Diabetes, obesity & metabolismOct 18, 2022

Semaglutide as a treatment for overweight and obesity

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Mar 31, 2026

Abstract

Semaglutide 2.4 mg is associated with mean weight losses of 14.9%-17.4% among individuals with overweight or obesity without type 2 diabetes over 68 weeks.

69%-79% of participants achieved at least 10% weight loss with semaglutide 2.4 mg compared to 12%-27% with placebo.
51%-64% of participants achieved at least 15% weight loss with semaglutide 2.4 mg, while 5%-13% achieved this with placebo.
In individuals with overweight or obesity and type 2 diabetes, mean weight loss was -9.6% with semaglutide 2.4 mg versus -3.4% with placebo over 68 weeks.
Improvements in cardiometabolic risk factors, such as high blood pressure and atherogenic lipids, were observed with semaglutide 2.4 mg.
The safety profile of semaglutide 2.4 mg was consistent across trials, primarily involving gastrointestinal adverse events.

Simplified

Obesity is a chronic, relapsing disease associated with multiple complications and a substantial morbidity, mortality and health care burden. Pharmacological treatments for obesity provide a valuable adjunct to lifestyle intervention, which often achieves only limited weight loss that is difficult to maintain. The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial programme is evaluating once-weekly subcutaneous semaglutide 2.4 mg (a glucagon-like peptide-1 analogue) in people with overweight or obesity. Across STEP 1, 3, 4 and 8, semaglutide 2.4 mg was associated with mean weight losses of 14.9%-17.4% in individuals with overweight or obesity without type 2 diabetes from baseline to week 68; 69%-79% of participants achieved ≥10% weight loss with semaglutide 2.4 mg (vs. 12%-27% with placebo) and 51%-64% achieved ≥15% weight loss (vs. 5%-13% with placebo). In STEP 5, mean weight loss was -15.2% with semaglutide 2.4 mg versus -2.6% with placebo from baseline to week 104. In STEP 2 (individuals with overweight or obesity, and type 2 diabetes), mean weight loss was -9.6% with semaglutide 2.4 mg versus -3.4% with placebo from baseline to week 68. Improvements in cardiometabolic risk factors, including high blood pressure, atherogenic lipids and benefits on physical function and quality of life were seen with semaglutide 2.4 mg. The safety profile of semaglutide 2.4 mg was consistent across trials, primarily gastrointestinal adverse events. The magnitude of weight loss reported in the STEP trials offers the potential for clinically relevant improvement for individuals with obesity-related diseases.

Key numbers

14.9%-17.4%

Mean Weight Loss

Weight loss percentage from baseline to week 68 in participants without diabetes.

69%-79%

Participants Achieving ≥10% Weight Loss

Proportion of participants achieving this milestone with semaglutide 2.4 mg vs. placebo.

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Funding

Competing interests

NCB declared no conflict of interest. MJD is a consultant, advisory board member and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi‐Aventis; advisory board member and speaker for AstraZeneca; advisory board member for Gilead Sciences Ltd, Janssen, Lexicon, Pfizer and Servier; speaker for Mitsubishi Tanabe Pharma Corporation, Napp Pharmaceuticals and Takeda Pharmaceuticals International Inc.; received grants to support investigator and investigator‐initiated trials from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi‐Aventis. MJD is co‐funded by the NIHR Leicester Biomedical Research Centre. IL obtained research funding, advisory/consulting fees, and/or other support from AstraZeneca, Bayer, Boehringer Ingelheim, GI Dynamics, Intarcia, Intercept, Janssen, Eli Lilly, Mannkind, Merck, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, TARGETPharma, Valeritas and Zealand Pharma. FKK served on scientific advisory panels and/or been part of speaker bureaus for, served as a consultant to and/or received research support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, Lupin, MedImmune, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Pharmacosmos, Sanofi, ShouTi, Zealand Pharma and Zucara; minority shareholder in Antag Therapeutics.

PubMed

Semaglutide as a treatment for overweight and obesity

Abstract

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Funding

Competing interests

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