SURMOUNT-5: Tirzepatide shows superior weight loss over semaglutide

Seventy-two week outcomes from the SURMOUNT-5 clinical trial have shown that tirzepatide (Zepbound) met the primary endpoint and all five key secondary endpoints, demonstrating superiority, compared to semaglutide (Wegovy) across the trial.  The detailed results were presented at the 32nd European Congress on Obesity (ECO) and simultaneously published in The New England Journal of Medicine. 

SURMOUNT-5 was a 72-week, multi-centre, randomised, open-label, Phase 3b trial evaluating the efficacy and safety of tirzepatide compared with semaglutide in adults with obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidaemia, obstructive sleep apnoea (OSA) or cardiovascular disease, who did not have diabetes. Participants in both treatment groups received counselling on a reduced-calorie diet and increased physical activity.

The trial randomized 751 participants across the US and Puerto Rico in a 1:1 ratio to receive maximum tolerated dose of tirzepatide (10 mg or 15 mg) or semaglutide (1.7 mg or 2.4 mg). With tirzepatide, 89.3% received at least one dose of the 15 mg dose and with semaglutide 92.8% received at least one dose of the 2.4 mg dose. The primary objective of the study was to demonstrate tirzepatide’s superiority in percent change from baseline in body weight at 72 weeks compared to semaglutide.

For the primary endpoint (Table 1), participants treated with tirzepatide achieved an average weight reduction of 20.2% compared to 13.7% with semaglutide at 72 weeks using the treatment-regimen estimand,1 a 47% greater relative weight loss. Participants using tirzepatide lost an average of 50.3 lbs (22.8 kg) and participants on semaglutide lost an average of 33.1 lbs (15.0 kg).

Table 1

In key secondary endpoints (Table 1), tirzepatide was superior across all weight reduction targets with 64.6% of participants treated with tirzepatide achieving at least 15.0% weight loss compared to 40.1% on semaglutide. Additionally, participants treated with tirzepatide achieved a superior average waist circumference reduction of 7.2 in (18.4 cm), while those treated with semaglutide saw an average reduction of 5.1 in (13.0 cm).

"Thanks to the latest advancements in obesity management medications, more physicians and patients are witnessing significant weight reduction beyond what they have seen before," said Dr Louis J Aronne, director of the Comprehensive Weight Control Center and the Sanford I Weill Professor of Metabolic Research at Weill Cornell Medicine, an internist specialising in diabetes and obesity at New York-Presbyterian/Weill Cornell Medical Center, and principal investigator of SURMOUNT-5. "The SURMOUNT-5 head-to-head results demonstrated tirzepatide led to greater weight reduction compared to semaglutide, providing further evidence to support tirzepatide as an effective option for obesity management."

The safety profile of tirzepatide in SURMOUNT-5 was consistent with previous SURMOUNT trials. Adverse events reported during the trial were primarily gastrointestinal-related and were generally mild to moderate in severity. During the trial, 6.1% of participants taking tirzepatide discontinued treatment due to adverse events, compared to 8.0% of participants taking semaglutide. However, the study was not powered to compare the safety and tolerability of tirzepatide and the safety and tolerability of semaglutide.