Meta-analysis of the effect of metformin on the regression of different types of prediabetes mellitus

OBJECTIVE To investigate the differences in the efficacy of metformin interventions for progression to type 2 diabetes in people with different subtypes of prediabetes (impaired fasting glucose, impaired glucose tolerance, mixed). MATERIALS AND METHODS Following the PRISMA guidelines, ten Chinese and English databases including PubMed and Cochrane were systematically searched (up to May 2025), and 18 randomized controlled trials were included in a meta-analysis using randomized/fixed-effects models to assess the effect of metformin versus lifestyle/placebo interventions on the incidence of type 2 diabetes, and to calculate the risk ratios (RR) and their 95% confidence intervals (CI), and subgroup analyses were performed based on prediabetes subtype and length of intervention. All statistical analyses were performed using Review Manager 5.4 software. RESULTS Eighteen RCTs were included and found a 35% lower risk of T2DM onset in the metformin group compared with the control group, compared with lifestyle change/placebo (RR = 0.65, 95% CI [0.55, 0.77], P < 0.00001), but there was moderate heterogeneity. Subgroup analysis of participants with different subtypes of prediabetes showed a 62% risk reduction (RR = 0.38, 95% CI [0.38, 0.61], P < 0.0001) for the IFG subtype with the best effect, and a 42% risk reduction (RR = 0.58, 95% CI [0.43, 0.79], P < 0.0004) for the IGT subtype; Mixed risk reduction was 23% (RR = 0.77, 95% CI [0.70, 0.86], P < 0.00001). In addition, intervention duration ≤ 24 months had a more significant effect on the IGT subtype (RR = 0.22, P < 0.0001); a higher proportion of the glycemic inverse metformin group returned to normoglycemia than the control group (RR = 1.80, 95% CI [1.39, 2.34], P < 0.0001). CONCLUSION Metformin can effectively delay the progression of prediabetes to type 2 diabetes, and the intervention effect on IFG subtypes was significantly better than that of IGT and mixed types, which may be related to the mechanism of drug targeting hepatic gluconeogenesis. It is recommended that combined metformin treatment be prioritized for the IFG population.