HealthDay News — An investigative drug known as TAK-875 increased insulin secretion without raising hypoglycemia risk in patients with type 2 diabetes who did not respond to diet modification or treatment with metformin, results of a phase 2 study show.

Patients who took 50 mg/day of TAK-875, an oral free fatty acid receptor 1 (FFAR1) agonist, had a mean reduction in glycated hemoglobin (HbA1c) of −1.12% at week 12, compared with −1.05% in patients on 4 mg of the sulfonylurea glimepiride daily and −0.13% in those on placebo, Charles F. Burant, MD, from the University of Michigan in Ann Arbor, and colleagues report in Lancet.

During the 12-week study period, treatment-emergent hypoglycemic event rates were similar among patients randomly assigned to TAK-875 (N=303; 2%) and those assigned to placebo (N=61; 3%), but were significantly higher among patients in the glimepiride group (N=62; 19%). 

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Similarly, adverse event rates were comparable in the TAK-875 and placebo groups (49% and 48%, respectively), but were significantly higher in the glimepiride group (61%). Three patients discontinued TAK-875 due to renal failure and myocardial infarction, and two patients discontinued glimepiride because of angina and hyperglycemia. There were no differences in reported BP, cholesterol or liver enzymes.

“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,” the researchers wrote.

TAK-875 works by activating FFAR1, a cell-surface receptor expressed in pancreatic beta cells. When activated, FFAR1 raises insulin secretion, but only when glucose levels are elevated.

Participants assigned to any dose of the investigational drug experienced significant HbA1c reductions varying in range from 6.2 mg per day to 200 mg per day, with the changes evident about one month after therapy initiation. The percentage of patients who achieved the HbA1c target established by the American Diabetes Association of less than 7% ranged from 33% to 48% in the 25 mg to 200 mg dose groups.

Study limitations included small sample size and short duration. All researchers disclosed ties to Takeda Global Research and Development, which funded the study and manufactures TAK-875.

Burant CF et al. Lancet. 2012;doi:10.1016/S0140-6736(11)61879-5.