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

Abstract

OBJECTIVETo 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 METHODSTwenty-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. RESULTSTwenty 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 (22.4 6 0.8 kg [mean 6 SE] in the group with ESRD, P = 0.22; 22.9 6 1.0 kg in the control group, P = 0.03). CONCLUSIONSPlasma 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.

Review of glucagon‐like peptide‐1 receptor agonists for the treatment of type 2 diabetes mellitus in patients with chronic kidney disease and their renal effects

“…54 In a separate RCT of 24 patients with dialysisdependent ESRD, liraglutide reduced HbA1c at 12 weeks (−0.5% [−5.5 mmol/mol]) from baseline (6.7% [50 mmol/mol]), but not significantly vs placebo. 55 Nausea and vomiting occurred more frequently with liraglutide than placebo in this subpopulation. In a metaanalysis of six 26- 56 There was a trend toward increased nausea in patients with moderate or severe renal impairment.…”

“…A 26‐week RCT investigating liraglutide 1.8 mg (n = 140) vs placebo (n = 139) in patients with moderate renal impairment (eGFR 30‐59 mL/min/1.73 m 2 ) demonstrated significant HbA1c reductions with liraglutide (−1.05% vs −0.38% with placebo [−11.5 vs −4.2 mmol/mol]; P < .0001), with no effect on renal function as measured by UACR or eGFR . In a separate RCT of 24 patients with dialysis‐dependent ESRD, liraglutide reduced HbA1c at 12 weeks (−0.5% [−5.5 mmol/mol]) from baseline (6.7% [50 mmol/mol]), but not significantly vs placebo . Nausea and vomiting occurred more frequently with liraglutide than placebo in this subpopulation.…”

GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

“…The insulinotropic and glucagonostatic effects of GLP-1 described in the current study imply that GLP-1 analogues also could be an alternative in the treatment of PTDM. Short-term safety of GLP-1 treatment has recently been demonstrated in patients with type 2 diabetes treated with hemodialysis (40). In these patients, liraglutide plasma concentrations increased, so reduced treatment doses may be advisable in treatment of patients with PTDM and reduced glomerular filtration rate.…”

GIST 2.0: A scalable multi-trait metric for quantifying population representativeness of individual clinical studies

“…Due to its relatively smaller size, one institution’s EHR data is often limited in defining such EPs with adequate sample size. For example [39] requires an EP of diabetic patients undergoing dialysis but our 30,000-patient EHR data has just four such patients ( < 0.1% of its size).…”