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

J Clin Endocrinol Metab. 2016 Sep;101(9):3506-15. doi: 10.1210/jc.2016-1451. Epub 2016 Aug 4.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02518945.

Publication types

  • Clinical Trial, Phase IV
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Benzhydryl Compounds / therapeutic use*
  • Biomarkers / analysis*
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Glucosides / therapeutic use*
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Liraglutide / therapeutic use*
  • Male
  • Middle Aged
  • Prognosis
  • Young Adult

Substances

  • Benzhydryl Compounds
  • Biomarkers
  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • hemoglobin A1c protein, human
  • dapagliflozin
  • Liraglutide

Associated data

  • ClinicalTrials.gov/NCT02518945