Novo Nordisk: semaglutide 2 mg linked to lower MACE vs tirzepatide in COMPETE SWITCH CV analysis

Findings

In a retrospective real-world analysis presented at EASD 2026, adults on once-weekly semaglutide 1 mg who escalated to semaglutide 2 mg were associated with a statistically significant 6% lower risk of major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, stroke) compared with those who switched to tirzepatide up to 15 mg (Adjusted HR 1.06; 95% CI 1.04–1.08; P=0.005). A subset with multiple baseline HbA1c and/or weight measures showed consistent results (Adjusted HR 1.07; 95% CI 1.01–1.13; P<0.035).

Study design and exposure patterns

The COMPETE SWITCH analysis used Komodo Health claims with linked labs (January 2018–September 2025) and began from the first semaglutide 1 mg fill; the full analysis cohort comprised 636,525 adults. At index, 67.2% remained on semaglutide 1 mg; within 365 days 29.2% escalated to 2 mg and 3.6% switched to tirzepatide. By 720 days 36.9% had escalated and 5.7% had switched. Among switchers, ~31% reached ≥10 mg tirzepatide during follow-up. The cardiovascular component followed 185,705 escalators and 23,104 switchers using an intention-to-treat approach.

Limitations and safety

Authors note that retrospective claims analyses can show associations but not definitive causation and may suffer residual unmeasured confounding and limited generalizability. Safety outcomes were not assessed in this analysis. The report also restates that semaglutide carries a Boxed Warning for potential thyroid tumors including medullary thyroid carcinoma and lists common adverse effects such as nausea, vomiting, diarrhea, abdominal pain, and constipation.