Effect of metformin on insulin resistance in adults with type 1 diabetes: a 26-week randomized double-blind clinical trial
Jennifer Snaith, Nick Olsen, Jennifer A. Evans, Greg M. Kowalski, Clinton R. Bruce, Dorit Samocha‐Bonet, Samuel N. Breit, D. Jane Holmes–Walker, Jerry R. Greenfield
Abstract
Insulin resistance is an underrecognized cardiovascular risk factor in type 1 diabetes. The effect of metformin on insulin resistance in adults with type 1 diabetes is unknown. Forty adults with type 1 diabetes, and twenty adults without diabetes were studied in a baseline only cross-sectional study assessing insulin resistance using the two-step hyperinsulinemic-euglycemic clamp. Participants with type 1 diabetes exhibited hepatic (EGP 64% higher), muscle (glucose infusion rate [GIR] 29% lower) and adipose (higher non-esterified fatty acids [NEFA]) insulin resistance. We then conducted a parallel group randomized, placebo-controlled trial to assess the efficacy of metformin 1500 mg (n = 20) versus placebo (n = 20) in reducing insulin resistance in adults with type 1 diabetes over 26 weeks. The primary outcome was change in endogenous glucose production (EGP) during the low-dose phase of the clamp. Thirty seven of 40 adults with type 1 diabetes completed the study. At 26 weeks, there was no difference in change in EGP between metformin and placebo groups (mean difference 0.2 µmol/kg fat-free mass [FFM]/min [95%CI, -0.4 to 0.8 µmol/kgFFM/min]; p = 0.53). There was no increase in hypoglycemia or episodes of ketoacidosis in either group. These results do not support prescribing metformin to reduce hepatic insulin resistance in adults with type 1 diabetes. Australian New Zealand Clinical Trials Registry identifier, ACTRN12619001440112.