TAK-875 controls blood sugar, reduces hypoglycemia risk

An experimental diabetes drug, TAK-875, demonstrated its ability to improve blood-sugar control with a low risk of hypoglycemia, according to phase 2 study results published online February 27 in The Lancet.

“The expected increase in the number of cases of type 2 diabetes during the next few decades, and the recognition that existing treatments either have insufficient effect on a disease that is progressive in nature or are associated with side effects that might restrict their use, emphasizes the need for additional therapeutic agents,” said Charles Burant, MD, PhD, professor of internal medicine at the University of Michigan Health System, and colleagues.

The researchers designed this randomized, double-blind, placebo- and active-comparator-controlled trial to assess whether selective pharmacological activation of free fatty acid receptor 1 (FFAR1) by TAK-875 would improve glycemic control without hypoglycemia risk in patients with type 2 diabetes who had not responded to diet, exercise, or metformin treatment.

Between November 17, 2009, and September 29, 2010, the researchers randomly assigned 426 patients at 95 sites in the United States, Mexico, and Guatemala to 1 of 5 doses of TAK-875 (n=303), placebo (n=61), or glimepiride (n=62) for 12 weeks. The primary outcome was change in glycosylated hemoglobin (HbA_1c) from the start of the study.

Results showed that TAK-875 was well-tolerated and that, at 12 weeks, all doses of TAK-875 resulted in significant reductions in HbA_1c from baseline (ranging from −1.12% with 50 mg to −0.65% with 6.25 mg) compared with placebo (−0.13%). A similar reduction was noted with glimepiride (−1.05%); however, significantly higher rates of treatment-emergent hypoglycemic events were reported in the glimepiride group (19% [n=12] vs 2% [n=7, all TAK-875 groups], 3% [n=2, placebo]).

The investigators noted that the results were promising but acknowledged their small sample size.

“As with all novel treatments, additional studies of longer duration to assess true efficacy, durability of clinical efficacy, and safety of TAK-875 will be needed to establish the appropriate placement of FFAR1 agonists in the treatment framework for type 2 diabetes,” they wrote.