecified primary endpoint
  • the composite blends outcomes with different clinical “weights” and frequencies; composites can move even if the most serious components don’t
  • this analysis doesn’t automatically tell you which component(s) are driving the difference without drilling into the component-level results and adjudication details

Why it matters

We’re entering an era where the question is no longer just “how much weight loss,” but what happens to hard outcomes (heart failure, kidney events, mortality) when these drugs are used at scale and for longer durations.

A head-to-head outcomes trial is already high-signal. An expanded composite analysis is still useful, but it should be read as hypothesis-strengthening, not hypothesis-ending.

Source

Nissen SE, et al. Cardiorenal Outcomes With Tirzepatide Compared With Dulaglutide in Patients With Diabetes and Cardiovascular Disease: A Post Hoc Analysis of the SURPASS-CVOT Randomized Clinical Trial. JAMA Cardiology. (2026).

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