SGLT2 inhibitor empagliflozin can be used to treat insulin resistance in the brain, finds study

Overweight or obesity, unwanted distribution of body fat and the development of type 2 diabetes are often associated with a decreased effect of the hormone insulin in many organs, including the brain (insulin resistance).

So far there is no treatment to restore insulin sensitivity in the brain, which plays a key role in controlling metabolism. Researchers of the German Center for Diabetes Research (DZD), the Departments of Internal Medicine IV (Director: Prof. Andreas Birkenfeld) and Clinical Chemistry and Pathochemistry (Director: Prof. Andreas Peter) of the University Hospital Tübingen and the Research Institute for Diabetes and Metabolic Diseases (IDM) in Helmholtz Munich have now shown For the first time, the SGLT2 inhibitor empagliflozin can be used to treat insulin resistance in the brain – with positive effects on whole-body metabolism. This study has now been published in Diabetes care.

The brain has a critical influence on our food behavior and thus on body weight and metabolism. If the brain reacts sensitively to insulin, we eat less, less belly fat is stored, and the body’s sensitivity to insulin improves. However, in people with obesity or type 2 diabetes, the hormone in the brain is no longer effective.

This insulin resistance leads to a metabolic disorder. So far, insulin resistance in the brain cannot be treated with medication. The researchers investigated whether a diabetes drug from the group of SGLT2 inhibitors could also reverse insulin resistance in the brain. SGLT2 inhibitors reduce elevated blood glucose levels in diabetes by enhancing urinary glucose excretion and have a beneficial effect on the heart, circulatory system, and kidneys. For this purpose, the effect of the SGLT2 inhibitor empagliflozin on brain insulin sensitivity in study participants with initial stage of diabetes (prediabetes) was investigated.

In a prospective, randomized, double-blind study, 40 subjects with prediabetes (age: 60 ± 9 years; BMI: 31.5 ± 3.8 kg/m2) received empagliflozin or placebo for eight weeks. The researchers used functional magnetic resonance imaging (fMRI) to determine insulin sensitivity in the brain before and after treatment. For this purpose, individuals were administered insulin by nasal spray. When the hormone is absorbed through the nose, it reaches the brain directly. In addition, whole-body MRI was used to determine fat distribution.

An SGLT2 inhibitor increases insulin sensitivity in the brain

“While taking placebo had no effect on insulin action in the brain, empagliflozin treatment significantly improved the hormone’s effect on brain activity,” said lead researcher Dr. Stephanie Coleman, summarizing the results of the study. Administration of empagliflozin also improved fasting glucose levels and reduced liver fat content. Although the SGLT2 inhibitor did not reduce weight, it did reduce body fat content.

First pharmacological approach to reverse insulin resistance in the brain

Our studies confirm insulin resistance in the brain in people with prediabetes. Treatment with empagliflozin was able to restore insulin sensitivity. These results position SGLT2 inhibitors as the first potential pharmacological approach to treat insulin resistance in the brain. Increased insulin sensitivity also contributes to improving the body’s metabolism. “

Martin Heaney, another study author and professor, University Hospital Tübingen

As a next step, the researchers plan to investigate whether the improved action of insulin in the brain is also involved in the beneficial effects of SGLT2 inhibitors on the heart and kidneys.

source:

German Diabetes Research Center DZD

Journal reference:

Coleman, S.; and others. (2021) Empagliflozin improves insulin sensitivity in the hypothalamus in humans with diabetes: a randomized, double-blind, placebo-controlled, phase II trial. Diabetes care. doi.org/10.2337/dc21-1136.

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