Metformin as additional therapy in adolescents with poorly controlled type 1 diabetes:: randomised placebo-controlled trial with aspects on insulin sensitivity

Objective: Metabolic control often deteriorates during puberty in children with type 1 diabetes. The aim of the present study was to investigate whether addition of metformin for 3 months improves metabolic control and insulin sensitivity. Design: Twenty-six of 3 0 randomised adolescents with type 1 diabetes (18 females, eight males) completed a double-blind placebo-controlled trial. Their mean age was 16.9 +/- 1.6 (S.D.) years, mean glycated haemoglobin(HbA(1c)) 9.5 +/- 1.1% and daily insulin dosage 1.2 +/- 0.3 U/kg. The participants were randomised to receive oral metformin or placebo for 3 months. HbA(1C) was measured monthly, and peripheral insulin sensitivity was assessed by a euglycaemic hyperinsulinaemic clamp at baseline and at the end of the study. Results: HbA(1C) decreased significantly in the group treated with metformin, from 9.6 to 8.7% (P < 0.05), but was unchanged in the placebo group (9.5 vs 9.2%). Peripheral glucose uptake divided by mean plasma insulin concentration was increased in the metformin group (P < 0.05) but not in the placebo group. Initial insulin sensitivity was inversely correlated to changes in HbA(1C) (r = -0.62; P < 0.05) and positively correlated to changes in insulin sensitivity (r = 0.77; P < 0.01). Conclusions: In this double-blind placebo-controlled study we found that metformin improves metabolic control in adolescents with type 1 diabetes. The effect seems to be associated with an increased insulin-induced glucose uptake.