Meta-Analysis of the Effect of Metformin on the Progression of Different Types of Prediabetes Mellitus.

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 adjust for potential confounders, variation in prediabetes diagnostic criteria across the publication years of the included studies, and heterogeneity in effect size comparisons. Overall, metformin may delay progression from prediabetes to T2DM, with the greatest observed benefit among individuals with IFG. Given the study heterogeneity and variability in diagnostic criteria, these findings should be interpreted cautiously. From a nursing and chronic disease prevention perspective, metformin may be considered as an adjunctive intervention for individuals with IFG when lifestyle intervention alone is insufficient.