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Clinical Trial
. 2023 Jan;31(1):96-110.
doi: 10.1002/oby.23612. Epub 2022 Dec 7.

Tirzepatide for the treatment of obesity: Rationale and design of the SURMOUNT clinical development program

Carel W le Roux  1 , Shuyu Zhang  2 , Louis J Aronne  3 , Robert F Kushner  4 , Ariana M Chao  5 , Sriram Machineni  6 , Julia Dunn  2 , Farai B Chigutsa  2 , Nadia N Ahmad  2 , Mathijs C Bunck  2
Affiliations
Clinical Trial

Tirzepatide for the treatment of obesity: Rationale and design of the SURMOUNT clinical development program

Carel W le Roux et al. Obesity (Silver Spring). 2023 Jan.

Abstract

Objective: Obesity is a growing global concern compounded by limited availability of effective treatment options. The SURMOUNT development program aims to evaluate the efficacy and safety of tirzepatide as an adjunct to lifestyle intervention compared with placebo on chronic weight management in adults with BMI ≥ 27 kg/m2 with or without type 2 diabetes.

Methods: The SURMOUNT program includes four global phase 3 trials NCT04184622 (SURMOUNT-1), NCT04657003 (SURMOUNT-2), NCT04657016 (SURMOUNT-3), and NCT04660643 (SURMOUNT-4). Participants are randomized to once-weekly subcutaneous tirzepatide versus placebo in a double-blind manner. The primary end point in all trials is the percentage change in body weight from randomization to end of treatment. Results for the primary end point for SURMOUNT-1 were published recently and results for the other trials are expected in 2023.

Results: Across trials, participants have a mean age of 44.9 to 54.2 years, are mostly female (50.7% to 69.7%), and have a mean BMI of 36.1 to 38.9.

Conclusions: The extensive assessment of once-weekly tirzepatide in the global SURMOUNT program will detail the clinical effects of this first-in-class glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist in chronic weight management.

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Conflict of interest statement

Carel W. le Roux serves on advisory boards of Novo Nordisk A/S, Herbalife, GI Dynamics, Eli Lilly and Company, Johnson & Johnson, Glia, and Boehringer Ingelheim. Carel W. le Roux was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. Louis J. Aronne reports receiving grants from Allurion, Altimmune, Aspire Bariatrics, AstraZeneca, Eisai, Eli Lilly and Company, Gelesis, Janssen Pharmaceuticals, and Novo Nordisk A/S, consulting fees from Altimmune, Eisai, Eli Lilly and Company, Gelesis, Jamieson Wellness, Janssen Pharmaceuticals, Novo Nordisk A/S, Pfizer, Optum, 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, Eisai, Eli Lilly and Company, ERX Pharmaceuticals, Gelesis, Jamieson Wellness, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Novo Nordisk A/S, Pfizer, Optum, and Senda Biosciences, serves as the chair emeritus on the American Board of Obesity Medicine, and on the board of directors for ERX Pharmacueticals, Intellihealth, Jamieson Wellness, and MYOS Corp, and is a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, Jamieson Wellness and MYOS Corp. Sriram Machineni receives research funding from Eli Lilly and Company, Novo Nordisk, Rhythm Pharmaceuticals, and Boeringher Ingelheim and serves as a aconsultant for Novo Nordisk and Rhythm Pharmaceuticals and on the Scientific Advisory Board for Eli Lilly and Company. Shuyu Zhang, Julia Dunn, Farai B. Chigutsa, Nadia N. Ahmad, and Mathijs C. Bunck are employees and shareholders of Eli Lilly and Company. Robert F. Kushner reports receiving advisory board fees from Novo Nordisk A/S and WW International, Inc. Ariana M. Chao reports grant support from Eli Lilly and Company and WW International, Inc. No other potential conflicts of interest were reported.

Figures

FIGURE 1
FIGURE 1
SURMOUNT‐1 study design. This is a phase 3, multicenter, randomized, placebo‐controlled, double‐blind clinical trial investigating the safety and efficacy of 5, 10, and 15 mg tirzepatide administered QW subcutaneously compared with placebo for weight management as an adjunct to a reduced‐calorie diet and increased physical activity in participants with BMI ≥ 30 or ≥27 with obesity‐related complications (excluding type 2 diabetes).*Participants who had prediabetes at randomization but discontinued the study during the 72‐week treatment period were included in the 4‐week safety follow‐up. QW, once weekly
FIGURE 2
FIGURE 2
SURMOUNT‐2 study design. This is a phase 3, multicenter, randomized, placebo‐controlled, double‐blind, 72‐week clinical trial investigating the safety and efficacy of tirzepatide 10 and 15 mg administered QW subcutaneously compared with placebo on weight management, as an adjunct to a reduced‐calorie diet and increased physical activity, in participants with type 2 diabetes and BMI ≥ 27. QW, once weekly
FIGURE 3
FIGURE 3
SURMOUNT‐3 study design. This is a phase 3, multicenter, randomized, placebo‐controlled, double‐blind, 84‐week clinical trial investigating the safety and efficacy of the MTD of tirzepatide (10 or 15 mg), administered subcutaneously QW, compared with placebo, on body weight management in participants who have BMI ≥ 30 or ≥27 with obesity‐related complications (excluding type 2 diabetes) and achieve ≥5.0% weight reduction after a 12‐week lead‐in period on an intensive lifestyle modification program. MTD, maximum tolerated dose; QW, once weekly
FIGURE 4
FIGURE 4
SURMOUNT‐4 study design. This is a phase 3, multicenter, randomized, placebo‐controlled, double‐blind, 88‐week clinical trial investigating the safety and efficacy of the MTD of tirzepatide (10 or 15 mg), administered subcutaneously QW, compared with placebo, on the maintenance of weight reduction after an initial 36‐week open‐label tirzepatide lead‐in treatment period in participants with BMI ≥ 30 or ≥27 with obesity‐related complications (excluding type 2 diabetes). MTD, maximum tolerated dose; QW, once weekly
FIGURE 5
FIGURE 5
Schematic presentation of trials in the global obesity program. CKD, chronic kidney disease; CVD, cardiovascular disease; NAFLD, nonalcoholic fatty liver disease; T2D, type 2 diabetes
See this image and copyright information in PMC

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