Metformin might improve whole-body and peripheral insulin sensitivity in overweight/obese adolescents with type 1 diabetes (T1D), according to study results published in The Journal of Clinical Endocrinology & Metabolism.
Therapies targeting insulin resistance may be necessary in patients with T1D to lower the risk for cardiovascular complications, as intensive glucose control reduces but does not eliminate cardiometabolic diabetes complications. Researchers conducted this double-blind placebo-controlled clinical trial to evaluate the effects of metformin on insulin deficiency and resistance in muscle, hepatic, and adipose tissue in young patients with T1D. The researchers randomly assigned 37 patients with T1D (age 12 to 19 years; mean age, 15.7 years) and overweight/obesity from 8 sites to receive 3 months of daily metformin (≥1500 mg/d; n = 19) or placebo (n = 18). The participants underwent a 3-phase hyperinsulinemic-euglycemic clamp with glucose and glycerol isotope tracers before and after treatment.
Baseline characteristics were similar in both groups. Participants with diabetes were included if they had a body mass index ≥85th percentile for age and sex, a glycated hemoglobin level between 7.5% and 9.9%, and were taking a daily insulin dose ≥0.8 units/kg.
Compared with placebo, metformin yielded significantly greater improvements in both whole-body (change in glucose infusion rate, 1.3 mg/kg/min; P =.03) and peripheral insulin sensitivity (change in metabolic clearance rate, 0.923 dL/kg/min; P =.05) after 3 months.
However, metformin did not significantly affect insulin suppression of endogenous glucose release representing hepatic insulin sensitivity (P =.12) or glycerol release representing adipose insulin sensitivity (P =.69), the latter being deemed not accurately assessable with traditional methods.
Study limitations included its relatively small sample size and strict inclusion criteria.
“[W]e demonstrated that the addition of metformin to insulin therapy in overweight or obese youth with type 1 diabetes improves whole-body and specifically peripheral muscle [insulin deficiency and resistance] over a 13-week period,” the researchers said. “However, alternative approaches are likely needed to target the hepatic [insulin deficiency and resistance] of overweight/obese youth with type 1 diabetes.”
Cree-Green M, Bergman BC, Cengiz E, et al. Metformin improves peripheral insulin sensitivity in youth with type 1 diabetes [published online April 2, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2019-00129