NEW ORLEANS – The addition of dapagliflozin to insulin and liraglutide in patients with type 1 diabetes resulted in a significant improvement in glycemia, results from a single-center randomized trial showed.
“Because liraglutide suppresses glucagon and lowers free fatty acids while SGLT-2 inhibitors increase glucagon and risk of diabetic ketoacidosis, it’s possible that the combination of the two agents may neutralize the diabetic ketoacidosis risk,” Paresh Dandona, MD, said at the annual scientific sessions of the American Diabetes Association.
In a recent study Dr. Dandona, chief of endocrinology at the University of Buffalo (N.Y.), and his associates showed that the addition of liraglutide to insulin significantly improved glycemic control in patients with type 1 diabetes (Diabetes Care 2016 Jun; 39:1027-35). The purpose of the current study was to investigate whether the addition of dapagliflozin, a sodium-glucose cotransporter–2 inhibitor, to the combination of insulin and liraglutide would further improve glycemic control.
A total of 30 type 1 diabetes patients on insulin and liraglutide therapy for a minimum of 6 months were randomized to receive either dapagliflozin 10 mg or placebo daily for 12 weeks. Dapagliflozin was initiated at 5 mg daily for 1 week and increased to 10 mg daily thereafter. All patients had type 1 diabetes for at least 1 year, were on insulin therapy, had no detectable C-peptide in plasma, and were on 1.8 mg of liraglutide for 7 months. These patients were evaluated every week for the first and last 2 weeks and then every 2 weeks for 12 weeks. Blood and 24-hour urine samples were collected before and after intervention.
At baseline, the mean age of patients was 54 years and both groups were similar in terms of mean hemoglobin A1c, glucose levels, and insulin dosages. After 12 weeks, the mean HbA1c did not change in the placebo group, but it dropped significantly in the triple-therapy group, by .66% (P less than .01). In addition, the average weekly glucose concentration fell in the triple-therapy group by 13 mg/dL (P = .35) and there was a reduction in standard deviations of glycemic excursions. The triple-therapy group also experienced a small reduction in the total insulin dose, compared with the placebo group (–3.5 vs. –.4 units, respectively; P = .29)
Dr. Dandona went on to note that the episodes of hypoglycemia did not increase after triple therapy but body weight fell by 1.9 kg after 12 weeks, while there was no real change in the placebo arm. Two patients had to withdraw from the study because they developed diabetic ketoacidosis within a day after increasing the dose of dapagliflozin to 10 mg. “One of these patients had euglycemic DKA with blood glucose concentrations of less than 160 mg/dL, while the other had marked hyperglycemia with unchanged insulin dose at 26 units,” Dr. Dandona said. “This patient had experienced a marked reduction in insulin dose during the time she was on liraglutide prior to starting on dapagliflozin.”
Dr. Dandona disclosed that he has received research support from AstraZeneca and Novo Nordisk.