Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes

J Clin Endocrinol Metab. 2019 Aug 1;104(8):3265-3278. doi: 10.1210/jc.2019-00129.


Context: Type 1 diabetes in adolescence is characterized by insulin deficiency and insulin resistance (IR), both thought to increase cardiovascular disease risk. We previously demonstrated that adolescents with type 1 diabetes have adipose, hepatic, and muscle IR, and that metformin lowers daily insulin dose, suggesting improved IR. However, whether metformin improves IR in muscle, hepatic, or adipose tissues in type 1 diabetes was unknown.

Objective: Measure peripheral, hepatic, and adipose insulin sensitivity before and after metformin or placebo therapy in youth with obesity with type 1 diabetes.

Design: Double-blind, placebo-controlled clinical trial.

Setting: Multi-center at eight sites of the T1D Exchange Clinic Network.

Participants: A subset of 12- to 19-year-olds with type 1 diabetes (inclusion criteria: body mass index ≥85th percentile, HbA1c 7.5% to 9.9%, insulin dosing ≥0.8 U/kg/d) from a larger trial (NCT02045290) were enrolled.

Intervention: Participants were randomized to 3 months of metformin (N = 19) or placebo (N = 18) and underwent a three-phase hyperinsulinemic euglycemic clamp with glucose and glycerol isotope tracers to assess tissue-specific IR before and after treatment.

Main outcome measures: Peripheral insulin sensitivity, endogenous glucose release, rate of lipolysis.

Results: Between-group differences in change in insulin sensitivity favored metformin regarding whole-body IR [change in glucose infusion rate 1.3 (0.1, 2.4) mg/kg/min, P = 0.03] and peripheral IR [change in metabolic clearance rate 0.923 (-0.002, 1.867) dL/kg/min, P = 0.05]. Metformin did not impact insulin suppression of endogenous glucose release (P = 0.12). Adipose IR was not assessable with traditional methods in this highly IR population.

Conclusions: Metformin appears to improve whole-body and peripheral IR in youth who are overweight/obese with type 1 diabetes.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adolescent
  • Adult
  • Blood Glucose / analysis
  • Child
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance*
  • Liver / metabolism
  • Male
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Young Adult


  • Blood Glucose
  • Hypoglycemic Agents
  • Metformin

Associated data