Lifestyle and Metformin Interventions and Risk of Multimorbidity in Adults With Prediabetes
Abstract
Importance: Studying how to prevent or delay not just 1 disease but multiple chronic conditions is of great importance for public health; however, few interventions have demonstrated success during long-term follow-up.
Objective: To examine the association of lifestyle or metformin compared with placebo on long-term multimorbidity in adults with prediabetes.
Design, setting, and participants: Observational follow-up cohort study of a randomized clinical trial conducted at 27 sites in the United States from June 1, 1996, to December 31, 2021. From June 1, 1996, through May 28, 1999, 3234 adults at high risk of diabetes enrolled in the 3-year Diabetes Prevention Program (DPP). They were subsequently enrolled in the DPP Outcomes Study (DPPOS). Of this cohort, Centers for Medicare & Medicaid Services (CMS) morbidity data were available through 2021 for 1173 participants who provided consent. Data were analyzed from June 5, 2024, to November 7, 2025.
Exposures: Participants in DPP were randomly assigned to intensive lifestyle intervention, metformin, or placebo. During DPPOS, medications were unmasked with discontinuation of placebo; metformin was continued. Group booster classes were offered to the lifestyle group semiannually and all participants were offered lifestyle classes quarterly until 2014.
Main outcomes and measures: The primary outcome was multimorbidity (presence of ≥2 of 15 prevalent conditions, defined in CMS' Chronic Condition Data Warehouse and adapted for…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 1,173 participants or records.
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