A phase 3b open-label randomized clinical trial, SURMOUNT-5, has revealed that tirzepatide leads to significantly greater weight reduction compared to semaglutide in adults with obesity or overweight. The study, conducted by Eli Lilly, demonstrated a mean weight loss of 20.2% with tirzepatide (Zepbound) versus 13.7% with semaglutide (Wegovy) over a 72-week period, marking a 47% greater relative weight loss.
The SURMOUNT-5 trial enrolled 751 participants across the U.S. and Puerto Rico, employing a 1:1 randomization protocol comparing maximum tolerated doses of tirzepatide (10mg or 15mg) to semaglutide (1.7mg or 2.4mg). The trial supports the superiority of tirzepatide’s dual-action mechanism targeting both GIP and GLP-1 receptors, compared to semaglutide’s single GLP-1 receptor targeting approach.
Weight Loss Performance
Participants receiving tirzepatide achieved an average weight reduction of 50.3 lbs (22.8 kg), while those on semaglutide lost 33.1 lbs (15.0 kg). 31.6% of tirzepatide recipients achieved ≥25% body weight reduction compared to 16.1% in the semaglutide group. The safety profile was consistent with previous SURMOUNT trials, with gastrointestinal effects being the primary adverse events for both medications.
"Given the increased interest around obesity medications, we conducted this study to help health care providers and patients make informed decisions about treatment choice," said Leonard C. Glass, MD, FACE, senior vice president of global medical affairs at Lilly Cardiometabolic Health.
Long-Term Efficacy and Safety
Longer-term studies are needed to evaluate sustained efficacy and safety beyond 72 weeks. Ongoing research includes investigations into chronic kidney disease impacts and morbidity/mortality outcomes in obesity. Additional studies examining tirzepatide’s effects on obstructive sleep apnea and heart failure with preserved ejection fraction are under regulatory review.
Tirzepatide's Impact on Diabetes Prevention
In August 2024, Lilly announced long-term data from the SURMOUNT-1 trial, demonstrating tirzepatide’s impact on diabetes prevention. The three-year study of 1,032 adults showed that weekly injections of tirzepatide cut the risk of developing Type 2 diabetes by 94% in prediabetic adults who were overweight or obese, compared to placebo. Participants achieved an average weight reduction of 22.9%, while the placebo group only lost 2.1%.
