Lilly announces SURPASS-CVOT topline: non-inferior on heart events, 16% lower all-cause death

Eli Lilly announced topline results on July 31, 2025, from SURPASS-CVOT, a head-to-head cardiovascular outcomes trial comparing tirzepatide (sold as Mounjaro for type 2 diabetes) with dulaglutide (Trulicity) in adults who have type 2 diabetes and established atherosclerotic cardiovascular disease ^[1]. Tirzepatide met the trial's main goal by showing it was not worse than dulaglutide at preventing major adverse cardiovascular events, and it was also linked to a 16% lower rate of death from any cause ^[1].

What the trial measured

SURPASS-CVOT randomized 13,299 participants 1:1 across 640 sites in 30 countries, and ran roughly five years with a median follow-up of four years ^[1]. Lilly calls it the largest and longest tirzepatide study to date ^[1]. Participants took the maximum dose of tirzepatide they could tolerate — 5 mg, 10 mg or 15 mg once weekly — or dulaglutide 1.5 mg once weekly ^[1].

The comparison choice matters. Instead of a placebo, Lilly used dulaglutide, a GLP-1 drug that had already shown a cardiovascular benefit against placebo in the 2019 REWIND trial ^[1]. That makes the primary question "is tirzepatide at least as good as a drug already known to help?" rather than "does tirzepatide beat nothing?"

The numbers

For the primary endpoint — time to first cardiovascular death, heart attack or stroke (MACE-3) — the hazard ratio was 0.92 (95.3% confidence interval 0.83 to 1.01; p = 0.086) ^[1]. That is an 8% lower rate that cleared the prespecified non-inferiority bar of an upper confidence limit below 1.05, but it did not reach statistical significance for superiority ^[1]. Lilly reported consistent results across all three components of the composite ^[1].

All-cause death was 16% lower with tirzepatide (hazard ratio 0.84; 95.0% CI 0.75 to 0.94; p = 0.002) ^[1]. Important caveat: Lilly states this endpoint, along with the kidney, A1C and weight results, was not controlled for multiplicity-adjusted type 1 error ^[1]. In plain terms, when many outcomes are tested, some differences can appear by chance, so these findings are considered supportive rather than definitive.

On other measures at 36 months: A1C fell 1.73% with tirzepatide versus 0.90% with dulaglutide from a shared mean baseline of 8.39%, a difference of −0.83% ^[1]. Body weight fell 12.06% (11.43 kg / 25.20 lbs) versus 4.95% (4.65 kg / 10.25 lbs) from a mean baseline of 92.6 kg (204.15 lbs), a 7.1-point difference ^[1]. In participants at high or very-high risk of chronic kidney disease, eGFR declined 4.97 versus 8.51 mL/min/1.73 m², a difference of 3.54 mL/min/1.73 m² favoring tirzepatide ^[1].

A prespecified indirect comparison using matched patient-level data from REWIND and SURPASS-CVOT estimated tirzepatide cut MACE-3 by 28% (HR 0.72; 95.0% CI 0.55 to 0.94) and all-cause death by 39% (HR 0.61; 95.0% CI 0.45 to 0.82) versus a "putative placebo" ^[1]. That is a modeled estimate, not a direct placebo comparison ^[1].

On safety, Lilly said the profiles for both drugs were generally consistent with what is already known, with gastrointestinal side effects most common, generally mild to moderate, and mostly resolving after dose escalation finished ^[1]. Discontinuation due to adverse events was 13.3% with tirzepatide versus 10.2% with dulaglutide ^[1].

Why it matters for patients

For people with type 2 diabetes and existing heart disease, the practical question has been whether tirzepatide's larger effects on blood sugar and weight come with the same cardiovascular protection already documented for some GLP-1 drugs. These topline results suggest tirzepatide preserved that protection rather than trading it away ^[1]. Lilly frames the findings as supporting Mounjaro as a "potential front-line treatment" for this group ^[1] — that is the company's characterization, and labeling decisions rest with regulators.

The mortality signal is the headline-grabbing number, but the statistical caveat is real: it was not adjusted for multiple comparisons ^[1]. The higher discontinuation rate for side effects also gives a sense of the tolerability trade-off in a long trial ^[1].

What is not yet known from this announcement: full adverse event tables, subgroup breakdowns, and event counts behind each hazard ratio. These results are also in people with type 2 diabetes and established cardiovascular disease, not the broader population using tirzepatide as Zepbound for obesity ^[1]. Studies of tirzepatide in chronic kidney disease and in obesity-related morbidity and mortality are still ongoing ^[1].

What happens next

Detailed results are set to be presented at the European Association for the Study of Diabetes annual meeting in September 2025 and published in a peer-reviewed journal ^[1]. Lilly says it plans to submit the data to global regulators by the end of 2025 ^[1].