Novo real-world analysis at EASD links escalating to Ozempic 2 mg with 6% lower cardiovascular risk than switching to Mounjaro

Novo Nordisk presented a retrospective real-world analysis at the European Association for the Study of Diabetes (EASD) annual meeting in Milan on September 29, 2026, reporting that adults with type 2 diabetes taking once-weekly semaglutide (Ozempic) 1 mg who increased to 2 mg had a statistically significant 6% lower risk of major adverse cardiovascular events than similar patients who switched to tirzepatide (Mounjaro) at doses up to 15 mg ^[1][2].

The endpoint, called MACE, combined all-cause death, heart attack and stroke. Novo reported an adjusted hazard ratio of 1.06 (95% CI 1.04–1.08; P=0.005) ^[1]. In a subgroup of patients who had more than one HbA1c and/or weight measurement at baseline, results were similar: adjusted HR 1.07 (95% CI 1.01–1.13; P<0.035) ^[1]. The company did not release absolute event counts or event rates for either group, so how many additional heart attacks, strokes or deaths this 6% difference represents has not been disclosed ^[1].

What the study looked at

The analysis, called COMPETE SWITCH CV, used Komodo Health's Healthcare Map, a large US insurance claims database with linked lab results, covering January 2018 through September 2025 ^[1]. It started with 636,525 adults with type 2 diabetes who filled a prescription for semaglutide 1 mg ^[1][2].

Within 365 days of that first fill, 67.2% had stayed on 1 mg, 29.2% had escalated to semaglutide 2 mg, and 3.6% had switched to tirzepatide ^[1][2]. By 720 days, 57.4% were still on 1 mg, 36.9% had moved to 2 mg, and 5.7% had switched to tirzepatide ^[1][2]. Among those who switched, clinicians could titrate the dose after starting at 2.5 mg or 5 mg, and about 31% reached 10 mg or higher during follow-up ^[1].

The cardiovascular portion of the study compared 185,705 adults who escalated to semaglutide 2 mg with 23,104 adults who switched to tirzepatide, using an intention-to-treat approach and following them from the point of escalation or switching ^[1]. Safety outcomes were not assessed in this analysis ^[1]. The findings build on an earlier analysis of the same data on HbA1c and weight loss, presented at the American Diabetes Association Scientific Sessions in New Orleans in June 2026 ^[1].

The limits

This was not a head-to-head randomized trial. Novo's own release notes that real-world analyses may reflect residual unmeasured confounding, that associations do not establish cause and effect, and that retrospective claims data can exclude people with intermittent insurance coverage or underserved populations, limiting how broadly results apply ^[1]. The comparison groups were also very different in size — roughly eight escalators for every switcher — and the reasons a doctor chooses to raise a dose rather than change drugs may themselves relate to a patient's health.

The data are cited as Novo Nordisk "data on file" ^[1]. Whether the full analysis has been peer reviewed or published in a journal has not been reported.

Lilly brought competing datasets to the same meeting. It used indirect comparisons — also not head-to-head trials — to argue that its oral GLP-1 Foundayo (orforglipron) 17.2 mg produced 1.5% to 2.4% greater weight loss and 0.3% to 0.6% greater A1C reduction than oral semaglutide 25 mg, and that Zepbound (tirzepatide) 10 mg and 15 mg were tied to more weight loss than Wegovy HD (semaglutide 7.2 mg) ^[2]. In the Surmount-5 head-to-head trial that read out in late 2024, Zepbound produced 47% greater relative weight loss than Wegovy at 72 weeks, with average losses of 50.3 pounds versus 33.1 pounds ^[2].

Why it matters for patients

Many people on semaglutide 1 mg eventually face a fork in the road: go up to 2 mg, or change to a different drug. This analysis is one data point about what happens to heart outcomes after that choice, drawn from actual US claims rather than a controlled trial. Because it is observational and sponsored by the maker of one of the two drugs, it cannot settle which option is better for any individual.

It is also worth noting what the analysis did not cover: side effects and tolerability were not measured ^[1], and MACE is a different question from weight loss or blood sugar control, where tirzepatide has shown an edge in a randomized comparison ^[2]. Semaglutide injection carries a boxed warning for possible thyroid tumors, including cancer, and is not for people with a personal or family history of medullary thyroid carcinoma or MEN2; common side effects include nausea, vomiting, diarrhea, abdominal pain and constipation ^[1].

What happens next

The COMPETE SWITCH CV results were scheduled as a short oral discussion (LBA44) at EASD on September 29, 2026 ^[3]. No head-to-head randomized trial comparing semaglutide 2 mg with tirzepatide on cardiovascular outcomes has been announced.