Takeda Pharmaceutical Co. has successfully come up with a diabetes drug that lowered blood sugar as much as an older generic medicine with fewer side effects.
In a trial of 426 patients with Type 2 diabetes, TAK-875 reduced blood sugar below a pre-determined level in as much as 48 percent of those receiving it after 12 weeks, compared with 40 percent of those who took glimepiride, the older drug, according to findings published online by The Lancet medical journal. The research was presented in June at the American Diabetes Association’s annual meeting in San Diego.
TAK-875 is now being tested in its third and final stage of patient studies usually required for regulatory approval. The Osaka, Japan-based company seeks products to replace sales of Actos, the world’s best-selling diabetes treatment.
About 90 percent of the 285 million people worldwide with diabetes have Type 2. Often tied to obesity, type 2 diabetes involves a gradual decline in how insulin responds to changes in blood sugar (glucose).
The pill belongs to a new class of treatments called GPR40 agonists, which activate a receptor that stimulates and regulates insulin production. New treatments are needed because of “the expected increase in the number of cases of Type 2 diabetes during the next few decades” and because some current drugs have “insufficient effect,” the researchers, led by Charles Burant at the University of Michigan Medical School, wrote in the study.
Free fatty acid receptor 1 (FFA1), also known as G protein-coupled receptor 40 (GPR40), plays a vital role in stimulating and regulating the production of insulin. It works by boosting the release of insulin from pancreatic β-cells when glucose and fatty acids rise in the blood, such as after a meal. The release of insulin results in a fall in blood glucose levels. Drugs that activate the FFAR1 receptor have the potential to help diabetics release more insulin and improve control of blood glucose levels.
About 2 percent of those receiving TAK-875 in the trial developed hypoglycemia, a complication in which blood sugar is lowered too much, compared with 19 percent of those receiving glimepiride, the researchers wrote. About half of the TAK-875 group experienced an adverse side effect of any kind, compared with 61 percent of those in the glimepiride group.
Authors write that they are “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.”
In a journal commentary, Clifford Bailey of Aston University in Birmingham, England, cautioned that, “on the journey to approval of a new class of treatment for type 2 diabetes, many questions will be asked of [drugs such as TAK-875],” including questions of how long they might remain effective, as well as safety issues.
Dr. Loren Wissner Greene is clinical associate professor of endocrinology at NYU Langone Medical Center in New York City. She noted that glitazones - a separate class of newer drugs such as Rezulin, Avandia and Actos that also target insulin resistance - have all shown initial promise in clinical trials before worrisome side effects began to surface in users. Avandia was recently withdrawn from the U.S. market due to heart risks.
As for TAK-875, it targets a separate mechanism “but again, until more is known about short-term and long-term cardiovascular effects, we need to proceed with moderated enthusiasm for each new drug and drug mechanism,” Wissner Greene said.
Dr. Minisha Sood, endocrinologist at Lenox Hill Hospital in New York City stressed that, “given the rising global incidence of type 2 diabetes, the medical community is eagerly awaiting the development of novel agents to add to our existing armamentarium of anti-diabetic agents.”
She said that, “though this study includes a small sample size followed for a short period of time, the results are promising in that TAK-875 appears to be effective for glycemic [blood sugar] control without significant risk for hypoglycemia or weight gain.” However, like Wissner-Greene, Sood said that “further investigation is warranted, especially including [heart disease] patients.”
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