Trial reportCirculation2022
Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study.
Trial report in Circulation, 2022. The graph read 1 number from its abstract, feeding 2 cells of the map, but it casts no vote: the report of the main result of NCT00004992 is not on the map. It reports registered trial NCT00004992. Cited by 84 papers, 1 of them a synthesis that pooled it.
What it found
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RESULTS: Neither metformin nor lifestyle intervention reduced the primary outcome: metformin versus placebo hazard ratio 1.03 (95% CI, 0.78-1.37; CONCLUSIONS: Neither metformin nor lifestyle reduced major cardiovascular events in DPPOS over 21 years despite long-term prevention of diabetes.
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What it adds to each cell
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Diet, exercise & lifestyle×cardiovascular events
Does not voteOpen on the map →What to test next →2 readable studies in this cell: 2 favour the treatment, 0 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
Metformin×cardiovascular events
Does not voteOpen on the map →What to test next →5 readable studies in this cell: 4 favour the treatment, 1 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Diabetes Prevention Program
Open the trial in the graphDiabetes Prevention Program Outcomes Study
Open the trial in the graphWho cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Physical Activity and Risk of Major Diabetes-Related Complications in Individuals With Diabetes: A Systematic Review and Meta-Analysis of Observational Studies.Diabetes care · 2022Pooled it
- Weight Loss Intervention Promoting an Adapted Mediterranean-Style Dietary Pattern: The DELISH Randomized Clinical Trial.JAMA network open · 2026Trial
- Trial
- Metformin Treatment With or Without Mediterranean Diet for the Prevention of Age-Related Diseases in People With Metabolic Syndrome: The MeMeMe Randomized Trial.Diabetes care · 2025Trial
- Semaglutide and Cardiovascular Outcomes by Baseline HbA1c and Change in HbA1c in People With Overweight or Obesity but Without Diabetes in SELECT.Diabetes care · 2024Trial
- Trial
- Coronary Artery Calcium and Cognitive Decline in the Diabetes Prevention Program Outcomes Study.Journal of the American Heart Association · 2023Trial
- Association of metformin with cardiovascular and graft outcomes in kidney transplant recipients with posttransplantation diabetes mellitus.Kidney research and clinical practice · 2026Article
- Associations between carotid macrovascular and retinal microvascular alterations in diabetes: Evidence synthesis and implications for risk assessment.Atherosclerosis plus · 2026Review
- Nutrition and Culinary Education in Food Is Medicine Interventions: A Scoping Review.Journal of the Academy of Nutrition and Dietetics · 2026Article
- The Look AHEAD Research Program: A 25-Year Retrospective From the Perspective of Geroscience.Diabetes care · 2026Review
- A cross-sectional analysis of baseline diet quality among participants enrolled in delicious eating for life in the southern homes weight loss randomized trial.Nutrition and health · 2026Article
- Efficacy of an Online Weight Loss Program for Mexican Adults: Findings From a Randomized Controlled Trial.Obesity science & practice · 2026Article
- Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Cardiovascular Disease Incidence in Adults With Prediabetes: Findings From the Diabetes Prevention Program.Journal of the American Heart Association · 2026Article
- Metformin Beyond Glycemic Control: Cardiovascular Protection and Diabetes Prevention.Journal of cardiovascular development and disease · 2026Review
- "Your Digital Doctor Will Now See You": A Narrative Review of VR and AI Technology in Chronic Illness Management.Healthcare (Basel, Switzerland) · 2026Review
- 3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes-2026.Diabetes care · 2026Review
- External validation and application of a machine learning-based model for diabetes progression in prediabetes.Frontiers in endocrinology · 2026Article
- Approaches for sustaining diabetes prevention program practices post-graduation: A scoping review.Preventive medicine reports · 2026Review
- Multimodal Therapeutic Strategies Targeting BCAA Metabolism in Diabetic Cardiomyopathy: A Path to Cardioprotection.Cardiovascular toxicology · 2025Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
The marked sentences are the ones the graph read a number from.
backgroundLifestyle intervention and metformin have been shown to prevent diabetes; however, their efficacy in preventing cardiovascular disease associated with the development of diabetes is unclear. We examined whether these interventions reduced the incidence of major cardiovascular events over a 21-year median follow-up of participants in the DPP trial (Diabetes Prevention Program) and DPPOS (Diabetes Prevention Program Outcomes Study).
methodsDuring DPP, 3234 participants with impaired glucose tolerance were randomly assigned to metformin 850 mg twice daily, intensive lifestyle or placebo, and followed for 3 years. During the next 18-year average follow-up in DPPOS, all participants were offered a less intensive group lifestyle intervention, and unmasked metformin was continued in the metformin group. The primary outcome was the first occurrence of nonfatal myocardial infarction, stroke, or cardiovascular death adjudicated by standard criteria. An extended cardiovascular outcome included the primary outcome or hospitalization for heart failure or unstable angina, coronary or peripheral revascularization, coronary heart disease diagnosed by angiography, or silent myocardial infarction by ECG. ECGs and cardiovascular risk factors were measured annually.
resultsNeither metformin nor lifestyle intervention reduced the primary outcome: metformin versus placebo hazard ratio 1.03 (95% CI, 0.78-1.37;
conclusionsNeither metformin nor lifestyle reduced major cardiovascular events in DPPOS over 21 years despite long-term prevention of diabetes. Provision of group lifestyle intervention to all, extensive out-of-study use of statin and antihypertensive agents, and reduction in the use of study metformin together with out-of-study metformin use over time may have diluted the effects of the interventions. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: DPP (NCT00004992) and DPPOS (NCT00038727).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.