Type 1 diabetes is an autoimmune disease in which the immune system destroys the insulin-producing cells of the pancreas. As a result, blood sugar builds in the bloodstream and cells cannot get the energy they need to function. Long-term increases in blood sugar levels lead to complications, which include blindness, kidney failure, nerve damage, heart attack and stroke.
A combination of three medications-dapagliflozin, liraglutide and insulin-helped people with Type 1 diabetes improve blood sugar control and lose weight, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.
More than 29 million Americans have diabetes, but only a fraction of them have Type 1 diabetes. Out of every 1,000 American adults, between one and five adults has Type 1 diabetes, according to the Endocrine Society's Endocrine Facts and Figures Report. People who have Type 1 diabetes can experience serious health problems such as heart attacks and strokes, kidney problems and vision problems.
Thirty people who had Type 1 diabetes participated in the randomized, placebo-controlled clinical trial. The phase IV study's participants were between the ages of 18 and 75, and they 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.
During the study, the participants used continuous glucose monitors (CGMs) to track their blood glucose levels. The researchers downloaded weekly reports from the CGMs to monitor the participants' ability to manage their average blood glucose levels from the past three months, a measurement called HbA1c. The researchers also tracked the participants' weight during the study.
HbA1c declined by 0.66% among participants who received the triple therapy, while there was no significant change in the placebo group. Participants who received the triple therapy lost 1.9 kilograms, on average, and 14 of the 17 people on the triple therapy lost weight. In comparison, the placebo group's body weight remained unchanged.
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. On the basis of the data, the dose reduction of insulin should be minimized and the higher dose of dapagliflozin should not be used in such patients. Our study sheds light on potential strategies for preventing diabetic ketoacidosis, but more research is still needed in this area."
The study, "Dapagliflozin as Additional Treatment to Liraglutide and Insulin in Patients with Type 1 Diabetes," will be published online at http://press.endocrine.org/doi/10.1210/jc.2016-1451, ahead of print.
Other authors of the study include: Nitesh D. Kuhadiya, Husam Ghanim, Aditya Mehta, Manisha Garg, Salman Khan, Jeanne Hejna, Barrett Torre, Antoine Makdissi, Ajay Chaudhuri and Manav Batra of the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo in Buffalo, NY.
The research was funded by the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo.
Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world's oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.