The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial
Open accessAbstract
BACKGROUND: The metabolic syndrome is a high-risk state for diabetes and cardiovascular disease. Little is known about its prevalence and prevention in those with impaired glucose tolerance. OBJECTIVE: To determine the prevalence of the metabolic syndrome at baseline in the Diabetes Prevention Program and the effect of intensive lifestyle intervention and metformin therapy on the syndrome's incidence and resolution. DESIGN: Randomized, controlled clinical trial. SETTING: Research and community-based centers. PARTICIPANTS: Participants had impaired glucose tolerance (World Health Organization criteria plus fasting plasma glucose level >or=5.3 mmol/L [>or=95 mg/dL]) and were followed for a mean of 3.2 years after random assignment to intensive lifestyle intervention, metformin therapy, or placebo. INTERVENTIONS: Metformin, 850 mg twice daily, or intensive lifestyle intervention designed to achieve and maintain a 7% weight loss and 150 minutes of exercise per week. MEASUREMENTS: The metabolic syndrome was defined as having 3 or more characteristics (waist circumference; blood pressure; and levels of high-density lipoprotein cholesterol, triglycerides, and fasting plasma glucose) that met criteria from the National Cholesterol Education Program Adult Treatment Panel III. RESULTS: Fifty-three percent of participants (n = 1711) had the metabolic syndrome at baseline; incidence did not vary substantially by age. However, low levels of high-density lipoprotein cholesterol predominated in younger participants (age 25 to 44 years), and high blood pressure predominated in older participants (age 60 to 82 years). In life-table analyses (log-rank test), incidence of the metabolic syndrome was reduced by 41% in the lifestyle group (P < 0.001) and by 17% in the metformin group (P = 0.03) compared with placebo. Three-year cumulative incidences were 51%, 45%, and 34% in the placebo, metformin, and lifestyle groups, respectively. There was no significant heterogeneity by ethnic group. LIMITATIONS: The study involved a volunteer group with impaired glucose tolerance, which limits generalizability. CONCLUSIONS: The metabolic syndrome affected approximately half of the participants in the Diabetes Prevention Program at baseline. Both lifestyle intervention and metformin therapy reduced the development of the syndrome in the remaining participants.
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Metformin reduces insulin levels, inflammation and thrombosis, and the risk of metabolic syndrome, and improves insulin sensitivity, suggesting its potential to exert protective effects on cognitive function.
“Studies showing that metformin (MET) not only reduces insulin levels (11), inflammation and thrombosis (12), and the risk of the metabolic syndrome (13), but also improves insulin sensitivity (11) suggests its potential to exert protective effects on cognitive function.”
From Type 2 Diabetes and Antidiabetic Medications in Relation to Dementia Diagnosis (2014) · cites this paper as [13]
In the Look AHEAD Trial, weight reduction translated into appreciable triglyceride lowering.
“Similar results were reported in the Look AHEAD (Action for Health in Diabetes) Trial, 438 in which weight reduction also translated into appreciable triglyceride lowering.”
From Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association (2011) · cites this paper as [438]
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The Diabetes Prevention Program Outcomes Study Research Group; prepared on behalf of the DPPOS Research Group, Orchard, T. J., Temprosa, M., Barrett‐Connor, E., Fowler, S. E., Goldberg, R. B., Mather, K. J., Marcovina, S. M., Montez, M., Ratner, R. E., et al. (2013) · Diabetic Medicine · doi:10.1111/j.1464-5491.2012.03750.x · Cited by 214 · see citing works
Self-citation
- Authors
- Orchard, T. J., Temprosa, M., Goldberg, R., Haffner, S., Ratner, R., Marcovina, S., Fowler, S., & for the Diabetes Prevention Program Research Group
- Affiliations
- George Washington University (US)
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2005-04-19
- Volume
- 142
- Issue
- 8
- Pages
- 611-619
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- PMC
- PMC2505046
- OpenAlex
- W2065827854
- Cited by
- 948
- References
- 26
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 19 · 2023: 16 · 2022: 19 · 2021: 24 · 2020: 26 · 2019: 28 · 2018: 38 · 2017: 33 · 2016: 37 · 2015: 52 · 2014: 41 · 2013: 57 · 2012: 56
- FWCI
- 55.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK048489)
- 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 › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- metabolic syndrome, metformin, intensive lifestyle intervention, impaired glucose tolerance, type 2 diabetes prevention, prevalence, incidence, HDL cholesterol, blood pressure, weight loss, physical activity, Diabetes Prevention Program
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Diet, Reducing, Exercise Therapy, Humans, Hypoglycemic Agents, Life Style, Metformin, Middle Aged, Risk Factors, United States, Incidence, Metabolic Syndrome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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