Tirzepatide Bests Semaglutide for Weight Loss: SURMOUNT-5 Topline Results

In a head-to-head tussle between two obesity drugs, tirzepatide came out on top of semaglutide for weight loss, according to topline results from the SURMOUNT-5 trial released by Eli Lilly on Wednesday.

Tirzepatide (Zepbound; Eli Lilly) is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist, while semaglutide (Wegovy; Novo Nordisk) is a GLP-1 receptor agonist.

In SURMOUNT-5, a randomized trial of 751 patients with obesity or overweight and at least one weight-related comorbidity, such as hypertension, dyslipidemia, or cardiovascular disease, use of tirzepatide resulted in 47% greater weight loss compared with semaglutide over 72 weeks of treatment. On average, tirzepatide cut body weight from baseline by 20.2% compared with 13.7% in those taking semaglutide.

Additionally, more than 31% of patients taking tirzepatide achieved a 25% reduction in body weight, one of the study’s secondary endpoints, compared with 16.1% in those taking semaglutide. The most commonly reported side effects with both drugs were mild-to-moderate gastrointestinal issues, Eli Lilly said in a press release.

Tirzepatide is currently approved by the US Food and Drug Administration for chronic weight management in adults with obesity or overweight and a weight-related condition. Semaglutide, too, is approved for chronic weight management, but it also has an indication for the prevention of cardiovascular disease on the basis of the SELECT trial. Both drugs are approved, under different trade names (Mounjaro and Ozempic, respectively) for the treatment of type 2 diabetes.

Both tirzepatide, in SUMMIT, and semaglutide, in STEP-HFpEF, have been shown to be effective in patients with heart failure with preserved ejection (HFpEF). Additionally, Eli Lilly is currently running SURPASS-CVOT, a large-scale, cardiovascular outcomes study comparing two of its drugs, tirzepatide and dulaglutide (Trulicity), in patients with type 2 diabetes.

Full results of SURMOUNT-5 are expected to be published and presented at a major medical meeting in 2025, Eli Lilly said.