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TAK-875: A novel drug for Type 2 diabetes

Kathleen Blanchard's picture
A new drug for diabetes lowers blood sugar levels without risk of hypoglycemia.

Researchers have developed a novel way to control Type 2 diabetes with the oral drug TAK-875. The drug targets cells in the pancreas that stimulate the production of insulin, without the risk of hypoglycemia. Compared to the popular diabetes drug, glimepiride, patients studied had less risk of developing low blood sugar. If levels are normal, TAK-875 has no effect.

Results of a Phase 2 clinical trial, published in the journal Lancet, found the drug worked well to lower HbA1C levels in patients with Type 2 diabetes who failed to keep the disease under control with diet, exercise or the diabetes drug metformin.

After 12-weeks, 33 to 48 percent of patients given TAK-875, compared to placebo, were able to get their HbA1C levels below the recommended 7%. Glimiperide had a similar effect in the trial

Charles Burant, M.D., Ph.D., professor of internal medicine at the University of Michigan Health System, and colleagues included 496 patients with Type 2 diabetes in the study; 303 of the patients received 1 of 5 doses of the TAK-875, 61 were given a placebo, and 62 were given glimepiride.

Burant is an unpaid consultant and advisor to Takeda Global Research and Development which discovered TAK-875.

Twice as many patients achieved target HbA1C levels at a dose of 25mg or higher.

Compared to placebo, rates of hypoglycemia were similar. Compared to glimiperide, low blood sugar levels were significantly fewer with all doses of TAK-875.

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The drug works by targeting fatty acid receptors when glucose levels rise in the bloodstream after eating a meal.

Type 2 diabetes is a major health issue that stems from inability of the pancreas to produce enough insulin, which is a hormone that regulates glucose in the body.

Estimates are that 150 million people are living with the disease; 90% have Type 2 diabetes.

Free fatty acid receptor (FFAR) 1, also known as G protein-coupled receptor 40, or GPR40, is crucial for stimulating insulin release from β-cells in the pancreas. Drugs like glimepiride and TAK-875 stimulate the body to release more insulin by activating the FFAR1 receptor.

The study authors said in a media release, “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.”

TAK-875 works like other Type 2 diabetes drugs, but is novel because it won’t lower blood sugars to dangerous levels. It only acts when glucose levels are high.

The Lancet
“TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial”
Prof Charles F Burant, et al.
February 27, 2012

Image credit: Morguefile