Meta-Analysis of the Effect of Metformin on the Progression of Different Types of Prediabetes Mellitus
Abstract
This systematic review and meta-analysis aimed to examine the differential effects of metformin on progression to type 2 diabetes mellitus (T2DM) among individuals with different prediabetes subtypes, including impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG+IGT. Following PRISMA guidelines, ten databases, including PubMed and Cochrane, were systematically searched from inception to May 2025. Eighteen randomized controlled trials were included, and relative risks (RRs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models as appropriate. Subgroup analyses were conducted by prediabetes subtype and intervention duration. Metformin reduced the risk of progression to T2DM by 35% compared with lifestyle intervention or placebo (RR = 0.65; 95% CI: 0.55-0.77; P < 0.00001), with moderate heterogeneity. The preventive effect was strongest among individuals with IFG (RR = 0.38; 95% CI: 0.24-0.61; P < 0.0001), followed by those with IGT (RR = 0.58; 95% CI: 0.43-0.79; P < 0.0004) and combined IFG+IGT (RR = 0.77; 95% CI: 0.70-0.86; P < 0.00001). An intervention duration of ≤24 months was associated with a greater effect in the IGT subtype (RR = 0.27; 95% CI: 0.16-0.44; P < 0.00001). Metformin also increased the proportion of individuals achieving normoglycemia (RR = 1.80; 95% CI: 1.39-2.34; P < 0.0001). This study was limited by reliance on published aggregate data without individual patient-level information to…
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