A randomized, placebo-controlled trial led by Australia’s Garvan Institute of Medical Research found that metformin, a long-used and low-cost drug for type 2 diabetes, did not improve clamp-measured insulin resistance in adults with type 1 diabetes but was associated with roughly 12% lower insulin requirements while blood sugar measures remained broadly unchanged.
Researchers in Sydney have reported results from a controlled clinical trial testing whether metformin—commonly prescribed for type 2 diabetes—can reduce insulin resistance in adults living with type 1 diabetes.
The study, called the Insulin Resistance in Type 1 Diabetes Managed with Metformin (INTIMET) trial, randomized 40 adults with long-term type 1 diabetes to take either metformin or placebo for 26 weeks (about six months). Investigators assessed insulin resistance using hyperinsulinemic-euglycemic “clamp” studies, a specialized method used to quantify insulin sensitivity in different tissues.
The findings, published in Nature Communications in 2025, showed no significant improvement in insulin resistance with metformin and no significant changes in blood sugar measures compared with placebo. However, participants assigned to metformin used about 12% less insulin than those receiving placebo while maintaining stable blood sugar levels.
Dr. Jennifer Snaith, an endocrinologist at St Vincent’s Hospital Sydney and a co-lead of the study, said insulin resistance is increasingly recognized in type 1 diabetes and can complicate glucose management. She also noted it is an underappreciated risk factor for heart disease, a major source of illness and death in people with type 1 diabetes.
Professor Jerry Greenfield, who holds senior diabetes and endocrinology roles at St Vincent’s Hospital Sydney and is affiliated with the Garvan Institute, said the team had expected any reduction in insulin dose to reflect improved insulin sensitivity, but clamp results did not support that explanation.
Researchers are now investigating other possible mechanisms, including whether metformin affects glucose metabolism through changes in the gut microbiome. The Garvan Institute noted that metformin is already used “off-label” in some people with type 1 diabetes in Australia, and it cited estimates that type 1 diabetes affects more than 130,000 Australians and can involve roughly 180 additional daily decisions related to glucose monitoring and insulin adjustment.
