Elsevier

Endocrine Practice

Volume 17, Issue 3, May–June 2011, Pages 345-355
Endocrine Practice

Original Article
Mild Renal Impairment and the Efficacy and Safety of Liraglutide

https://doi.org/10.4158/EP10215.ORGet rights and content

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)

Section snippets

INTRODUCTION

Type 2 diabetes mellitus (T2DM) is a major risk factor for progressive chronic kidney disease, and approximately 20% to 40% of patients with T2DM develop diabetic nephropathy. Worldwide, diabetic nephropathy is the leading cause of end-stage renal disease (1). Treatment considerations that address glycemia for diabetic patients with renal impairment (RI) are complex and limited, and there is no consensus on how to most safely achieve the recommended glycemic targets. The ability to achieve

METHODS

Study Selection and Inclusion Criteria

Data for this meta-analysis were pooled from the LEAD (Liraglutide Effect and Action in Diabetes) clinical trials. The LEAD studies consisted of 6 phase 3, multicenter, parallel-group, placebo and active-controlled trials (17., 19., 20., 23, 24). Five of the LEAD trials assessed the efficacy and safety of liraglutide in combination with oral antidiabetic drugs, and 1 LEAD trial tested liraglutide as monotherapy. A total of 2783 patients with T2DM taking

RESULTS

This meta-analysis included 896 patients taking liraglutide, 1.2 mg daily, 1363 patients taking liraglutide, 1.8 mg daily, and 524 patients taking placebo (background therapy included). No significant differences were observed in patient characteristics at baseline (Table 1), although patients with mild RI and moderate or severe RI tended to be older and had a longer duration of diabetes. The proportion of patients with normal renal function, mild RI, and moderate or severe RI were similar

DISCUSSION

The results of this meta-analysis indicate that the efficacy and safety of liraglutide in patients with T2DM are not affected by mild RI. CrCl did not significantly affect the change in hemoglobin A1c or the percentage of patients reaching glycemic targets with liraglutide. This finding further supports the results from an earlier study that showed the pharmacokinetics of liraglutide are not influenced by varying degrees of RI (22).

Another significant finding from this analysis is the ability

CONCLUSION

This meta-analysis provides initial evidence that once-daily liraglutide is safe and effective in patients with T2DM and mild RI. Patients with T2DM and mild RI demonstrated similar rates of glycemic control, hypoglycemia, and nausea as patients with normal renal function. These findings indicate that liraglutide is a viable treatment option in patients with T2DM who have mild RI. However, further studies and more experience in patients with T2DM and more advanced degrees of renal failure will

DISCLOSURE

Dr. Davidson is president of WorldWIDE Diabetes and has served as a consultant and participated in advisory boards and/or speakers’ bureaus for Abbott Laboratories, Animas, Astra-Zeneca, Bristol Myers Squibb, Cure-DM, Eli Lilly & Company, Generex, Glaxo-SmithKline, Johnson & Johnson (Lifescan), Merck-Serono, MerckSharp and Dome, Novo Nordisk, Novartis, Pfizer, Roche, sanofi-aventis, and Takeda. Dr. Scott has served on advisory boards and/or speakers’ bureaus for Novo Nordisk, Orthobiotech,

ACKNOWLEDGMENT

The authors thank Aji Nair, PhD, and Ashwini Dhume, PhD, both of Novo Nordisk, Inc, for medical writing assistance.

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