Participants achieved an average weight loss of 20.2% with tirzepatide vs. 13.7% with semaglutide
In key secondary endpoints, tirzepatide was superior to semaglutide across all weight reduction targets and waist circumference reduction
Dubai, United Arab Emirates, May 12, 2025 — A clinical study has presented detailed findings from SURMOUNT-5, a phase 3b open-label clinical trial, evaluating the safety and efficacy of tirzepatide, a dual GIP and GLP-1 receptor agonist, compared to semaglutide, a mono GLP-1 receptor agonist, in adults living with obesity, or overweight with at least one weight-related medical problem and without diabetes. At 72 weeks, tirzepatide met the primary endpoint and all five key secondary endpoints, demonstrating superiority compared to semaglutide 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.
For the primary endpoint, participants treated with tirzepatide achieved an average weight reduction of 20.2% compared to 13.7% with semaglutide at 72 weeks using 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).2
In key secondary endpoints, 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 Louis J. Aronne, MD, FACP, DABOM, director of the Comprehensive Weight Control Center and the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine, obesity expert at New York-Presbyterian/Weill Cornell Medical Center, and 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.”
Primary and Key Secondary Endpoints:
| Tirzepatide | Semaglutide | |
| Primary Endpoint | ||
| Avg % weight loss | -20.2% | -13.7% |
| Key Secondary Endpoints | ||
| Achieved ≥10% weight loss | 81.6% | 60.5% |
| Achieved ≥15% weight loss | 64.6% | 40.1% |
| Achieved ≥20% weight loss | 48.4% | 27.3% |
| Achieved ≥25% weight loss | 31.6% | 16.1% |
| Waist circumference reduction | -18.4 cm | -13.0 cm |
“In the SURMOUNT-5 trial, tirzepatide demonstrated a significantly higher magnitude of weight reduction compared to semaglutide across all comparisons,” said Leonard Glass, MD, FACE, senior vice president, global medical affairs, Lilly. “These data confirm tirzepatide as a leading treatment option for people living with obesity and equip healthcare providers with critical insights to make well-informed treatment decisions as part of a comprehensive obesity care plan.”
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.
About SURMOUNT-5
SURMOUNT-5 (NCT05822830) was a 72-week, multi-center, randomized, 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, dyslipidemia, obstructive sleep apnea (OSA) or cardiovascular disease, who did not have diabetes. Participants in both treatment groups received counseling on a reduced-calorie diet and increased physical activity. The trial randomized 751 participants across the U.S. 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’s.
About tirzepatide
Tirzepatide is a once-weekly dual GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist. Tirzepatide is a single molecule that activates the body’s receptors for GIP and GLP-1, which are natural incretin hormones. Both GIP and GLP-1 receptors are found in areas of the human brain important for appetite regulation. Tirzepatide decreases calorie intake, and the effects are likely mediated by affecting appetite. Studies of tirzepatide in chronic kidney disease (CKD) and in morbidity/mortality in obesity (MMO) are ongoing.
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We’ve been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world’s most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer’s disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we’re motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY
