Original ArticleMild Renal Impairment and the Efficacy and Safety of Liraglutide
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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