Does Metformin Therapy Influence the Effects of Intensive Lifestyle Intervention? Exploring the Interaction Between First Line Therapies in the Look AHEAD Trial
Abstract
Aims Metformin and lifestyle intervention are frequently prescribed together as first-line treatments for type 2 diabetes. However, little is known about their interplay. We investigated if the effects of a lifestyle intervention on glycemia, body mass and cardiorespiratory fitness (CRF) were influenced by metformin therapy.Methods Participants randomized to intensive lifestyle intervention (ILI) or diabetes support and education (DSE) from the Look AHEAD trial were categorized into metformin therapy vs. no metformin. A two-by-two ANCOVA (i.e., metformin therapy vs. no metformin by ILI vs. DSE) was used to examine the changes in glycated hemoglobin A1C, fasting plasma glucose (FPG), body mass, and CRF over the first year post-randomization, with a primary interest in the metformin-by-lifestyle interaction effect.Results Data from 1982 participants were analyzed. There was a significant metformin-by-lifestyle interaction effect on A1C (p = 0.031) and FPG (p = 0.043), resulting from larger reductions associated with metformin therapy compared to no metformin following DSE, but slightly smaller reduction associated with metformin therapy compared to no metformin following ILI. Metformin therapy was associated with smaller weight loss (-4.7 ± 6.2 vs. -5.7 ± 6.3 kg; main effect: p = 0.001) but not with differential CRF changes when compared to no metformin.Conclusions The interaction between metformin therapy and lifestyle intervention on glycemia highlights the complicated nature of combining therapies. While the small influence of background metformin therapy on intensive lifestyle intervention should not discourage the concomitant use of these therapies, our results showed that, for individuals undergoing intensive lifestyle therapy, background metformin therapy conferred little additional benefits.
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Based on data from the Look AHEAD randomized intensive lifestyle intervention trial, metformin provided minimal additional benefit.
“Comparable conclusions were reached based on the data from the Look AHEAD randomized intensive lifestyle intervention trial that metformin provided minimal additional benefit (204).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [204]
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- Authors
- Terada, T., & Boulé, N. G.
- Affiliations
- Ottawa Heart Institute (CA)
- University of Alberta (CA)
- Corresponding author
- Boulé, Normand G.
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 94
- Pages
- 39-46
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2909335073
- Cited by
- 15
- References
- 36
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 1
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Nursing Research
- National Heart, Lung, and Blood Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute on Minority Health and Health Disparities
- Office of Research on Women's Health
- Centers for Disease Control and Prevention
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- metformin, intensive lifestyle intervention, type 2 diabetes, Look AHEAD trial, HbA1c, fasting blood glucose, glycemic control, weight loss, cardiorespiratory fitness, diabetes support and education, combination therapy, drug interactions
- MeSH terms
- Cardiorespiratory Fitness, Blood Glucose, Diabetes Mellitus, Type 2, Glycated Hemoglobin, Humans, Life Style, Metformin, Weight Loss, Body Mass Index, Treatment Outcome
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