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Review
. 2023 Jan;25(1):18-35.
doi: 10.1111/dom.14863. Epub 2022 Oct 18.

Semaglutide for the treatment of overweight and obesity: A review

Natasha Chidekel Bergmann  1 , Melanie J Davies  2   3 , Ildiko Lingvay  4 , Filip K Knop  5   6   7
Affiliations
Review

Semaglutide for the treatment of overweight and obesity: A review

Natasha Chidekel Bergmann et al. Diabetes Obes Metab. 2023 Jan.

Abstract

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.

Keywords: GLP-1 analogue; anti-obesity drug; obesity therapy; weight management.

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Conflict of interest statement

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.

Figures

FIGURE 1
FIGURE 1
Key considerations for using once‐weekly subcutaneous semaglutide 2.4 mg in clinical practice (approved in Canada, Europe, the UK and the USA)., , , Abbreviations: AE, adverse event; GI, gastrointestinal; GLP‐1RA, glucagon‐like peptide‐1 receptor agonist
FIGURE 2
FIGURE 2
Future landscape of obesity pharmacotherapy. Ongoing trials with semaglutide, and selected ongoing and completed trials with other investigational agents. Studies in closed boxes are completed, while those in open boxes are ongoing. Abbreviations: CVD, cardiovascular disease; CVOT, cardiovascular outcomes trial; HF, heart failure; LTE, long‐term extension; OA, osteoarthritis; T2D, type 2 diabetes
See this image and copyright information in PMC

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