Metformin plus lifestyle interventions versus lifestyle interventions alone for the delay or prevention of type 2 diabetes in individuals with prediabetes: a meta-analysis of randomized controlled trials

Objectives: We conducted this meta-analysis of randomized controlled trials (RCTs) to compare the efficacy of adding metformin to lifestyle interventions versus lifestyle interventions alone in individuals with prediabetes.

Materials and methods: We searched four databases from inception until March 20, 2024. Our primary outcomes included the incidence of type 2 diabetes, hemoglobin A1c (HbA1c), and fasting plasma glucose (FPG). Secondary outcomes included blood pressure, plasma lipids, and weight measurements. Dichotomous outcomes were pooled as the risk ratio (RR) and its 95% confidence interval (CI), while continuous outcomes were pooled as the standardized mean difference (SMD) and its 95% CI in the random effect model. All statistical analyses were conducted using the "meta" package of RStudio software.

Results: We included 12 RCTs, comprising 2720 patients. Adding metformin to lifestyle interventions significantly reduced HbA1c levels (SMD = -0.10, 95% CI [-0.19, -0.01], P = 0.03) and the incidence of type 2 diabetes (RR = 0.85, 95% CI [0.75, 0.97], P = 0.01). Interestingly, adding metformin to lifestyle interventions was comparable to lifestyle interventions alone in terms of FPG at both 3 and 6 months; however, it significantly reduced FPG at 12 months (SMD = -0.34, 95% CI [-0.59, -0.08], P = 0.01). There were no significant differences between the two groups in terms of all secondary outcomes.

Conclusions: Our findings suggest that adding metformin to lifestyle interventions may improve glycemic control in individuals with prediabetes and reduce their risk of progression to diabetes, compared to lifestyle interventions alone. A longer duration of this combined approach may be required to observe the desired effects.