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.
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).


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.
Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark thomas.idorn@regionh.dk.
Thomas
T
Idorn
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Filip K
FK
Knop
Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Morten B
MB
Jørgensen
Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Tonny
T
Jensen
Department of Internal Medicine, Hillerød Hospital, University of Copenhagen, Hillerød, Denmark.
Marsela
M
Resuli
Department of Internal Medicine, Hillerød Hospital, University of Copenhagen, Hillerød, Denmark.
Pernille M
PM
Hansen
Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
Karl B
KB
Christensen
The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jens J
JJ
Holst
Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Mads
M
Hornum
Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Bo
B
Feldt-Rasmussen
D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D007328:Insulin / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*; D000069450:Liraglutide / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide