100-year-old medication could improve life for people with type 1 diabetes

By Stephen Beech

A cheap, century-old medication can improve life for people with type 1 diabetes, according to new research.

A clinical trial in Australia found that the type 2 diabetes drug metformin reduces insulin needs in type 1 diabetes.

The discovery opens doors for improved management of the condition, say scientists.

Type 1 diabetes is a common condition - affecting around 450,000 people in the UK - in which the immune system incorrectly attacks the insulin-producing cells of the pancreas.

As a result, people with type 1 diabetes need to administer insulin for the rest of their lives to regulate blood sugar levels.

In some people with type 1 diabetes, long-term insulin use can lead to insulin resistance, where the body’s cells no longer respond effectively to the drug, meaning they need ever-increasing amounts of insulin to keep blood sugar levels under control.

For years, doctors have prescribed metformin to treat insulin resistance in type 1 diabetes, largely based on anecdotal evidence.

Now the clinical trial has found that metformin doesn't counteract insulin resistance in type 1 diabetes, but instead reduces the amount of insulin needed to maintain blood sugar levels in the ideal range.

The surprising findings, published in the journal Nature Communications, could improve how doctors manage type 1 diabetes and ease the burden that people with the condition face when using insulin alone.

Study co-leader Dr. Jennifer Snaith, of the Garvan Institute of Medical Research, said: "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.”

A Garvan team led by Dr. Snaith and Dr. Jerry Greenfield undertook the world’s first randomized controlled trial in adults testing whether metformin - normally used to counteract insulin resistance in type 2 diabetes - could do the same in type 1 diabetes.

Dr. Greenfield said: “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."

The team were surprised to find that the use of metformin did not lead to improvements in insulin resistance or changes to blood sugar levels.

They said that suggests that, unlike for type 2 diabetes, metformin does not work to counter insulin resistance in type 1 diabetes.

However, metformin did decrease the amount of insulin people needed to keep their blood sugars stable.

Dr. Snaith said: “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 that, 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.”

The team is now investigating how metformin may work to lower the amount of insulin needed by those with type 1 diabetes.

Dr. Greenfield said: “Metformin has been available in various forms for around 100 years, but its 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.”

Dr. Snaith added: “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.”