New drug combination may help improve blood sugar and weight loss in Diabetics

Given the synergistic effect of the drugs in pancreatic beta cells, the team tested whether their findings would hold true in obese mice, fed a high-fat diet. Shilpak Bele, the graduate student under Dr. Mitra's direction, and other team members found that mice treated with the combination of GLP-1 agonist and MS-275 had a much lower fasting glucose level than control mice that were sustained with repeat dosing. Where a high-fat diet increased fasting blood sugar in the untreated mice, the mice on the combination treatment remained in control.

Given these effects on blood sugar, the team explored whether the combination treatment also minimised weight gain. Mice given the combination treatment had a significant and sustained reduction in their food intake, which resulted in weight loss. When treatment was interrupted, the mice regained weight. Once the treatment was resumed, only the mice receiving the combination treatment showed significant weight loss again.

"GLP-1 drugs have emerged in the last decade as unique medicines that provide substantial improvements in glycemic control and body weight; however, they seldom achieve full metabolic recovery or help treat associated comorbidities such as body weight," Dr. Mitra explains. "Our results suggest that the class 1 HDAC 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/HDAC inhibitors for the long-term management of diabetes and obesity in humans.