Dapaglifozin also helped some patients lose weight; two patients developed ketones
By the University at Buffalo
University at Buffalo endocrinologists who, in recent years, found patients with Type 1 diabetes benefit from insulin plus a drug designed for Type 2 diabetes, have now found they also can benefit from dapagliflozin, another drug designed and marketed to treat Type 2 diabetes.
Today, researchers at the Jacobs School of Medicine and Biomedical Sciences at UB published a paper online ahead of print in the Journal of Clinical Endocrinology and Metabolism that reports patients with Type 1 diabetes saw improved blood glucose control with a "triple therapy" that included insulin, liraglutide and dapagliflozin.
Paresh Dandona, M.D., Ph.D., senior author on the paper, is SUNY Distinguished Professor and chief of endocrinology, diabetes and metabolism in the department of medicine in the Jacobs School of Medicine and Biomedical Sciences. He sees patients through UBMD Internal Medicine at the Diabetes and Endocrinology Center of Western New York, where the study was conducted.
Thirty people who had Type 1 diabetes participated in the randomized, placebo-controlled clinical trial. Participants were between the ages of 18 and 75, and were already taking liraglutide and insulin to manage their diabetes. Twenty participants were randomly assigned to receive 10 milligrams of dapaglifozin daily for 12 weeks, and the other 10 received a placebo during that period.
"Since liraglutide produces improvements most impressively in patients with higher body mass index and higher hemoglobin A1C, it is clear that we need other agents that act independently of insulin, since Type 1 diabetics have no beta cells that produce insulin," Dandona explained.
Hemoglobin A1C - patients' average blood glucose over a 90-day period - declined by 0.66 percent among participants who received the triple therapy, while there was no significant change in the placebo group. Fourteen of the 17 people on the triple therapy lost weight, with weight loss averaging four pounds. Patients in the placebo group did not lose weight.
Twenty-six participants completed the study. Two of the participants receiving the triple therapy developed diabetic ketoacidosis, a dangerous complication that occurs when acids and substances called ketones build up in the blood due to lack of insulin. This occurred within two days of researchers increasing the daily dapagliflozin dose to 10 milligrams from 5 milligrams. Both people were withdrawn from the study.
"Our data also show for the first time that all patients on dapagliflozin experience an increase in ketones," Dandona said. "This may predispose people to developing diabetic ketoacidosis, particularly among those who have a marked reduction in insulin from taking liraglutide together with dapagliflozin, and who have consumed too few carbohydrates. Our study sheds light on potential strategies for preventing diabetic ketoacidosis, but more research is still needed in this area."
Dandona said these data suggest insulin dose reductions should be minimized and that the higher dose of dapagliflozin should not be used in such patients.
Co-authors include: Nitesh D. Kuhadiya, Husam Ghanim, Aditya Mehta, Manisha Garg, Salman Khan, Jeanne Hejna, Barrett Torre, Antoine Makdissi, Ajay Chaudhuri and Manav Batra, all of the Jacobs School of Medicine and Biomedical Sciences at UB.
Founded in 1846, the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo is beginning a new chapter in its history with the largest medical education building under construction in the nation. The eight-story, 628,000-square-foot facility is scheduled to open in 2017. The new location puts superior medical education, clinical care and pioneering research in close proximity, anchoring Buffalo's evolving comprehensive academic health center in a vibrant downtown setting.
These new facilities will better enable the school to advance health and wellness across the life span for the people of New York and the world through research, clinical care and the education of tomorrow's leaders in health care and biomedical sciences. The school's faculty and residents provide care for the community's diverse populations through strong clinical partnerships and the school's practice plan, UBMD Physicians' Group.