Journal-based CME Course: Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity – The SURMOUNT-4 Randomized Clinical Trial

Activity ID

13282

Expires

December 11, 2026

Format Type

Journal-based

CME Credit

1

Fee

30

CME Provider: JAMA

Description of CME Course

Importance  The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown.

Objective  To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction.

Design, Setting, and Participants  This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes.

Interventions  Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks.

Main Outcomes and Measures  The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period.

Results  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.

Conclusions and Relevance  In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction.

Trial Registration  ClinicalTrials.gov Identifier: NCT04660643

Disclaimers

1. This activity is accredited by the American Medical Association.
2. This activity is free to AMA members.

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