A group of researchers at Dr Reddy’s Institute of Life Sciences, India, have found that an experimental cancer drug called MS-275, when used along with a class of diabetes drugs called Glucagon-like peptide 1 agonists or GLP-1 analogues help control blood glucose levels and weight loss in mice models of diabetes associated with obesity.
The findings of the study published in the journal eLife suggest that both these drugs may be used in combination for the treatment of obesity and diabetes, two conditions that have reached epidemic proportions in the world.
As per the World Health Organisation, about one billion people in the world are overweight right now and about 300 million of them are obese. More than 422 million people in the world have diabetes. The WHO and associated countries have targeted to stop the rise in both these conditions by 2025.
GLP-1 analogues and MS-275
GLP-1 analogues, also called incretin mimics, are a rather new class of injectable drugs that are given to patients with type 2 diabetes who can’t control their blood glucose levels with oral medications.
These drugs mimic the action of incretins, a group of hormones that help control blood glucose levels after meals by stimulating insulin secretion from the pancreas. Our body releases incretins during uptake of nutrients from food. The pancreas is a gland located inside the abdominal cavity. Beta-cells in the pancreas are responsible for producing insulin.
Apart from promoting insulin release, GLP-1 analogues also prevent the release of another hormone called glucagon, which otherwise promotes the breakdown of stored sugars in glucose and its release in the bloodstream.
Additionally, these drugs prolong glucose absorption in the gut.
MS-275, on the other hand, is a class 1 histone deacetylase inhibitor drug that has antiproliferative action, meaning it suppresses tumour growth.
The combination therapy
For the study, the research team assessed several drugs to see if they improved the effects of GLP-1 analogues on incretin receptors. The activity of the drugs was measured with the help of another molecule called cAMP. cAMP is a messenger molecule involved in various biological processes. The levels increase gradually with the activation of incretin receptors.
About four different molecules were found to be effective in enhancing the effects of GLP-1 analogues. However, MS-275 was the best, showing a 3.5 times increment.
Next, the researchers tested the effects of the drug combination on obese mice. They found that the treatment was effective in controlling fasting blood glucose levels when given regularly to the animals. The mice also had a significant reduction in their food intake and gradually lost weight.
The test mice started to gain weight again once the treatment was stopped and when the researchers restarted the drug treatment, mice who received both the drugs again lost weight.
Explaining the scope of the study, Dr Prasenjit Mitra, project head, said in a news release, “Our results suggest that the class 1 HDAC (Histone deacetylase) inhibitor MS-275 can significantly enhance the action of GLP-1 drugs, more effectively normalising blood glucose and reducing weight gain. This lays the foundation for clinical studies of combinations of GLP-1 and HDAC inhibitors for the long-term management of diabetes and obesity in humans.”
For more information, read our article on Diabetes.
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