The findings by Dr. Burant and colleagues promise to raise many questions about the potential of TAK-875 in the treatment of type 2 diabetes, according to Dr. Clifford J. Bailey.
FFAR1 agonists are "different and interesting" in that they may be capable of restricted initiation of insulin secretion, and "will mainly potentiate nutrient-induced insulin secretion, which will favor enhanced prandial insulin secretion and reduce the risk of interprandial hypoglycemia," Dr. Bailey wrote in an editorial accompanying the report.
However, among the varied matters that must be addressed are durability of stimulatory effects, impact on insulin resistance, and safety, he noted (Lancet 2012 Feb. 27 [doi:10.106/S0140-6736(12)60165-2]).
"The question of durability looms large over insulin-releasing pharmacotherapies. The stimulatory effect of sulphonylureas seems to wear off and restrict long-term efficacy in many patients. ... The durability of incretin-mediated treatments awaits thorough evaluation, and now FFAR1 agonists join that waiting list," he said.
TAK-875 appeared to have no effect on insulin resistance in this study. Although this outcome was not examined in detail, the finding "revisits the therapeutic conundrum in type 2 diabetes – namely that chronically increased insulin concentrations can aggravate insulin resistance, which might offset early benefits of enhanced insulin secretion," he added.
It remains to be seen whether – along the journey to approval for this new class of treatment for type 2 diabetes – FFAR 1 agonists can "unlock the secretion-shy beta cells, provide durable efficacy, and avoid off-target safety issues," Dr. Bailey said, adding that "we travel hopefully."
Dr. Bailey is with Aston University in Birmingham, England, and Birmingham Children’s Hospital. He disclosed that he has consulted for, delivered medical education programs sponsored by, received travel reimbursement from, and/or received research grants from Bristol-Myers Squibb, AstraZeneca, Merck Sharp & Dohme, Novo Nordisk, GlaxoSmithKline, Sanofi-Aventis, and Prosidion.
