SURPASS-CVOT reports: Mounjaro non-inferior to Trulicity on cardiovascular events

Eli Lilly reported topline results on July 31, 2025 from SURPASS-CVOT, the first cardiovascular outcomes trial to compare two incretin medicines head to head instead of against a placebo ^[1][2]. Tirzepatide (Mounjaro) met the trial's primary goal of non-inferiority against dulaglutide (Trulicity), an older GLP-1 drug with proven heart benefit, with an 8% lower rate of cardiovascular death, heart attack or stroke ^[1].

The trial randomized 13,299 adults with type 2 diabetes and established atherosclerotic cardiovascular disease 1:1 across 640 sites in 30 countries ^[1]. Participants received the maximum tolerated dose of Mounjaro (5 mg, 10 mg or 15 mg) or Trulicity 1.5 mg, both injected once weekly ^[1]. The study ran about five years, with a median follow-up of four years ^[1] — 210.1 weeks, according to a later Lilly release ^[2]. That makes it the largest and longest tirzepatide study to date ^[1].

What the numbers showed

For the primary endpoint, time to first major adverse cardiovascular event (MACE-3), the hazard ratio was 0.92 (95.3% confidence interval 0.83 to 1.01; p = 0.086) ^[1]. Because the upper limit of that interval fell below the prespecified boundary of 1.05, the trial met non-inferiority ^[1]. But the p-value of 0.086 means superiority was not established ^[2]. In plain terms: Mounjaro was shown to be at least as good as Trulicity on heart events, not clearly better.

Secondary results favored tirzepatide, though Lilly notes these were not controlled for multiplicity-adjusted type 1 error, which makes them supportive rather than definitive ^[1]. All-cause death was 16% lower with Mounjaro (hazard ratio 0.84; 95.0% CI 0.75 to 0.94; p = 0.002) ^[1]. In participants at high or very high risk of chronic kidney disease, eGFR declined 4.97 mL/min/1.73 m² with Mounjaro versus 8.51 with Trulicity at 36 months, a difference of 3.54 (95.0% CI 2.57 to 4.50) ^[1].

On metabolic measures, from a mean baseline A1C of 8.39%, Mounjaro cut A1C by 1.73% versus 0.90% for Trulicity at 36 months, a difference of 0.83 percentage points ^[1]. From a mean baseline weight of 92.6 kg (204.15 lbs), Mounjaro produced a 12.06% drop (25.20 lbs) compared with 4.95% (10.25 lbs) for Trulicity, a 7.1-point difference ^[1].

Side effects were mostly gastrointestinal and generally mild to moderate, occurring largely during dose escalation ^[1]. Discontinuation due to adverse events was 13.3% with Mounjaro versus 10.2% with Trulicity ^[1].

One caveat on interpretation: Lilly also reported a prespecified indirect comparison, matching patient-level data from SURPASS-CVOT and the older REWIND trial, which estimated Mounjaro reduced MACE-3 by 28% (hazard ratio 0.72) and all-cause death by 39% (hazard ratio 0.61) versus a "putative placebo" ^[1]. That is a modeled comparison, not a randomized one. Sources also differ slightly on enrollment framing: Lilly cites 13,299 randomized participants ^[1], while TCTMD described the trial as enrolling "more than 13,200 patients" ^[4].

Why it matters for patients

Most GLP-1 heart outcome trials compare a drug to placebo. This one set a higher bar by using an active comparator that already had a cardiovascular indication ^[2]. For people with type 2 diabetes and heart disease, the practical upshot is that tirzepatide preserved the heart protection seen with dulaglutide while producing larger A1C and weight reductions in the same trial ^[1].

What the trial did not show is that tirzepatide beats dulaglutide on heart events — the mortality and kidney findings, while striking, come with statistical caveats ^[1][2]. The slightly higher discontinuation rate for side effects is also worth knowing about ^[1].

What happens next

Full results were presented at the European Association for the Study of Diabetes annual meeting in September 2025 and published in a peer-reviewed journal ^[1][4]; Lilly later confirmed publication in The New England Journal of Medicine ^[2].

On August 28, 2026, the FDA approved Mounjaro to lower the risk of major adverse cardiovascular events — cardiovascular death, non-fatal heart attack or non-fatal stroke — in adults with type 2 diabetes at high risk for those events ^[2]. The trial data have also been added to Mounjaro's product information in the European Union ^[2].

Separately, SURMOUNT-MMO is testing tirzepatide in people with overweight and cardiovascular disease, with results not expected until 2027 ^[4].