Efficacy and Safety of Metformin for Patients with Type 1 Diabetes Mellitus: A Meta-Analysis

BACKGROUND: Insulin is an essential therapy for patients with type 1 diabetes mellitus (T1DM). With the progression of the disease, many patients with T1DM may have an increased prevalence of insulin resistance; thus the common standard insulin therapy requires a high insulin dosage (>1 unit/kg/day) and is usually associated with many side effects. Studies have shown that metformin may benefit those insulin-resistant individuals with T1DM. This meta-analysis was performed to provide the evidence of clinical efficacy and safety of metformin in T1DM. MATERIALS AND METHODS: We conducted a search on Medline, EMBASE, and the Cochrane Library for relevant studies published before May 2014 based on "metformin" and "diabetes mellitus, type 1." The following outcomes were evaluated: hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), lipid metabolism, weight, insulin dosage, hypoglycemia, diabetic ketoacidosis, or gastrointestinal adverse events (AEs). The meta-analysis was performed using Review Manager version 5.2 software (The Nordic Cochrane Centre, Copenhagen, Denmark). RESULTS: In total, eight randomized controlled trials were included. Metformin was associated with a reduction in daily insulin dosage, body weight, total cholesterol level, low-density lipoprotein level, and high-density lipoprotein level but an increase in risk of gastrointestinal AEs compared with placebo treatment in T1DM patients. No significant difference was found between the metformin group and the placebo group in HbA1c level, FPG level, or triglycerides level. No significant difference was found between the metformin group and the placebo group in the risk of severe hypoglycemia or diabetic ketoacidosis. CONCLUSIONS: Metformin may decrease the daily insulin dosage, body weight, and lipid levels in T1DM. However, metformin does not increase the incidence of hypoglycemia and ketoacidosis. High-quality, large-sample, and long-term follow-up clinical trials are needed to confirm these conclusions.