The tirzepatide molecule is a 39 amino acid linear peptide conjugated to a C20 fatty acid moiety. Tirzepatide image from Lilly.
A phase 3b open-label randomized clinical trial (SURMOUNT-5) has shown that tirzepatide leads to greater weight reduction compared to semaglutide in adults with obesity or overweight conditions. The study from Eli Lilly demonstrated a mean weight loss of 20.2% with tirzepatide (Zepbound) versus 13.7% with semaglutide (Wegovy) over a 72-week period.
Last year, a pre-print reached similar conclusions, finding that tirzepatide users were significantly more likely to achieve meaningful weight loss than semaglutide recipients.
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). While the study’s design as an open-label trial warrants consideration when interpreting results, 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.
[Stock data from yfinance]
Performance metrics
- 20.2% mean weight loss with tirzepatide vs. 13.7% with semaglutide
- 50.3 lbs average weight loss with tirzepatide vs. 33.1 lbs with semaglutide
- 31.6% of tirzepatide group achieved ≥25% weight loss vs. 16.1% with semaglutide
- 72-week study duration
- 751 total participants
Technical details
The researchers documented that 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). In the end, 31.6% of tirzepatide recipients achieved ≥25% body weight reduction compared to 16.1% in the semaglutide group. The safety profile aligned with previous SURMOUNT trials, with gastrointestinal effects reported as the primary adverse events for both medications.
Longer-term studies are still 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.
In August 2024, Lilly announced long-term data from another trial in the same series — 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. The trial, which represents the longest completed study of the drug, revealed that participants achieved an average weight reduction of 22.9%, while the placebo group only lost 2.1%.
Filed Under: Metabolic disease/endicrinology
