A new clinical trial shows that metformin, an inexpensive drug used for type 2 diabetes for over 100 years, can help people with type 1 diabetes reduce their daily insulin requirements by about 12% while keeping blood sugar stable. The finding is surprising because metformin does not work the way researchers expected, pointing to a completely different mechanism that scientists are now racing to understand.

Why Does Insulin Reduction Matter for Type 1 Diabetes?

Type 1 diabetes is an autoimmune disease affecting more than 130,000 Australians, where the immune system attacks insulin-producing cells in the pancreas. People with this condition must take insulin for life to control their blood sugar levels. Managing the disease is demanding; people with type 1 diabetes make an estimated 180 additional daily decisions related to monitoring and adjusting their blood sugar.

Over time, some patients develop insulin resistance, meaning their bodies respond less effectively to insulin, requiring higher and higher doses. This creates a significant burden, both mentally and physically. Reducing the amount of insulin needed is a priority for many people living with type 1 diabetes, making this new finding particularly meaningful.

What Did the Clinical Trial Reveal?

Researchers at the Garvan Institute of Medical Research conducted the first randomized controlled trial of its kind, known as the Insulin Resistance in Type 1 Diabetes Managed with Metformin (INTIMET) study. The trial involved 40 adults with long-term type 1 diabetes who took either metformin or a placebo for six months.

The results defied 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," explained Dr. Jennifer Snaith, endocrinologist and co-lead of the study.

Dr. Jennifer Snaith, Endocrinologist at St Vincent's Hospital Sydney

How Does Metformin Actually Work in Type 1 Diabetes?

The mystery deepens when you consider that metformin's mechanism of action remains unknown, even after 100 years of use. Scientists expected the insulin reduction would come from improved insulin sensitivity, but the study showed that is not the case.

One leading hypothesis involves the gut microbiome, the community of bacteria living in your digestive system. Researchers suspect that metformin may influence gut bacteria in ways that affect how the body processes glucose. This avenue has never been studied before in people with type 1 diabetes.

"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," noted Dr. Snaith.

Dr. Jennifer Snaith, Endocrinologist at St Vincent's Hospital Sydney

Key Findings from the INTIMET Study

• Insulin Reduction: Participants taking metformin required approximately 12% less insulin than the placebo group while maintaining stable blood sugar levels.
• No Insulin Resistance Improvement: Contrary to initial expectations, metformin did not improve insulin resistance in people with type 1 diabetes, as measured by sophisticated clamp studies that map insulin resistance in different parts of the body.
• Blood Sugar Stability: No significant changes in blood sugar levels were observed between the metformin and placebo groups, indicating that the insulin reduction did not compromise glucose control.
• Cost and Accessibility: Metformin is an inexpensive, widely available medication that is already prescribed off-label to as many as 13,000 Australians with type 1 diabetes, making it a practical option if benefits are confirmed.

Steps to Understanding Metformin's Potential Role in Type 1 Diabetes Management

• Consult Your Endocrinologist: If you have type 1 diabetes and are interested in metformin, discuss this research with your doctor to determine whether it might be appropriate for your individual situation and insulin regimen.
• Monitor Your Insulin Requirements: If prescribed metformin, keep detailed records of your daily insulin doses and blood sugar readings to track any changes in your insulin needs over time.
• Stay Informed About Microbiome Research: Follow emerging research on how metformin affects the gut microbiome in type 1 diabetes, as this may lead to new insights about why the drug reduces insulin requirements.

The INTIMET study was published in Nature Communications and is supported by the Diabetes Australia Research Program, St Vincent's Clinic Research Foundation, and the National Health and Medical Research Council. While the exact mechanism remains unknown, this finding opens a new door for improving the daily lives of people with type 1 diabetes by potentially reducing their insulin burden without compromising blood sugar control.