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Randomized Controlled Trial
. 2020 Jun;28(6):1050-1061.
doi: 10.1002/oby.22794.

Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5

Robert F Kushner  1 , Salvatore Calanna  2 , Melanie Davies  3   4   5 , Dror Dicker  6   7 , W Timothy Garvey  8   9 , Bryan Goldman  2 , Ildiko Lingvay  10   11 , Mette Thomsen  2 , Thomas A Wadden  12 , Sean Wharton  13 , John P H Wilding  14 , Domenica Rubino  15
Affiliations
Randomized Controlled Trial

Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5

Robert F Kushner et al. Obesity (Silver Spring). 2020 Jun.

Abstract

Objective: The obesity epidemic is a public health concern, warranting further research into pharmacological treatments for weight management (WM) as an adjunct to lifestyle interventions. The Semaglutide Treatment Effect in People with obesity (STEP) program aims to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with obesity or overweight.

Methods: Across five phase 3 trials (NCT03548935, WM; NCT03552757, WM in type 2 diabetes; NCT03611582, WM with intensive behavioral therapy; NCT03548987, sustained WM; and NCT03693430, long-term WM), ~5,000 participants are being randomly assigned to receive semaglutide 2.4 mg once weekly subcutaneously versus placebo. Results will be available in 2020/2021. For all trials, the primary end point is change from baseline to end of treatment in body weight.

Results: Participants have a mean age of 46.2 to 55.3 years, are mostly female (mean: 74.1%-81.0%), and have a mean BMI of 35.7 to 38.5 kg/m2 and a mean waist circumference of 113.0 to 115.7 cm.

Conclusions: The STEP program evaluates the efficacy and safety of semaglutide 2.4 mg subcutaneously once weekly in a broad population. The trials will provide insights on WM in people with obesity with and without type 2 diabetes and on long-term follow-up.

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Conflict of interest statement

RFK has served on advisory boards for Novo Nordisk, received grant support during the conduct of these trials, and received fees for participating in educational films from Novo Nordisk. SC is an employee of and holds stock in Novo Nordisk. MD has received grant support from Novo Nordisk, Sanofi, Eli Lilly, Boehringer Ingelheim, and Janssen; has served on advisory boards and received consulting and speaker fees from AstraZeneca and Janssen; and has served on advisory boards for Servier and received speaker fees from Mitsubishi Tanabe Pharma Corporation and Takeda. DD has received grant support from Novo Nordisk and Boehringer Ingelheim and has served on advisory boards for and received consulting and speaker fees from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Teva, and Sanofi. WTG has served on advisory boards for Novo Nordisk, Sanofi, BOYDSense, Amgen, Gilead, and Boehringer Ingelheim and has received support for institutionally sponsored research from Sanofi, Pfizer, and Novo Nordisk. BG is an employee of and holds stock in Novo Nordisk. IL has received grant support from Novo Nordisk, Novartis, Pfizer, Merck, Mylan, and GI Dynamics; grant support for institutionally sponsored research from Novo Nordisk; and consulting fees from Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Sanofi, MannKind, Valeritas, Intarcia, and Janssen. MT is an employee of and holds stock in Novo Nordisk. TAW has served on advisory boards for Novo Nordisk and Weight Watchers and has received grant support, on behalf of the University of Pennsylvania, from Novo Nordisk. SW has received grant support and honoraria from and served on advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen and received nonfinancial support during the conduct of these trials. JPHW has received grant support from AstraZeneca, Novo Nordisk, and Takeda; has received personal fees from Boehringer Ingelheim, Napp, Novo Nordisk, Eli Lilly, Mundipharma, Sanofi, Janssen, and Takeda; and has served as a consultant for Astellas, AstraZeneca, Boehringer Ingelheim, Napp, Novo Nordisk, Eli Lilly, Mundipharma, Rhythm Pharmaceuticals, Sanofi, Janssen, and Wilmington Healthcare. DR has served on advisory boards for Arena, Eisai, Zafgen, and Novo Nordisk; has served as a clinical trials investigator for Bristol‐Myers Squibb, Merck, Nutrisource, Arena, Eisai, Vivus, Orexigen, Sanofi, AstraZenca, Novo Nordisk, and Weight Watchers; and has participated on a speaker’s bureau for Novo Nordisk and received grant support from Obeseinov SARL.

Figures

Figure 1
Figure 1
Weight management trial design (Semaglutide Treatment Effect in People with obesity 1). This is a 68‐week, randomized, double‐blind, placebo‐controlled, two‐armed, parallel‐group, multicenter, multinational clinical trial, with 7 weeks of follow‐up without treatment for safety assessments, comparing semaglutide 2.4 mg (subcutaneously, once weekly) with placebo, as an adjunct to lifestyle intervention, in people with obesity or overweight.
Figure 2
Figure 2
Weight management in type 2 diabetes (T2D) trial design (Semaglutide Treatment Effect in People with obesity 2). This is a 68‐week, randomized, double‐blind, double‐dummy, placebo‐controlled, three‐armed, multicenter, multinational clinical trial, with 7 weeks of follow‐up without treatment for safety assessments, comparing semaglutide 2.4 mg (subcutaneously, once weekly) with placebo, as an adjunct to lifestyle intervention, in people with obesity or overweight and T2D. *Randomization was stratified according to background diabetes treatment; diet and physical activity only or treatment with single‐compound metformin or sodium‐glucose cotransporter 2 inhibitor (SGLT2i) and single‐compound agents for diabetes (sulphonylurea [SU] or glitazone) or combination treatment with up to three agents for diabetes (metformin, SU, SGLT2i, or glitazone).
Figure 3
Figure 3
Weight management with intensive behavioral therapy trial design, only conducted in the United States (Semaglutide Treatment Effect in People with obesity 3). This is a 68‐week, randomized, double‐blind, placebo‐controlled, two‐armed, parallel‐group, multicenter clinical trial, with 7 weeks of follow‐up without treatment for safety assessments, comparing semaglutide 2.4 mg (subcutaneously, once weekly) with placebo, as an adjunct to intensive behavioral therapy and low‐calorie diet (LCD), in people with obesity or overweight.
Figure 4
Figure 4
Sustained weight management trial design (Semaglutide Treatment Effect in People with obesity 4). This is a 68‐week, randomized, double‐blind, placebo‐controlled, two‐armed, multicenter, multinational withdrawal clinical trial, with 7 weeks of follow‐up without treatment for safety assessments, comparing semaglutide 2.4 mg (subcutaneously, once weekly) with placebo, as an adjunct to lifestyle intervention, in people with obesity or overweight. *During the 20‐week run‐in period, participants start a dose escalation (visit 2 [week 0]) with semaglutide 2.4 mg (subcutaneously, once weekly) as an adjunct to a reduced‐calorie diet and increased physical activity for 20 weeks. The run‐in period includes 4 weeks at the target dose (semaglutide subcutaneously, 2.4 mg once weekly).
Figure 5
Figure 5
Long‐term weight management trial design (Semaglutide Treatment Effect in People with obesity 5). This is a 104‐week, randomized, double‐blind, placebo‐controlled, two‐armed, parallel‐group, multicenter, multinational clinical trial, with 7 weeks of follow‐up without treatment for safety assessments, comparing semaglutide 2.4 mg (subcutaneously, once weekly) with placebo, as an adjunct to lifestyle intervention in people with obesity or overweight.
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