The Glycemic Effect of Liraglutide Evaluated by Continuous Glucose Monitoring in Persons with Type 2 Diabetes Receiving Dialysis.

AIMS: The aim of this study was to evaluate the effect of liraglutide treatment on glucose variability and the risk of hypoglycemia by continuous glucose monitoring (CGM) in persons with type 2 diabetes (T2D) and dialysis-dependent end-stage renal disease (ESRD). MATERIALS AND METHODS: We assessed CGM data from a previous trial where 24 persons with T2D and dialysis-dependent ESRD were allocated (1:1) to 12 weeks of double-blinded treatment with liraglutide (titrated to maximum tolerable dose up to 1.8 mg) or placebo as an add-on to preexisting antidiabetic treatment. CGM (Ipro2®; Medtronic) was performed for up to 7 days at baseline and at weeks 2, 6, and 10. A linear mixed model was used to compare the 2 study arms. RESULTS: A CGM was worn at baseline by 12 persons in the liraglutide group and 10 in the placebo group (7 and 9 completed week 10, respectively). Glycated hemoglobin A1c (p = 0.81) and glucose variability was similar between the groups (standard deviation, p = 0.33; coefficient of variation, p = 0.16). Comparing baseline and week 10, the number of hypoglycemic events (glucose values between <3.9 and 3.0 mmol/L) increased in the liraglutide group compared with the placebo group (p = 0.02). The occurrence of hypoglycemic events below 3.0 mmol/L was similar between the groups (p = 0.36). CONCLUSIONS: In the present cohort of persons with T2D and dialysis-dependent ESRD, liraglutide treatment increased the risk of hypoglycemic events as compared to placebo (no difference was found for hypoglycemic events below 3.0 mmol/L). The majority of participants were co-treated with insulin.

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). 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.

Safety and efficacy of liraglutide in patients with type 2 diabetes and end-stage renal disease: protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded, parallel intervention study.

INTRODUCTION: Diabetes is the leading cause of end-stage renal disease (ESRD). Owing to renal clearance, several antidiabetic agents cannot be used in patients with ESRD. The present protocol describes an investigator-initiated trial aiming to test safety and efficacy of treatment with the glucagon-like peptide-1 receptor agonist liraglutide in patients with type 2 diabetes and dialysis-dependent ESRD. METHODS AND ANALYSIS: Twenty patients with type 2 diabetes and ESRD will be compared with 20 matched patients with type 2 diabetes and normal kidney function in a randomised, parallel, placebo-controlled (1 : 1), double-blinded setting. All participants will receive 12 weeks of daily treatment with liraglutide/placebo in an individually titrated dose of 0.6, 1.2 or 1.8 mg. Over nine visits, plasma liraglutide, glycaemic control, ß-cell response, cardiovascular parameters, various biomarkers and adverse events will be assessed. The primary endpoint will be evaluated from dose-corrected plasma trough liraglutide concentration at the final trial visit to determine potential accumulation in the ESRD group. ETHICS AND DISSEMINATION: The study has been approved by the Danish Medicines Agency, the Scientific-Ethical Committee of the Capital Region of Denmark and the Danish Data Protection Agency. An external monitoring committee (The Good Clinical Practice Unit at Copenhagen University Hospitals) will oversee the study. The results of the study will be presented at national and international scientific meetings, and publications will be submitted to peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01394341.