The use of metformin in type 1 diabetes: a systematic review of efficacy.

Aims/hypothesis: As adding metformin to insulin therapy has been advocated in type 1 diabetes, we conducted a systematic review of published clinical trials and clinical trial databases to assess the effects on HbA(1c), weight, insulin-dose requirement and adverse effects.

Methods: We constructed evidence tables and fitted a fixed-effects model (inverse variance method) in order to assess heterogeneity between studies and give a crude measure of each overall treatment effect.

Results: Of 197 studies identified, nine involved randomisation with informed consent of patients with type 1 diabetes to metformin (vs placebo or comparator) in either a parallel or crossover design for at least 1 week. We noted marked heterogeneity in study design, drug dose, age of participants and length of follow-up. Metformin was associated with reductions in: (1) insulin-dose requirement (5.7-10.1 U/day in six of seven studies); (2) HbA(1c) (0.6-0.9% in four of seven studies); (3) weight (1.7-6.0 kg in three of six studies); and (4) total cholesterol (0.3-0.41 mmol/l in three of seven studies). Metformin was well tolerated, albeit with a trend towards increased hypoglycaemia. Formal estimates of combined effects from the five trials which reported appropriate data indicated a significant reduction in insulin dose (6.6 U/day, p < 0.001) but no significant reduction in HbA(1c) (absolute reduction 0.11%, p = 0.42). No reported trials included cardiovascular outcomes.

Conclusions/interpretation: Metformin reduces insulin-dose requirement in type 1 diabetes but it is unclear whether this is sustained beyond 1 year and whether there are benefits for cardiovascular and other key clinical outcomes.