In the SURMOUNT-4 trial, withdrawal of tirzepatide led to rapid weight regain among participants with obesity or overweight, researchers report. In those who continued the drug after a 36-week treatment period, weight loss was maintained and augmented over a 52-week continuation phase.
The phase 3 trial at 70 sites in 4 countries included adults with a body mass index of 30 or between 27 and 30 with a weight-related complication, excluding diabetes. Participants received once-weekly subcutaneous maximum tolerated doses (10 or 15 mg) of tirzepatide for 36 weeks in an open-label, lead-in phase. They were then randomized to continue tirzepatide or switch to placebo for 52 weeks.
Based on a primary endpoint of the mean percent change in weight from the randomization point at week 36 to the end of the trial at week 88, the study showed the following: “Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was −5.5% with tirzepatide vs 14.0% with placebo (difference, −19.4% [95% CI, −21.2% to −17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo.”