Summary: In a 26-week double-blind trial, metformin did not reduce insulin resistance in adults with type 1 diabetes, with no difference in endogenous glucose production versus placebo, so the authors concluded the results do not support prescribing metformin for this purpose.
PICO Summary
| Element | Detail |
|---|---|
| Population | 40 adults with type 1 diabetes (plus 20 without diabetes in a baseline cross-sectional comparison); randomised double-blind trial with hyperinsulinaemic-euglycaemic clamp, Australia. |
| Intervention | Metformin 1500 mg daily for 26 weeks (n=20). |
| Comparison | Placebo for 26 weeks (n=20). |
| Outcome | At baseline, type 1 diabetes was associated with hepatic, muscle, and adipose insulin resistance versus non-diabetic controls. However, at 26 weeks there was no difference in the change in endogenous glucose production between metformin and placebo (mean difference 0.2 µmol/kg fat-free mass/min; 95% CI -0.4 to 0.8; p=0.53). There was no increase in hypoglycaemia or ketoacidosis. The authors concluded the results do not support prescribing metformin to reduce hepatic insulin resistance in type 1 diabetes. |
Metformin and insulin resistance in type 1 diabetes
RCT · type 1 diabetes · 26 weeks
Metformin did not reduce hepatic insulin resistance in type 1 diabetes, with endogenous glucose production unchanged versus placebo. The results do not support prescribing metformin for this purpose.
Expert Commentary
This is an important negative trial, and its findings must be read as such rather than as support for metformin. The study has two parts that should not be conflated. Its cross-sectional arm confirms something clinically real and useful, that adults with type 1 diabetes carry meaningful hepatic, muscle, and adipose insulin resistance compared with people without diabetes, the so-called double diabetes phenomenon. But its randomised arm, which is the part that tests the treatment question, found that metformin did not reduce the primary measure of hepatic insulin resistance, with the change in endogenous glucose production essentially identical to placebo at a clearly non-significant p of 0.53, and using gold-standard clamp methodology that should have detected a true effect. This is consistent with the larger REMOVAL trial, where metformin reduced weight and insulin dose but did not improve glycaemia or the primary vascular endpoint. Can I use this with my patients? It tells me what not to do: I would not add metformin specifically to improve insulin sensitivity in type 1 diabetes, since this rigorous trial shows it does not work for that purpose. Any residual role relates to modest weight or insulin-dose effects rather than correcting insulin resistance, and other adjuncts warrant separate evaluation.
References
Snaith JR, Olsen N, Evans J, et al. Effect of metformin on insulin resistance in adults with type 1 diabetes: a 26-week randomized double-blind clinical trial. Nat Commun. 2025;16(1):9884. doi:10.1038/s41467-025-65951-1