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

TY - JOUR

T1 - Safety and Efficacy of Liraglutide in Patients With Type 2 Diabetes and End-Stage Renal Disease

T2 - An Investigator-Initiated, Placebo-Controlled, Double-Blinded, Parallel Group, Randomized Trial

AU - Idorn, Thomas

AU - Knop, Filip K

AU - Jørgensen, Morten B

AU - Jensen, Tonny

AU - Resuli, Marsela

AU - Hansen, Pernille M

AU - Christensen, Karl B

AU - Holst, Jens J

AU - Hornum, Mads

AU - Feldt-Rasmussen, Bo

N1 - © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

PY - 2016/2

Y1 - 2016/2

N2 - 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 (22.4±0.8 kg [mean±SE] in the group with ESRD, P = 0.22;22.9±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.

AB - 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 (22.4±0.8 kg [mean±SE] in the group with ESRD, P = 0.22;22.9±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.

U2 - 10.2337/dc15-1025

DO - 10.2337/dc15-1025

M3 - Journal article

C2 - 26283739

SN - 0149-5992

VL - 39

SP - 206

EP - 213

JO - Diabetes Care

JF - Diabetes Care

IS - 2

ER -