Metformin improves peripheral insulin sensitivity in overweight adolescents with T1D
Treatment with metformin may improve whole-body and peripheral insulin resistance (IR) in youth who are overweight/obese with type 1 diabetes (T1D), according to a study.
This double-blind, multicentre, placebo-controlled clinical trial was conducted at eight sites of the T1D Exchange Clinic Network and included a subset of individuals aged 12–19 years with T1D from a larger trial. The inclusion criteria were body mass index ≥85th percentile, HbA1c 7.5–9.9 percent and insulin dosing ≥0.8 U/kg/d.
Participants were randomly assigned to 3 months of metformin (n=19) or placebo (n=18) and underwent a three-phase hyperinsulinaemic euglycaemic clamp with glucose and glycerol isotope tracers to examine tissue-specific IR before and after treatment.
The authors measured peripheral insulin sensitivity, endogenous glucose release and lipolysis rate before and after metformin or placebo therapy.
Differences in change in insulin sensitivity were detected in favour of the metformin vs the placebo arm vis-à-vis whole-body IR (change in glucose infusion rate, 1.3 mg/kg/min, 0.1–2.4; p=0.03) and peripheral IR (change in metabolic clearance rate, 0.923 dL/kg/min, –0.002 to 1.867; p=0.05).
Metformin showed no influence on insulin suppression of endogenous glucose release (p=0.12). In addition, adipose IR could not be measured with traditional methods in this highly IR population.
“T1D in adolescence is characterized by insulin deficiency and IR, both thought to increase cardiovascular disease risk,” the authors said. “We previously demonstrated that adolescents with T1D have adipose, hepatic and muscle IR, and that metformin lowers daily insulin dose, suggesting improved IR.”