The Lancet published results of a phase 2, randomized trial of TAK-875, a new treatment for type 2 diabetes online, which demonstrates that it is comparative to glimepiride in its ability to improve blood sugar control, but the risk of hypoglycemia, i.e. creating dangerous drops in blood sugar levels is substantially lower.
Of the 150 million diabetics currently living in the U.S., about 90% suffer from diabetes type 2, the most common form of diabetes, which is primarily caused by a lack of response to insulin that leads to high blood sugar levels and a variety of chronic conditions.
Free fatty acid receptor 1, also known as G protein-coupled receptor 40, or GPR40, has a vital impact on the stimulation and regulation of insulin production and works by boosting the release of insulin from pancreatic β-cells when glucose and fatty acids elevate in the blood, for instance after a meal, when blood glucose levels decrease. Drugs activating the FFAR1 receptor can potentially assist diabetics in releasing more insulin and improving control of blood glucose levels.
TAK-875 is a novel oral medication that has been developed to improve the secretion of insulin in a glucose-dependant manner, meaning it has no impact on insulin secretion when glucose levels are normal, and therefore has the potential to improve the control of blood sugar levels without the risk of hypoglycemia.
Charles Burant, M.D., Ph.D., professor of internal medicine at the University of Michigan Health System, and his team randomly assigned 426 patients with type 2 diabetes to one of five doses of either TAK-875, a placebo, or glimepiride, a standard diabetes treatment. All of the participants had failed to achieve adequate glucose control through diet, exercise or metformin treatment. The primary outcome was defined as a change in hemogloblin A1c from the start of the study.
They noted at 12 weeks that in comparison with placebo, all doses of TAK-875 achieved a substantial drop in HbA1c levels that was comparable to the reduction achieved in patients who received glimepiride.
Around twice as many patients, i.e. 33 to 48% reached the American Diabetics Association target of HbA1c less than 7% within 12 weeks after receiving a TAK-875 dose of 25 mg or higher, compared with 19 % in the placebo group and a similar numbers of participants (40%) in the glimepiride group.
It was observed that TAK-875 was generally well tolerated with a substantially lower rate of hypoglycemia incidences (2%) for all doses of TAK-875 compared with glimepiride (19%), and similar rates of 2% with placebo.
The total rate of incidence of treatment-related side effects was similar for the TAK-875 group (49%) and the placebo group (48%), whilst the glimepiride group had an incident rate of 61% due to the higher risk of hypoglycemia.
The researchers declare:
“In view of the frequent hypoglycemia after treatment with sulfonylureas, the low-risk of hypoglycemia after treatment with TAK-875 suggests that there may be therapeutic advantage of targeting FFAR1 in treating people with type 2 diabetes.”
In a concluding statement they say:
“We are truly excited about the potential of TAK-875 and are eager to conduct larger trials to find out how well this drug works, how safe it is and what its place is in the treatment of diabetes. TAK-875 significantly improved glycemic control in patients with type 2 diabetes with minimum risk of hypoglycemia. The results show that activation of FFAR1 is a viable therapeutic target for treatment of type 2 diabetes.”
Written by Petra Rattue