Triple therapy for type 1 diabetes improves glycemic control and weight loss

Adding dapagliflozin to the combination therapy of insulin and liraglutide in patients with type 1 diabetes significantly improved blood glucose control and lowered weight, according to a study published August 4, 2016 in the Journal of Clinical Endocrinology & Metabolism.

However, the three-drug combination also increased ketosis in patients, the researchers learned.

“Our research found a triple therapy (insulin, liraglutide, and dapagliflozin) approach led to impressive improvements in blood glucose control as well as weight loss. This strategy advances our previous work showing improvements in blood glucose management with the use of liraglutide in combination with insulin,” said the study’s senior author, Paresh Dandona, MD, PhD, Chief of Endocrinology, Diabetes and Metabolism at the State University of New York at Buffalo, in Buffalo, NY.

Currently, most patients with type 1 diabetes don’t have their HbA_1c levels under the 7% target goal, so new approaches are needed, the researchers wrote in their article.

“A majority of patients who have type 1 diabetes do not have their blood glucose levels sufficiently controlled and monitored, and then they are left vulnerable to more complications of the disease,” Dr. Dandona said.

For this randomized clinical trial, the researchers recruited 30 type 1 diabetes patients (ages 18 to 75) who had been on insulin and liraglutide therapy for at least 6 months. The investigators randomly assigned 20 patients to add 10 mg of dapaglifozin daily for 12 weeks, while the other 10 patients added a placebo to their regimen.

All patients wore continuous glucose monitors (CGMs) during the course of the study. From these monitors, the researchers downloaded weekly reports of the patients’ average weekly glucose, fasting glucose, variability of blood glucose concentrations, and percentage of time spent in different glycemic thresholds. The researchers also periodically measured patients’ weight during the study.

At the end of 12 weeks, triple therapy had reduced HbA1c by 0.66% in treated patients, while patients on placebo had no significant change. Most patients on triple therapy also lost weight, by an average 1.9 kg.

“The combination of a reduction in glycemia and body weight implies a reversal in two cardinal features of the metabolic syndrome and hence should result in the [reduction of] overall cardiovascular risk in these patients in addition to the risk for microvascular complications,” the researchers concluded.

Not all patients were able to complete the study, however. The researchers withdrew two patients who developed diabetic ketoacidosis while on triple therapy.

“Our data show for the first time that all patients on dapagliflozin experience an increase in ketones,” Dr. 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.”

He added, “Our study sheds light on potential strategies for preventing diabetic ketoacidosis, but more research is still needed in this area.”