Association of weight loss maintenance and weight regain on 4-year changes in CVD risk factors: the Action for Health in Diabetes (Look AHEAD) clinical trial.
Open accessAbstract
OBJECTIVE: Short-term weight loss improves cardiovascular disease (CVD) risk factors. We sought to determine the longer-term effects of maintaining weight loss or, conversely, regaining weight. RESEARCH DESIGN AND METHODS: We used data from Action for Health in Diabetes (Look AHEAD), a randomized trial of intensive lifestyle intervention (ILI) compared to a control condition in overweight/obese individuals with type 2 diabetes. ILI participants were grouped according to weight change patterns, as follows: 1) no weight loss (±3% at years 1 and 4); 2) moderate weight loss (3–8% at years 1 and 4); 3) large weight loss (8–20% at years 1 and 4); 4) moderate loss/full regain (3–8% at year 1/±3% at year 4); 5) large loss/full regain (8–20% at year 1/± 3% year 4); and 6) large loss/partial regain (8–20% at year 1/3–8% at year 4) and changes in CVD risk factors were compared. RESULTS: Adjusting for baseline differences and medication use, larger weight losses produced greater improvements in HbA1c, systolic blood pressure, HDL cholesterol, and triglycerides at years 1 and 4 (all P ≤ 0.02). Despite maintenance of weight loss, HbA1c levels worsened between years 1 and 4, and remained below baseline only in those with large weight losses. We found no negative associations of losing and regaining weight relative to not having lost weight. Moreover, those who had large initial weight loss but full regain of weight had greater improvements in HbA1c levels at year 4 than those with smaller or no initial weight loss. CONCLUSIONS: Larger initial weight loss should be encouraged in individuals with type 2 diabetes, despite the possibility of regain.
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Weight regain after discontinuing weight loss interventions, regardless of modality of weight loss, has been demonstrated.
“Weight regain after discontinuing weight loss interventions, regardless of modality of weight loss, has been demonstrated”
From Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial (2026) · cites this paper as [4]
The Abstract (page unavailable) says weight regain is common after behavioral treatment, even with ongoing treatment contact. The Intervention section (page unavailable) describes a lifestyle intervention; the paper does not establish regain specifically after discontinuation or regardless of weight-loss modality. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn that analysis, large initial weight losses followed by partial or full regain by year 4 were associated with a sustained benefit on HbA1c at year 4 relative to that seen in participants with smaller or no initial weight loss.
“In that analysis, large initial weight losses followed by partial or full regain by year 4 were associated with a sustained benefit on HbA1c at year 4 relative to that seen in participants with smaller or no initial weight loss.”
From Weight regain and cardiometabolic effects after withdrawal of semaglutide: The <scp>STEP</scp> 1 trial extension (2022) · cites this paper as [25]
Previously, a post hoc analysis of the Look AHEAD trial explored the effects of weight regain on cardiometabolic risk factors among people with overweight/obesity and type 2 diabetes who received intensive lifestyle intervention.
“Previously, a post hoc analysis of the Look AHEAD trial explored the effects of weight regain on cardiometabolic risk factors among people with overweight/obesity and type 2 diabetes who received intensive lifestyle intervention.”
From Weight regain and cardiometabolic effects after withdrawal of semaglutide: The <scp>STEP</scp> 1 trial extension (2022) · cites this paper as [25]
These findings support the importance of long-term maintenance of weight reduction through lifestyle intervention and obesity management medications to sustain cardiometabolic benefits and improved health-related quality of life.
“these findings support the importance of long-term maintenance of weight reduction through lifestyle intervention and obesity management medications to sustain cardiometabolic benefits and improved health-related quality of life.”
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 [21]
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References 31 · Cited by 125
- Authors
- The Action for Health in Diabetes (Look AHEAD) Study Group
- Corresponding author
- The Action for Health in Diabetes (Look AHEAD) Study Group
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2016-06-06
- Volume
- 39
- Issue
- 8
- Pages
- 1345-1355
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC4955927
- OpenAlex
- W2560962203
- Cited by
- 125
- References
- 31
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 15 · 2023: 11 · 2022: 16 · 2021: 14 · 2020: 16 · 2019: 12 · 2018: 8 · 2017: 10 · 2016: 3
- FWCI
- 11.05
- Type
- journal article
- Language
- en
- Update notices
- correction (2016-12-01)
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK56990, DK56992, DK57002, DK57008, DK57078, DK57131, DK57135, DK57136, DK57149, DK57151, DK57154, DK57171, DK57177, DK57178, DK57182, DK57219)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- weight loss maintenance, weight regain, cardiovascular risk factors, type 2 diabetes, intensive lifestyle intervention, HbA1c, blood pressure, HDL cholesterol, triglycerides, obesity, Look AHEAD trial
- MeSH terms
- Body Weight Maintenance, Aged, Blood Pressure, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Life Style, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Obesity, Risk Factors, Triglycerides, Weight Gain, Weight Loss, Body Mass Index, Logistic Models, Overweight
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