Obesity is a serious chronic, progressive, and relapsing disease.1 Lifestyle interventions are a cornerstone of obesity management; however, sustaining weight reduction achieved through lifestyle-based caloric restriction is challenging.

Therefore, current guidelines recommend adjunctive antiobesity medications to promote weight reduction, facilitate weight maintenance, and improve health outcomes in people with obesity.2-4 Randomized withdrawal studies of antiobesity medications to date have consistently demonstrated clinically significant body weight regain with cessation of therapy.5,6 There is also evidence that antiobesity medications, including long-acting glucagon-like peptide-1 (GLP-1) receptor agonists, naltrexone/bupropion, phentermine/topiramate, and orlistat, may help maintenance of achieved weight reduction.5,7-12

Tirzepatide is a single molecule that combines glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonism13 resulting in synergistic effects on appetite, food intake, and metabolic function.14-16 Tirzepatide is approved in many countries, including the US, EU, and Japan, as a once-weekly subcutaneous injectable for type 2 diabetes and for the treatment of obesity in the US and UK.16-18 In a placebo-controlled trial of participants with obesity or overweight without diabetes, tirzepatide led to mean reductions in body weight up to 20.9% after 72 weeks of treatment.17,18

The aim of the SURMOUNT-4 trial was to investigate the effect of continued treatment with the maximum tolerated dose (ie, 10 or 15 mg) of once-weekly tirzepatide, compared with placebo, on the maintenance of weight reduction following an initial open-label lead-in treatment period in participants with obesity or overweight

articipants (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.

Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024;331(1):38–48. doi:10.1001/jama.2023.24945