Physiology of Weight Regain after Weight Loss: Latest Insights

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Abstract

Purpose of Review

This review summarizes the most recent research on the physiology of weight regain. It describes developments in areas that are currently being addressed and that may indicate promising directions for future research.

Recent Findings

Weight regain occurs independent of the way prior weight loss is achieved, i.e. by lifestyle, surgery or pharmacotherapy. Recent novel findings regarding weight regain belong to four areas. First, the immune obesity memory of which besides persistent immune cells promoting weight regain cells have been found that reduce weight regain. Second, the gut microbiome where autologous transplantation can limit weight regain. Third, the composition of the weight loss with the percentage of lost fat-free mass being inverse to the amount of regained weight independent of the weight loss procedure. Fourth, appetite control where after weight loss altered hypothalamic activity promoting hunger and weight regain persists, possibly mediated by altered neurotensin responses. In all four areas more conclusive evidence for their role in weight regain still needs to be obtained.

Summary

Most studies on physiological mechanisms of weight regain are associative in nature and the number of intervention studies is very limited. To bring the field further, carefully designed intervention studies taking into account the dynamic character of weight loss and weight regain are needed.

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Most cited references 40

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Maintenance of Lost Weight and Long-Term Management of Obesity

Kevin D. Hall, Scott Kahan (2018)

Weight loss can be achieved through a variety of modalities, but long-term maintenance of lost weight is much more challenging. Obesity interventions typically result in early weight loss followed by a weight plateau and progressive regain. This review describes current understanding of the biological, behavioral, and environmental factors driving this near-ubiquitous body weight trajectory and the implications for long-term weight management. Treatment of obesity requires ongoing clinical attention and weight maintenance-specific counseling to support sustainable healthful behaviors and positive weight regulation.

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Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension

John Wilding, Rachel L Batterham, Melanie L Davies … (2022)

Abstract Aim To explore changes in body weight and cardiometabolic risk factors after treatment withdrawal in the STEP 1 trial extension. Materials and Methods STEP 1 (NCT03548935) randomized 1961 adults with a body mass index ≥ 30 kg/m2 (or ≥ 27 kg/m2 with ≥ 1 weight‐related co‐morbidity) without diabetes to 68 weeks of once‐weekly subcutaneous semaglutide 2.4 mg (including 16 weeks of dose escalation) or placebo, as an adjunct to lifestyle intervention. At week 68, treatments (including lifestyle intervention) were discontinued. An off‐treatment extension assessed for a further year a representative subset of participants who had completed 68 weeks of treatment. This subset comprised all eligible participants from any site in Canada, Germany and the UK, and sites in the United States and Japan with the highest main phase recruitment. All analyses in the extension were exploratory. Results Extension analyses included 327 participants. From week 0 to week 68, mean weight loss was 17.3% (SD: 9.3%) with semaglutide and 2.0% (SD: 6.1%) with placebo. Following treatment withdrawal, semaglutide and placebo participants regained 11.6 (SD: 7.7) and 1.9 (SD: 4.8) percentage points of lost weight, respectively, by week 120, resulting in net losses of 5.6% (SD: 8.9%) and 0.1% (SD: 5.8%), respectively, from week 0 to week 120. Cardiometabolic improvements seen from week 0 to week 68 with semaglutide reverted towards baseline at week 120 for most variables. Conclusions One year after withdrawal of once‐weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained two‐thirds of their prior weight loss, with similar changes in cardiometabolic variables. Findings confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health.

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Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined

Julie Lundgren, Charlotte Janus, Simon B.K. Jensen … (2021)

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Author and article information

Contributors

Marleen A. van Baak:

ORCID: https://orcid.org/0000-0003-2592-6363

m.vanbaak@maastrichtuniversity.nl

Journal

Journal ID (nlm-ta): Curr Obes Rep

Journal ID (iso-abbrev): Curr Obes Rep

Title: Current Obesity Reports

Publisher: Springer US (New York )

ISSN (Electronic): 2162-4968

Publication date (Electronic): 31 March 2025

Publication date PMC-release: 31 March 2025

Publication date (Print): 2025

Volume: 14

Issue: 1

Electronic Location Identifier: 28

Affiliations

[1 ]Department of Human Biology, NUTRIM Institute of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and life Sciences+, Maastricht University, ( https://ror.org/02jz4aj89) Maastricht, The Netherlands

[2 ]Department of Human Biology, NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University, ( https://ror.org/02jz4aj89) PO Box 616, Maastricht, 6200MD The Netherlands

Author information

Marleen A. van Baak https://orcid.org/0000-0003-2592-6363

Edwin C. M. Mariman https://orcid.org/0000-0002-5691-8633

Article

Publisher ID: 619

DOI: 10.1007/s13679-025-00619-x

PMC ID: 11958498

PubMed ID: 40163180

SO-VID: 53bc7fe6-bee9-4a06-a3cd-1b3169eea8fc

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date accepted : 17 March 2025

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ScienceOpen disciplines: Health & Social care

Keywords: obesity,lean mass,immune memory,gut microbiota,weight regain

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ScienceOpen disciplines: Health & Social care

Keywords: obesity, lean mass, immune memory, gut microbiota, weight regain

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Physiology of Weight Regain after Weight Loss: Latest Insights

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Abstract

Purpose of Review

Recent Findings

Summary

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Karger: Nutrition and Dietetics

Most cited references 40

Maintenance of Lost Weight and Long-Term Management of Obesity

Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension

Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined

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Most referenced authors 1,359