Change in cardiometabolic risk factors associated with magnitude of weight regain 3 years after a 1-year intensive lifestyle intervention in type 2 diabetes mellitus: the Look AHEAD trial.
Open accessAbstract
Background: Weight regain after weight loss is common. The impact on cardiometabolic risk factors is not well established. Methods and Results: Publicly available data were analyzed from participants of the Look AHEAD (Action for Health in Diabetes) trial with ≥3% initial weight loss (n=1561) during a 1‐year intensive lifestyle intervention and with year 4 follow‐up data. Participants who regained (regainers) or maintained (maintainers) weight loss were defined with 5 dichotomized cut points (0%, 25%, 50%, 75%, and 100%) of percentage weight loss regained (weight change from years 1–4 as percentage of first year weight loss). Change in cardiometabolic risk factors after initial weight loss was compared in maintainers and regainers, after controlling for demographics, medications, and baseline and year 1 change in body mass index. The effect was assessed separately in participants with <10% and ≥10% initial weight loss, and women and men. Maintainers exhibited significant improvements to the cardiometabolic risk factors assessed compared with regainers. No weight regain cut point maximized risk difference between maintainers and regainers across risk factors or sex/initial weight loss subgroups. For many risk factors, allowing more regain as part of maintenance (increasing cut point) diminished the cardiometabolic benefit among maintainers. Conclusions: Maintaining weight loss was better than regain for all risk factors. No single cut point maximized the risk difference between maintainers and regainers. Maintainers who kept off ≥75% of weight lost had the greatest benefit. These findings emphasize the importance of intervention programs focusing not only on weight loss but weight loss maintenance, given the adverse consequences of the latter. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00017953.
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Weight regain of 25% or more of initial weight reduction has clinical relevance given the evidence to date suggesting the loss of cardiometabolic benefit at or beyond this level of weight regain.
“Weight regain of 25% or more of initial weight reduction has clinical relevance given the evidence to date suggesting the loss of cardiometabolic benefit at or beyond this level of weight regain.”
From Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial (2026) · cites this paper as [10]
The observation that greater weight regain on tirzepatide withdrawal was associated with greater reversal of cardiometabolic improvements is consistent with findings from lifestyle intervention in the Look AHEAD trial and with withdrawal of semaglutide, 2.4 mg, in the STEP 1 trial extension.
“This observation is consistent with the findings observed with lifestyle intervention in the Look AHEAD trial10 and with the withdrawal of glucagon-like peptide-1 receptor agonist semaglutide, 2.4 mg, in the STEP 1 trial extension.11”
From Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial (2026) · cites this paper as [10]
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Obesity and the risk of cardiometabolic diseases
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- Authors
- Berger, S. E., Huggins, G. S., McCaffery, J. M., Jacques, P. F., & Lichtenstein, A. H.
- Affiliations
- Tufts University (US)
- University of Connecticut (US)
- Corresponding author
- Lichtenstein, Alice H.
- Venue
- Journal of the American Heart Association
- Published
- 2019-10-15
- Volume
- 8
- Issue
- 20
- Pages
- e010951-e010951
- ISSN
- 2047-9980 (ISSN-L)
- PMC
- PMC6818027
- OpenAlex
- W2980059388
- Cited by
- 41
- References
- 25
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 2 · 2023: 9 · 2022: 8 · 2021: 3 · 2020: 6 · 2019: 2
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK057149, U01DK057151, U01DK057131, U01DK057182, U01DK057154, U01DK057008, U01DK057171, U01DK057002, U01DK057219, P30DK111022)
- National Center for Research Resources (M01RR000043)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
- Keywords
- weight regain, weight loss maintenance, type 2 diabetes, cardiometabolic risk factors, intensive lifestyle intervention, Look AHEAD trial, body mass index, sex differences
- MeSH terms
- Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Humans, Life Style, Male, Middle Aged, Obesity, Prognosis, Risk Factors, Weight Gain, Weight Loss, Body Mass Index, Risk Reduction Behavior
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