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

Abstract

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 30 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.