Approved Research

Impact of metformin treatment on brain structure and function

Lay summary

Metformin, a medication for diabetes, has been shown in mouse studies to have a wide range of effects on the brain. Some of these effects were clearly beneficial, but some also raise concerns. Unfortunately, similar studies looking at what metformin does to the brain in humans are lacking. Given the large number of people, both children and adults, taking metformin for a variety of conditions and the mixed results from studies in mice, it is critically important to find out if metformin affects the human brain and how it does so.

In the past, it has been very difficult to determine whether a drug affects the brain's structure or function. The limitations lay in poor quality/availability of brain images and the small numbers of participants. The UK Biobank prospective study provides a unique resource that gives us the opportunity to look at metformin's effect on the brain taking advantage of advanced brain imaging technologies and the incredibly large number of participants taking metformin (nearly 16000).

To assess whether metformin affects the brain we will analyse brain images of people taking metformin and compare them to brain images of those who are not. From these brain pictures we will be able to say whether brain's structure and/or function is changed by metformin treatment. We will try to identify people whose brain seems to respond positively to metformin and those who may have a negative response. We will further try to determine what causes differences in people's response to metformin, considering things such as their age, sex, genetics and lifestyle.

Even though metformin has been shown to be relatively safe and well tolerated by patients with diabetes and prediabetes, some side effects have been identified. These may include blood and kidney problems, and upset stomach and metallic taste. Little is known about the brain side effects of metformin, which is what we will address in our proposal.