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Randomized Study of Metformin and Intensive Lifestyle Intervention on Cancer Incidence over 21 years of follow-up in the Diabetes Prevention Program

Mené sur 3 424 personnes présentant un risque élevé de développer un diabète (durée médiane de suivi : 21 ans), cet essai randomisé analyse l'association entre une utilisation de metformine ou des modifications profondes du mode de vie et le risque de cancer

Meta-analyses have reported a decrease in overall cancer incidence of approximately 10-40% with metformin use among individuals with diabetes. Lifestyle change could potentially reduce cancer incidence. The objective was to determine whether metformin or intensive lifestyle intervention (ILS) reduces the risk of cancer among adults at high risk of diabetes. The Diabetes Prevention Program (DPP, 1996-2001) randomized 3234 participants to ILS, metformin (850 mg twice daily), or blinded placebo. During follow-up through the DPP Outcomes Study (DPPOS), all participants were offered a modified lifestyle intervention, and metformin continued open-label metformin group. Participants reported cancer cases annually. Medical records were adjudicated for all reported events. The primary endpoint was total cancer incidence, comparing metformin versus placebo, with ILS versus placebo as a secondary objective. After a median follow-up of 21 years, 546 participants (173 metformin, 182 ILS, and 191 placebo) were diagnosed with a first incident cancer. Incidence rates of cancer were 9.8, 10.5, and 10.8 per 1,000 person-years in metformin, ILS, and placebo, respectively, with a hazard ratio (HR) of 0.90 (95%CI = 0.73 to 1.10) for metformin compared to placebo and 0.96 (95%CI = 0.79 to 1.18) for ILS compared to placebo. There were no differences between any treatment groups for obesity-related cancer or in sex-specific analyses. Neither assignment to metformin nor ILS reduced cancer incidence among adults at high risk of diabetes. These results may be impacted by increased non-study metformin usage over time due to the development of diabetes and reduced intensity of ILS intervention over time.

Cancer Prevention Research , résumé 2025

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