Plainsboro, New Jersey, U.S., and Bagsværd, Denmark, September 29, 2026
Novo Nordisk announced new real-world evidence showing that adults with type 2 diabetes who increased their once-weekly Ozempic® (semaglutide) injection from 1 mg to 2 mg were associated with a statistically significant 6% lower risk of major adverse cardiovascular events (MACE) compared with patients who switched to Mounjaro® (tirzepatide) at doses up to 15 mg. The findings were presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2026 in Milan, Italy. The retrospective analysis included 636,525 adults with type 2 diabetes and provides additional real-world insight into treatment-intensification strategies for patients already receiving semaglutide.
Large Real-World Analysis Examines Treatment Changes
The COMPETE SWITCH Cardiovascular study used retrospective healthcare claims data to examine treatment patterns among adults with type 2 diabetes who were receiving semaglutide 1 mg. Researchers compared patients who escalated to semaglutide 2 mg with those who switched to tirzepatide, evaluating major cardiovascular outcomes during follow-up. Among the overall cohort, 67.2% remained on semaglutide 1 mg, 29.2% escalated to semaglutide 2 mg and 3.6% switched to tirzepatide within 365 days of the index date. By 720 days, 36.9% had escalated to semaglutide 2 mg and 5.7% had switched to tirzepatide, reflecting continued treatment adjustment over time. The cardiovascular analysis included 185,705 adults who escalated to semaglutide 2 mg and 23,104 adults who switched to tirzepatide. The primary outcome was MACE, comprising all-cause death, myocardial infarction and stroke. Novo Nordisk reported an adjusted hazard ratio of 1.06 (95% CI 1.04–1.08; P=0.005) for the comparison, corresponding to the reported 6% lower associated risk with semaglutide dose escalation. A subset analysis involving patients with more than one HbA1c and/or weight measurement produced consistent findings, with an adjusted hazard ratio of 1.07 (95% CI 1.01–1.13; P<0.035).
Findings Add Cardiovascular Evidence for Semaglutide
The results provide additional information about cardiovascular outcomes associated with treatment intensification in adults with type 2 diabetes who are already receiving semaglutide. Novo Nordisk said the findings may provide healthcare professionals with additional real-world information when considering whether to increase the semaglutide dose or switch patients to another GLP-1-based treatment strategy. The analysis builds on an earlier COMPETE SWITCH assessment that examined HbA1c and weight outcomes, adding cardiovascular events as another outcome of interest. The study also provides insight into how tirzepatide was used after switching. Patients initially received tirzepatide at either 2.5 mg or 5 mg, with clinicians able to titrate treatment during follow-up. Approximately 31% of patients who switched to tirzepatide reached a dose of 10 mg or higher during the observation period. These treatment patterns illustrate the dynamic nature of diabetes management, where medication doses and therapies may be adjusted over time according to individual treatment needs and clinical response.
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Real-World Evidence Has Important Limitations
Although the findings provide a large-scale assessment of cardiovascular outcomes, the study was a retrospective observational analysis, rather than a randomized controlled clinical trial. Novo Nordisk noted that real-world analyses can be affected by residual or unmeasured confounding, meaning differences between treatment groups may influence observed associations. Claims-based datasets may also exclude certain patients with intermittent insurance coverage or underserved populations, potentially limiting how broadly the results can be generalized. Importantly, the analysis demonstrates an association rather than establishing a causal treatment effect. Novo Nordisk also stated that safety outcomes were not assessed in this particular analysis. The findings therefore focus specifically on cardiovascular outcomes associated with the treatment strategies studied. The company continues to evaluate semaglutide across diabetes and cardiometabolic disease programs, while real-world evidence such as the COMPETE SWITCH analysis adds information on how treatment strategies perform in routine clinical practice.
The latest findings contribute to the growing body of evidence surrounding GLP-1 receptor agonist treatment and cardiovascular outcomes in type 2 diabetes. By analyzing data from more than 636,000 adults, the COMPETE SWITCH study provides a substantial real-world dataset for examining what happens when patients receiving semaglutide 1 mg either increase their dose or change therapies. Further research, including prospective and randomized studies where appropriate, will remain important for determining how different treatment strategies affect cardiovascular and metabolic outcomes.
Source: Novo Nordisk press release
