NEW ORLEANS – The second trial involving a sub-dermal matchstick-size osmotic mini-pump that releases exenatide over 6 months in people who have poorly controlled type 2 diabetes achieved superior blood glucose levels and weight loss after a year, compared with sitagliptin alone, Dr. Julio Rosenstock reported at the annual scientific sessions of the American Diabetes Association.
Dr. Rosenstock, director of the Dallas Diabetes and Endocrine Center, reported on the findings of the study, known as FREEDOM-2. The study randomized 535 adults with poorly controlled type 2 diabetes to either the mini-pump, known as the ITCA 650, that releases 60 μg of exenatide a day, or 100 mg of daily sitagliptin. This is a follow-on trial to FREEDOM-1 that compared the ICTA 650 mini-pump to twice-daily exenatide in people with type 2 diabetes who were taking metformin (Diabetes Care. 2013 Sep;36:2559-65). All participants in FREEDOM-2 had been on metformin greater than or equal to 1,500 mg daily and had HbA1c greater than or equal to 7.5%.
“The continuous subcutaneous delivery of exenatide with ICTA 650 is a novel approach to improve glycemic control, ensuring adherence and consistent delivery of therapy for 6-12 months for people with type 2 diabetes,” Dr. Rosenstock said. The ICTA recipients first received a dose of 20 μg of exenatide daily for the first 12 weeks, then had that increased to 60 μg for the remainder of the study.
After 1 year, average reduction in HbA1c was 1.5% with ITCA 650 vs. 0.8% with sitagliptin, Dr. Rosenstock said. Sixty-one percent of those in the ITCA 650 group achieved greater than 0.5% reductions in HbA1c and more than 2 kg loss in body weight after a year, compared with 28% of the sitagliptin group.
Overall, the patients who receive the ITCA 650 achieved an average body weight reduction of 4 kg vs. 1.3 kg for the sitagliptin patients. Again, 61% of the ITCA patients achieved target HbA1c of less than 7% vs. 42% of the sitagliptin group. Rescue therapy was required in 15% with ITCA 650 and 35% with sitagliptin, and minor hypoglycemia occurred in 4.2% with ITCA 650 vs. 1.9% with sitagliptin.
The ICTA 650 group did have a higher incidence of adverse events, Dr. Rosenstock said, 82% vs. 74%. These included side effects at the application site like hematoma, bleeding, infection, or pain, as well as gastrointestinal (GI) problems such as nausea and vomiting. “The GI adverse events were similar to what we have seen with other GLP-1 receptor agonists,” Dr. Rosenstock said. “The incidence of nausea spiked at the initial insertion and then when we increased the dose from 20 μg to 60 μg, but the second time the ICTA 650 was replaced for 60 μg dosing, the nausea rates did not spike.” The ICTA 650 group had a discontinuation rate of 1%.
Each mini-pump inserted in the FREEDOM-2 trial had a duration of 6 months, but Dr. Rosenstock said the goal is to achieve extended-release dosing with a single mini-pump for 2 years.
Dr. Rosenstock disclosed he serves on the advisory panels of Boehringer Ingelheim Pharmaceuticals, Daiichi-Sankyo Co., Eli Lilly and Company, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, MannKind Corporation, Merck & Co., Novartis, Novo Nordisk, Sanofi U.S., and Takeda Pharmaceutical Company; and that he has received research support from Amylin Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, MannKind Corporation, Merck & Co., Novartis, Novo Nordisk, Pfizer, Roche Pharmaceuticals, Sanofi U.S. and Takeda.