Mild Renal Impairment and the Efficacy and Safety of Liraglutide

Abstract

Objective To determine the effect of mild renal impairment (RI) on the efficacy and safety of liraglutide in patients with type 2 diabetes mellitus. Methods In this meta-analysis, we examined the 6 LEAD (Liraglutide Effect and Action in Diabetes) studies. Data from patients with type 2 diabetes who had normal renal function, mild RI, or moderate or severe RI were pooled for analysis. Renal function was measured by creatinine clearance as determined by the Cockcroft-Gault equation: normal renal function = creatinine clearance >89 mL/min; mild RI = 60 mL/min ≤ creatinine clearance ≤ 89 mL/min; and moderate or severe RI = creatinine clearance <60 mL/min. The meta-analysis included patients administered once-daily liraglutide (1.2 or 1.8 mg) or placebo as either monotherapy or in combination with oral antidiabetic drugs for 26 weeks. In addition, a pooled analysis of all phase 2 and 3 liraglutide trials was done to examine rates of altered renal function. Results Mild RI did not affect the estimated treatment differences in hemoglobin A1c. Patients with normal renal function demonstrated decreases in body weight and systolic blood pressure with either dosage of liraglutide, whereas patients in either RI group also demonstrated a decrease in body weight and systolic blood pressure, but these differences were not significant compared with differences observed in the placebo group. Liraglutide treatment vs placebo was safe and well tolerated in patients with mild RI, as there were no significant differences in rates of renal injury, minor hypoglycemia, or nausea. A trend towards increased nausea was observed in patients with moderate or severe RI receiving liraglutide, although the number of patients in this treatment group was too low to determine significance. Conclusion Mild RI, as determined by the CockcroftGault equation, had no effect on the efficacy and safety of liraglutide in this meta-analysis. (Endocr Pract. 2011; 17:345-355)