Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity
Authors: Aronne Louis J. , Sattar Naveed , Horn Deborah B. , Bays Harold E. , Wharton Sean , Lin Wen-Yuan , Ahmad Nadia N. , Zhang Shuyu , Liao Ran , Bunck Mathijs C. , Jouravskaya Irina , Murphy Madhumita A. ,   SURMOUNT-4 Investigators, Fretes José O , Coronel Maria J , Gutnisky Lucas L , Frechtel Gustavo D , Gelersztein Elizabeth , Aizenberg Diego , Maldonado Natacha , Pereira Márcio , Santos Queulla G , Calil Salim Camila , Canani Luis H , Halpern Bruno , Russo Luis AT , Bodart Joselita , Neto Danilo V , Augusto Gustavo , Leite Silmara , Yang Yi-Ching , Lin Wen-Yuan , Huang Chien-Ning , Huang Kuo-Chin , Fitz-Patrick David , Pau Cindy HT , Toth Phillip D , Freeman George H , Gardner Donald F , Wynne Alan G , Loy Juan , Horn Deborah B , Mehra Purvi K , Layle Stacey , Bergthold James H , de Souza Jose , Nadar Venkatesh K , Albizu Angulo Gustavo R , Cohen Kenneth R , Smith Timothy R , Aronne Louis J , Vaughn Michael , Alcantara-Gonzalez Altagracia A , Forman Seth B , Agaiby John M , Geller Steven A , Fraser Neil J , Jenders Robert A , Barbel-Johnson Kim M , Mayfield Ronald K , Vance Carl D , Prier Kevin T , Murray Alexander V , Lillestol Michael J , Denham Douglas S , Park Jean Y , Klein Eric J , Bays Harold E , Philis-Tsimikas Athena , Bressler Peter E , Reed John CH , Aslam Shamaila , Rosenstock Julio , Frias Juan P , Klaff Leslie J , Brazg Ronald , Gomez-Cuellar Martha , Connery Lisa , Van Joanna T , Selam Jean-Louis , Kim John , Blake Dwight , Gabriel John , Arora Samir , McCartney Michael J , Solano Royce K , Brodie Steven K , Nardandrea John P 
Published: December 2023

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 &amp;lt; .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 &amp;lt; .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