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A new clinical trial led by the Garvan Institute of Medical Research suggests that metformin, a widely used and inexpensive drug for type 2 diabetes, could help people with type 1 diabetes reduce how much insulin they need. The findings point to a potential new way to manage the condition more effectively.
For years, doctors have prescribed metformin to some people with type 1 diabetes in hopes of improving insulin resistance. That approach has mostly been based on limited evidence. Now, results from a controlled clinical trial show that while metformin does not improve insulin resistance in type 1 diabetes, it does help lower the amount of insulin required to keep blood sugar levels within a healthy range.
Published in Nature Communications, the study highlights a surprising benefit that could ease the daily challenges faced by people who rely on insulin therapy.
The Challenge of Managing Type 1 Diabetes
Type 1 diabetes is an autoimmune disease that affects more than 130,000 Australians. In this condition, the immune system attacks the insulin-producing cells in the pancreas. As a result, patients must take insulin for life to control their blood sugar.
Managing the disease can be demanding. People with type 1 diabetes make an estimated 180 additional daily decisions related to monitoring and adjusting their blood sugar levels.
Over time, some patients develop insulin resistance, meaning their bodies respond less effectively to insulin. This can lead to higher and higher doses being needed to maintain stable blood sugar.
“Insulin resistance is a growing problem in type 1 diabetes. Not only does it make regulating blood sugar levels difficult, but it is an underappreciated risk factor for heart disease, which is one of the biggest causes of health complications and deaths in those with type 1 diabetes,” says Dr. Jennifer Snaith, endocrinologist and co-lead of the study.
Clinical Trial Tests Metformin in Type 1 Diabetes
To better understand whether metformin could help, researchers conducted the first randomized controlled trial of its kind in adults with type 1 diabetes. The study, known as the Insulin Resistance in Type 1 Diabetes Managed with Metformin (INTIMET) study, examined whether the drug could reduce insulin resistance in this group.
Metformin is commonly used to treat type 2 diabetes and is already prescribed off-label to as many as 13,000 Australians with type 1 diabetes. However, its exact effects in this population have remained unclear.
“We randomized 40 adults with long-term type 1 diabetes to take either metformin or a placebo for six months. We examined whether their insulin resistance changed over that time through a sophisticated and comprehensive research technique, called a clamp study, that allowed us to map insulin resistance in different parts of the body,” explains Professor Greenfield.
Unexpected Results on Insulin Use
The results did not match expectations. Researchers found no improvement in insulin resistance and no significant changes in blood sugar levels among those taking metformin.
However, one key finding stood out. Participants who took metformin needed about 12% less insulin than those in the placebo group to maintain stable blood sugar.
“Although we didn’t find changes to insulin resistance from the use of metformin, we did show that people taking it used around 12% less insulin than those on placebo. This is an important result. Insulin is a relatively old treatment which, while lifesaving, comes with significant mental and physical burden. This means that lowering the amount of insulin used is a priority for many people living with type 1 diabetes. We have shown that a very cheap, accessible medication may serve this purpose and this is very exciting,” Dr. Snaith says.
Scientists Explore Possible Role of the Gut Microbiome
Researchers are now working to understand why metformin reduces insulin needs if it does not affect insulin resistance.
Professor Greenfield explains: “Metformin has been available in various forms for around 100 years, but it’s mechanism of action remains unknown. We would have expected that the observed reductions in insulin dose induced by metformin in our study would be due to the body becoming more sensitive to insulin, that is, becoming less insulin resistant. But we have shown that is not the case. Our priority is now working out how metformin is achieving this effect.”
One leading idea involves the gut microbiome. Scientists suspect that metformin may influence gut bacteria in ways that affect how the body processes glucose.
“There is increasing evidence suggesting that metformin may act on the gut. This is why we are now investigating how metformin changes gut flora, also known as the microbiome, in people with type 1 diabetes. This has not been studied before in type 1 diabetes. We’re hoping this will provide clues on metformin’s mechanism of action, so that it can be more widely used in the management of type 1 diabetes,” adds Dr. Snaith.
Funding and Research Team
This research is supported by the Diabetes Australia Research Program, St Vincent’s Clinic Research Foundation, UNSW Cardiac Vascular and Metabolic Medicine Theme, National Health and Medical Research Council, Melissa and Jonathon Green, and Dr. Leslie and Mrs Ginny Green.
Dr. Jennifer Snaith is an endocrinologist at St Vincent’s Hospital Sydney and post-doctoral research scientist. She is Clinical Lead of the Australian Collaborative Towards Adjunctive Therapies in Type 1 Diabetes (ACT-T1D)
Professor Jerry Greenfield is Faculty, Garvan Institute of Medical Research, Chair of ACT-T1D, Head of Department, Diabetes and Endocrinology, St Vincent’s Hospital, Sydney and Head of St Vincent’s Health Care Campus, Faculty of Medicine and Health, UNSW Sydney.
