Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults with Obesity (SURMOUNT-4)

How does once-weekly subcutaneous tirzepatide affect maintenance of weight loss in individuals with obesity or overweight?

Methods: SURMOUNT-4 is a phase 3, double-blind, 88-week study that investigates the maximum tolerated dose (MTD) of tirzepatide (10 mg or 15 mg QW), compared with placebo, on the maintenance of weight loss for 52 weeks after an initial 36-week open-label tirzepatide lead-in treatment period. In the study, participants without T2DM and with obesity (BMI ≥30 kg/m^2) or overweight (BMI ≥27 kg/m^2) with at least 1 weight-related comorbid condition were enrolled. The efficacy estimand was used to assess efficacy which represented the average treatment effect, prior to treatment discontinuation.

Results: 803 participants enrolled in the lead-in period and 670 were randomized to continue tirzepatide MTD (N=335) or switch to placebo (N=335). For randomized participants, the mean weight loss was 20.9% following 36-week open-label treatment. SURMOUNT-4 met the primary endpoint. From week 36 to week 88, those taking tirzepatide had an additional weight change of -6.7%, while those taking placebo had a mean weight regain of 14.8%. The percentage of participants at 88 weeks who maintained ≥80% of the weight loss during the lead-in period was 93.4% with tirzepatide and 13.5% with placebo. In addition, participants who remained on tirzepatide achieved a total of 26.0% mean weight loss over the 88-week period. The most frequent adverse events with tirzepatide were gastrointestinal disorders, generally being mild to moderate in severity.

Conclusion: In this 88-week trial in participants with obesity or overweight, withdrawing tirzepatide after 36 weeks treatment led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction.

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Interessenkonflikt

Louis J. Aronne reported receiving grants from Allurion, Altimmune, AstraZeneca, Eli Lilly and Company, Gelesis, Janssen Pharmaceuticals, Novo Nordisk, and Versanis; consulting fees from Altimmune, Amgen, Eisai, Eli Lilly and Company, Gelesis, Jamieson Wellness, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Novo Nordisk, Optum, Pfizer, and Senda Biosciences; speaker fees honoraria from Cardiometabolic Health Congress, Harvard Obesity CME Course, and Obesity Medicine Association; a patent with Intellihealth; participating on scientific advisory boards for Altimmune, Amgen, Boehringer Ingelheim, Eisai, Eli Lilly and Company, ERX Pharmaceuticals, Gelesis, Jamieson Wellness, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Novo Nordisk, Pfizer, Senda Biosciences, and Versanis; serving as the chair emeritus on the American Board of Obesity Medicine, and on the board of directors for ERX Pharmaceuticals, Intellihealth, Jamieson Wellness, and MYOS Corp; and being a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, and Jamieson Wellness. Naveed Sattar reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; and grant support paid to his university from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics. Deborah B. Horn reported serving as a consultant/scientific advisor to Eli Lilly and Company, Gelesis, and Novo Nordisk; receiving speaker honoraria from Novo Nordisk; and research funding paid to her university from Eli Lilly and Company and Novo Nordisk. Harold E. Bays research site institution has received research grants from 89Bio, Alon Medtech/Epitomee, Altimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Fractyl, Kallyope, Novartis, NovoNordisk, Pfizer, Shionogi, Viking, and Vivus; Dr Bays reported serving as a consultant/advisor for 89Bio, Altimmune, Amgen, Boehringer Ingelheim, and Eli Lilly and Company. Sean Wharton reported receiving research funding, advisory/consulting fees, and/or other support from Bausch Health Canada Inc., Boehringer Ingelheim, CIHR, Eli Lilly and Company, BioHaven Pharmaceuticals, and Novo Nordisk. Wen-Yuan Lin reported no conflicts of interest. Nadia Nazir Ahmad, Shuyu Zhang, Ran Liao, Mathijs C. Bunck, Irina Jouravskaya, Madhumita A. Murphy are full-time employees of and shareholder in Eli Lilly and Company. No other disclosures were reported.

Publikationsverlauf

Artikel online veröffentlicht:
18. April 2024