Clinical Question

Is metformin therapy more effective than therapeutic lifestyle changes in preventing progression to type 2 diabetes mellitus in patients with prediabetes?

Evidence-Based Answer

Metformin is more effective than standard lifestyle changes at preventing progression to type 2 diabetes. (Strength of Recommendation [SOR]: C, systematic review and meta-analysis of randomized controlled trials [RCTs] and RCT of disease-oriented outcomes.) [corrected] However, intensive lifestyle interventions are as effective as metformin. The effects of these interventions are enduring, with a continued benefit of intensive lifestyle interventions and metformin at 15 years of follow-up. (SOR: C, RCT of disease-oriented outcomes.) [correctred[ Patients with a body mass index (BMI) greater than 35 kg per m², age younger than 60 years, higher fasting glucose or A1C, or a history of gestational diabetes benefit the most from using metformin to prevent the progression from prediabetes to type 2 diabetes. (SOR: C, RCT of disease-oriented outcomes.) [corrected]

Evidence Summary

A 2019 Cochrane review of 20 RCTs studied metformin for diabetes prevention for a follow-up period of one to three years.¹ The metformin dosage varied drastically in these trials, from 38 mg per day to 3,000 mg per day. A total of 12 RCTs (n = 3,632) evaluated the incidence of type 2 diabetes in patients randomized to metformin therapy compared with those randomized to placebo or standard care (i.e., physician recommendations about healthy diet and exercise). These trials found that metformin was more effective (relative risk [RR] = 0.50; 95% CI, 0.38 to 0.65; P < .001). Seven RCTs (n = 2,960) compared the incidence of type 2 diabetes in patients randomized to metformin vs. intensive diet and lifestyle modification (defined differently among studies, but often including at least 30 minutes of exercise per day and structured visits with a dietitian). There was no significant difference between the two groups (RR = 0.80; 95% CI, 0.47 to 1.37; P = .42).