Empagliflozin in posttransplantation diabetes mellitus: A prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety

Am J Transplant. 2019 Mar;19(3):907-919. doi: 10.1111/ajt.15223. Epub 2019 Jan 25.

Abstract

The safety and efficacy of sodium-glucose cotransporter 2 inhibitors in posttransplantation diabetes mellitus is unknown. We converted stable kidney transplant patients to 10 mg empagliflozin, aiming at replacing their insulin therapy (<40 IU/d). N = 14 participants (the required sample size) completed the study visits through 4 weeks and N = 8 through 12 months. Oral glucose tolerance test (OGTT)-derived 2-hour glucose (primary end point) increased from 232 ± 82 mg/dL (baseline) to 273 ± 116 mg/dL (4 weeks, P = .06) and to 251 ± 71 mg/dL (12 months, P = .41). Self-monitored blood glucose and hemoglobin A1c were also clinically inferior with empagliflozin monotherapy, such that insulin was reinstituted in 3 of 8 remaining participants. Five participants (2 of them dropouts) vs nine of 24 matched reference patients developed bacterial urinary tract infections (P = .81). In empagliflozin-treated participants, oral glucose insulin sensitivity decreased and beta-cell glucose sensitivity increased at the 4-week and 12-month OGTTs. Estimated glomerular filtration rate and bioimpedance spectroscopy-derived extracellular and total body fluid volumes decreased by 4 weeks, but recovered. All participants lost body weight. No participant developed ketoacidosis; 1 patient developed balanitis. In conclusion, although limited by sample size and therefore preliminary, these results suggest that empagliflozin can safely be used as add-on therapy, if posttransplant diabetes patients are monitored closely (NCT03113110).

Keywords: clinical research/practice; diabetes: new onset/posttransplant; endocrinology/diabetology; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; metabolism/metabolite.

MeSH terms

  • Benzhydryl Compounds / therapeutic use*
  • Blood Glucose / metabolism*
  • Body Composition
  • Body Fluids / metabolism*
  • Diabetes Mellitus, Type 2 / therapy*
  • Early Medical Intervention
  • Female
  • Follow-Up Studies
  • Glucosides / therapeutic use*
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Rejection / metabolism
  • Graft Survival
  • Humans
  • Insulin / metabolism
  • Islets of Langerhans Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Patient Safety
  • Pilot Projects
  • Postoperative Complications / drug therapy*
  • Postoperative Complications / etiology
  • Postoperative Complications / metabolism
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Insulin
  • Sodium-Glucose Transporter 2 Inhibitors
  • empagliflozin

Associated data

  • ClinicalTrials.gov/NCT03113110