Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.
Level 2 - randomized trial
Phase 3 randomized controlled withdrawal trial
PubMed 38078870 · doi:10.1001/jama.2023.24945
What was done
This phase 3 randomized withdrawal trial conducted at 70 sites across 4 countries evaluated weight maintenance in adults with obesity (BMI >= 30) or overweight (BMI >= 27 with weight-related complications, excluding diabetes). Following a 36-week open-label lead-in with once-weekly subcutaneous tirzepatide (10 or 15 mg maximum tolerated dose; n=783), 670 participants were randomized 1:1 to continue tirzepatide (n=335) or switch to placebo (n=335) double-blind for 52 weeks, combined with diet and physical activity counseling. The primary endpoint was mean percent weight change from week 36 (randomization) to week 88.
What was found
During the 36-week lead-in, participants experienced a mean weight reduction of 20.9%. From week 36 to week 88, the mean percent weight change was -5.5% with continued tirzepatide versus +14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). At week 88, 89.5% (300/335) of participants receiving tirzepatide maintained at least 80% of lead-in weight loss compared with 16.6% receiving placebo (P < .001). Total mean weight reduction from week 0 to 88 was 25.3% for tirzepatide versus 9.9% for placebo. Gastrointestinal adverse events were mostly mild to moderate and occurred more frequently with tirzepatide than placebo.
Why it matters
This trial demonstrates that tirzepatide provides sustained and augmented weight loss with ongoing treatment, but drug discontinuation results in rapid weight regain, indicating obesity management with tirzepatide requires chronic therapy.
Limits
Adults with diabetes were excluded. The study design enriched for responders and tolerant individuals by randomizing only the 670 participants who completed the 36-week lead-in (113 of 783 initial enrollees did not undergo randomization). Long-term outcomes beyond 88 weeks were not evaluated.