Novo, Lilly each claim an edge in GLP-1 dosing data

Clinical takeaway: Escalating semaglutide was linked to fewer cardiovascular events than switching to tirzepatide in adults with type 2 diabetes. Tirzepatide was associated with more weight loss than high-dose semaglutide, but the difference was not consistently statistically significant. 

Semaglutide and tirzepatide now compete for the same patients in diabetes and obesity care, and the choice between them comes up at more than one point. A patient who tolerates semaglutide but hasn't reached goals can move to a higher dose or switch to tirzepatide. A patient starting weight-loss treatment can be offered either drug from the outset. Each manufacturer has an argument for why its drug is the best place to land, and both offer new data to frame the conversation. 

Two new analyses take up similar questions from opposite sides. Novo starts with patients already on semaglutide and asks whether raising the dose does better than switching, judged by cardiovascular events. Lilly starts with tirzepatide and asks how it compares with high-dose semaglutide, judged by weight loss. Each extends the comparison into dose-level territory the head-to-head randomized trial that found tirzepatide outperformed lower doses of semaglutide didn't reach. 

Adults on semaglutide 1 mg who moved up to 2 mg had 6% lower risk of major adverse cardiovascular events, a composite of death from any cause, MI, and stroke, than those who switched to tirzepatide. An analysis limited to patients with more than one A1C or weight measurement at baseline pointed the same way. Only about 31% of patients who switched reached tirzepatide 10 mg or higher, so most were compared at lower tirzepatide doses. 

Tirzepatide 15 mg was associated with 4.5% more weight loss than semaglutide 7.2 mg at 72 weeks when every patient was counted whether or not they stayed on treatment, and 10 mg was associated with 3.2% more. When assessing weight loss only while patients were taking the drug, the differences shrank to 1.8% and 0.7%, and neither was statistically significant. Tirzepatide 15 mg was also associated with more than threefold the odds of losing at least 20% of body weight when every patient was counted and about fourfold the odds when only patients taking the drug were counted, though the confidence intervals were wide. The 10 mg tirzepatide dose did not reach statistical significance on the 20% threshold under either way of counting patients. Discontinuation because of adverse events was comparable with semaglutide 7.2 mg under both. 

The Novo analysis was a retrospective cohort study of US claims data from January 2018 through September 2025, comparing 185,705 adults who increased semaglutide dosage from 1 mg to 2 mg with 23,104 who switched to tirzepatide. Lilly's was an indirect comparison of two trials, SURMOUNT-1 of tirzepatide and STEP UP of semaglutide 7.2 mg, adjusted for age, sex, baseline weight, and A1C in adults with obesity but without type 2 diabetes. 

On weight loss, tirzepatide retains its edge, but the semaglutide answer has been to move to a higher dose. The contest is now about dose as much as drug, and at the higher dose each side is arguing from indirect evidence. 

On heart outcomes, the drugs have not been tested in a randomized head-to-head trial. Semaglutide's best evidence is placebo-controlled, including a 20% lower risk of major cardiovascular events in adults with overweight or obesity and established heart disease but no diabetes. Tirzepatide's best cardiovascular evidence compares it with dulaglutide, another GLP-1 drug, and it was noninferior but not superior in adults with type 2 diabetes. 

Both drugs now carry an FDA cardiovascular indication, Wegovy since March 2024 for adults with established heart disease and overweight or obesity, and Mounjaro since August 2026 for adults with type 2 diabetes at high cardiovascular risk. 

"For people living with obesity, the choice of treatment matters, and clinicians increasingly want evidence on how the available options compare," said John Wilding, DM, professor of medicine at the University of Liverpool. "Tirzepatide 10 mg and 15 mg and semaglutide 1.7 mg and 2.4 mg were compared directly in SURMOUNT-5, where tirzepatide helped people with obesity lose more weight. In the absence of a head-to-head trial comparing tirzepatide 15 mg against semaglutide 7.2 mg, this indirect comparison offers useful evidence for physicians as they make treatment decisions." 

Sources: Novo Nordisk. (2026 Sep 29) Novo's Ozempic 2 mg associated with lower risk of major adverse cardiovascular events in adults with type 2 diabetes compared to switching to Mounjaro, in real-world analysis at EASD; Eli Lilly and Company. (2026 Sep 29) Lilly's Zepbound was associated with more weight loss than Wegovy HD in a new indirect treatment comparison