Dapagliflozin as Additional Treatment to Liraglutide and Insulin in Patients With Type 1 Diabetes.

CONTEXT It is imperative that novel approaches to treatment of type 1 diabetes (T1D) are devised. OBJECTIVE The objective of the study was to investigate whether addition of dapagliflozin to insulin and liraglutide results in a significant reduction in glycemia and body weight. DESIGN This was a randomized clinical trial. SETTING The study was conducted at a single academic medical center. PARTICIPANTS Participants included T1D patients on liraglutide therapy for at least last 6 months. INTERVENTION Thirty T1D patients were randomized (in 2:1 ratio) to receive either dapagliflozin 10 mg or placebo daily for 12 weeks. MAIN OUTCOME MEASURE Change in mean glycated hemoglobin after 12 weeks of dapagliflozin when compared with placebo was measured. RESULTS In the dapagliflozin group, glycated hemoglobin fell by 0.66% ± 0.08% from 7.8% ± 0.21% (P < .01 vs placebo), whereas it did not change significantly in the placebo group from 7.40% ± 0.20% to 7.30% ± 0.20%. The body weight fell by1.9 ± 0.54kg (P < .05 vs placebo). There was no additional hypoglycemia (blood glucose < 3.88 mmol/L; P = .52 vs placebo). In the dapagliflozin group, there were significant increases in the plasma concentrations of glucagon by 35% ± 13% (P < .05), hormone-sensitive lipase by 29% ± 11% (P < .05), free fatty acids by 74% ± 32% (P < .05), acetoacetate by 67% ± 34% (P < .05), and β-hydroxybutyrate by 254% ± 81% (P < .05). Urinary ketone levels also increased significantly (P < .05). None of these changes was observed in the placebo group. Two patients in the dapagliflozin group developed diabetic ketoacidosis. CONCLUSIONS Addition of dapagliflozin to insulin and liraglutide in patients with T1D results in a significant improvement in glycemia and weight loss while increasing ketosis. If it is decided to use this approach, then it must be used only by a knowledgeable patient along with an endocrinologist who is well versed with it.