Metformin’s Overall Effectiveness and Combined Action with Lifestyle Interventions in Preventing Type-2 Diabetes Mellitus in High-Risk Metformin-Naïve Patients: An Updated Systematic Review and Meta-Analysis of Published RCTs
Abstract
Background: The effectiveness of metformin in preventing Type-2 Diabetes Mellitus (T2DM) is examined. There are new available data. Currently, there are no available analyses classifying its effectiveness compared to placebo, standard care, or lifestyle interventions, and there is limited evidence on the combined action of metformin and lifestyle interventions in preventing T2DM. Objective: To calculate the updated overall effectiveness of metformin in preventing T2DM using all available and most recent data, and to explore the effectiveness of metformin and lifestyle interventions in preventing T2DM. Materials and Methods: A search was performed in PubMed and the Cochrane Library Central Register of Controlled Trials (CENTRAL) (from inception to 24 May 2025). A systematic review (SR) and meta-analysis (MA) of randomized controlled trials (RCTs) was carried out, including metformin-naïve adults with any identified diabetes risk factors. The overall effectiveness of metformin was estimated by combining studies that compare metformin against placebo, metformin and standard care against standard care, and metformin plus lifestyle interventions and the same lifestyle interventions. The combined action of metformin and lifestyle interventions was evaluated against standard care. We performed a GRADE assessment of the overall evidence. Results: Overall, metformin may reduce the incidence of T2DM by 23% in high-risk adults (OR 0.77, 95% CI 0.67, 0.88, p-value 0.0001) and 25% in…
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