Safety and Efficacy of Liraglutide in Patients With Type 2 Diabetes and End-Stage Renal Disease: An Investigator-Initiated, Placebo-Controlled, Double-Blind, Parallel-Group, Randomized Trial

Diabetes Care. 2016 Feb;39(2):206-13. doi: 10.2337/dc15-1025. Epub 2015 Aug 17.

Abstract

Objective: To evaluate parameters related to safety and efficacy of liraglutide in patients with type 2 diabetes and dialysis-dependent end-stage renal disease (ESRD).

Research design and methods: Twenty-four patients with type 2 diabetes and ESRD and 23 control subjects with type 2 diabetes and normal kidney function were randomly allocated to 12 weeks of double-blind liraglutide (titrated to a maximum dose of 1.8 mg) or placebo treatment (1:1) injected subcutaneously once daily as add on to ongoing antidiabetic treatment. Dose-corrected plasma trough liraglutide concentration was evaluated at the final trial visit as the primary outcome measure using a linear mixed model.

Results: Twenty patients with ESRD (1:1 for liraglutide vs. placebo) and 20 control subjects (1:1) completed the study period. Dose-corrected plasma trough liraglutide concentration at the final visit was increased by 49% (95% CI 6-109, P = 0.02) in the group with ESRD compared with the control group. Initial and temporary nausea and vomiting occurred more frequently among liraglutide-treated patients with ESRD compared with control subjects (P < 0.04). Glycemic control tended to improve during the study period in both liraglutide-treated groups as assessed by daily blood glucose measurements (P < 0.01), and dose of baseline insulin was reduced in parallel (P < 0.04). Body weight was reduced in both liraglutide-treated groups (-2.4 ± 0.8 kg [mean ± SE] in the group with ESRD, P = 0.22; -2.9 ± 1.0 kg in the control group, P = 0.03).

Conclusions: Plasma liraglutide concentrations increased during treatment in patients with type 2 diabetes and ESRD, who experienced more gastrointestinal side effects. Reduced treatment doses and prolonged titration period may be advisable.

Trial registration: ClinicalTrials.gov NCT01394341.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Blood Glucose / drug effects
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin / drug effects
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / pharmacokinetics
  • Insulin / therapeutic use
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / physiopathology*
  • Liraglutide / administration & dosage
  • Liraglutide / adverse effects*
  • Liraglutide / pharmacokinetics
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / drug therapy

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Liraglutide

Associated data

  • ClinicalTrials.gov/NCT01394341