In a head-to-head randomized trial of adult patients with obesity, tirzepatide achieved a 20.2% mean reduction in body weight compared with 13.7% with semaglutide at 72 weeks, according to results from the SURMOUNT-5 trial.
In the 72-week, phase IIIb, multicenter, open-label, randomized trial, researchers evaluated the safety and efficacy of tirzepatide versus semaglutide in 751 adult patients with obesity but without type 2 diabetes.
The participants were randomly assigned 1:1 to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or semaglutide (1.7 mg or 2.4 mg) as a once-weekly subcutaneous injection. Randomization was stratified by baseline body mass index (BMI), sex, and prediabetes status.
Tirzepatide was superior to semaglutide with respect to reduction in body weight and waist circumference at week 72, wrote lead study author Louis J. Aronne, MD, of Weill Cornell Medicine, and colleagues.
The participants receiving tirzepatide were more likely to achieve key weight-reduction targets. The percentage of participants achieving reductions in body weight of at least 10%, 15%, 20%, and 25% was higher in the tirzepatide group compared with the semaglutide group: 81.6% versus 60.5%, 64.6% versus 40.1%, 48.4% versus 27.3%, and 31.6% versus 16.1%, respectively. Additionally, 19.7% of the participants receiving tirzepatide achieved a weight reduction of 30% or more compared with 6.9% among those in the semaglutide group.
The least-squares mean change in waist circumference was −18.4 cm with tirzepatide vs −13 cm with semaglutide. Greater weight reductions were associated with greater improvements in cardiometabolic risk factors, including reductions in systolic and diastolic blood pressure, glycated hemoglobin, fasting glucose, and lipid levels.
The safety profiles of both medications were consistent with previous trials. Gastrointestinal adverse events, including nausea, diarrhea, vomiting, and constipation, were the most common and generally occurred during dose escalation. These events were mild to moderate in severity among most participants. Discontinuation as a result of gastrointestinal adverse events occurred more frequently among the participants who received semaglutide (5.6%) compared with those who received tirzepatide (2.7%). Injection-site reactions were also more frequent with tirzepatide (8.6%) than with semaglutide (0.3%).
The trial population had a mean age of 44.7 years, mean body weight of 113 kg, and mean BMI of 39.4. Approximately 64.7% of the participants were female. Racial and ethnic diversity was representative of the broader population of adult patients with obesity: 19.2% identified as Black and 26.1% identified as Hispanic or Latino. Notably, weight reduction was approximately 6% greater among female participants compared with among male participants in both treatment groups.
“Tirzepatide pharmacologically activates two metabolic receptors, GIP and GLP-1, which have both overlapping and nonoverlapping expression and function,” the study authors explained. “This dual-agonism activity of tirzepatide may contribute to the greater weight reduction observed with tirzepatide than with semaglutide, a monoagonist used in the current trial."
The SURMOUNT-5 trial was funded by Eli Lilly, the manufacturer of tirzepatide.
Disclosures can be found in the published study.