Effects of Metformin Added to Insulin in Adolescents with Type 1 Diabetes: An Exploratory Crossover Randomized Trial

Abstract EN

Background.

To comprehensively assess the effects of metformin added to insulin on metabolic control, insulin sensitivity, and cardiovascular autonomic function in adolescents with type 1 diabetes.

Materials and Methods.

This was an exploratory, crossover, randomized trial conducted in adolescents with type 1 diabetes aged 12-18 years old.

Participants were randomly received metformin (≤1000 mg/d) added to insulin for 24 weeks followed by insulin monotherapy for a subsequent 24 weeks or vice versa.

Blood pressure, body mass index, insulin dose, estimated insulin sensitivity, glycated hemoglobin A1c (HbA1c), and lipid profiles were measured, with a 72-hour continuous glucose monitoring and 24-hour Holter monitoring performed at baseline, 24, and 50 weeks for the assessments of glucose variability and heart rate variability.

Results.

Seventeen patients with mean±SD age 14.4±2.3 years, body mass index 18.17±1.81 kg/m2, median (IQR) diabetes duration 4.50 (3.58, 6.92) years, and HbA1c 9.0% (8.5%, 9.4%) were enrolled.

The between-group difference in HbA1c of 0.28% (95% CI -0.39 to 0.95%) was not significant (P=0.40).

Changes in body mass index, insulin dose, blood pressure, lipid profiles, and estimated insulin sensitivity were similar for metformin add-on vs.

insulin monotherapy.

Glucose variability also did not differ.

Compared with insulin monotherapy, metformin add-on significantly increased multiple heart rate variability parameters.

Conclusions.

Metformin added to insulin did not improve metabolic control or glucose variability in lean/normal-weight adolescents with type 1 diabetes.

However, metformin added to insulin significantly increased heart rate variability, suggesting that metformin might improve cardiovascular autonomic function in this population.