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Meta-Analysis
. 2017 Nov;19(11):1594-1601.
doi: 10.1111/dom.12986. Epub 2017 Jun 7.

Efficacy and safety of lixisenatide in patients with type 2 diabetes and renal impairment

Markolf Hanefeld  1 , Juan M Arteaga  2 , Lawrence A Leiter  3 , Giulio Marchesini  4 , Elena Nikonova  5 , Marina Shestakova  6   7 , William Stager  8 , Ricardo Gómez-Huelgas  9   10   11
Affiliations
Meta-Analysis

Efficacy and safety of lixisenatide in patients with type 2 diabetes and renal impairment

Markolf Hanefeld et al. Diabetes Obes Metab. 2017 Nov.

Abstract

Aims: This post hoc assessment evaluated the efficacy and safety of once-daily, prandial glucagon-like peptide-1 receptor agonist lixisenatide in patients with type 2 diabetes (T2D) and normal renal function (estimated glomerular filtration rate ≥90 mL/min), or mild (60-89 mL/min) or moderate (30-59 mL/min) renal impairment.

Methods: Patients from 9 lixisenatide trials in the GetGoal clinical trial programme were categorized by baseline creatinine clearance: normal renal function (lixisenatide n = 2094, placebo n = 1150); renal impairment (mild: lixisenatide n = 637, placebo n = 414; moderate: lixisenatide n = 122, placebo n = 68). Meta-analyses of placebo-adjusted mean differences between baseline renal categories were performed for efficacy and safety outcomes.

Results: HbA1c, 2-hour postprandial plasma glucose and fasting plasma glucose were comparably reduced in lixisenatide-treated patients with normal renal function, and mild and moderate renal impairment. The most common adverse events (AEs) in all renal function categories were gastrointestinal (GI), predominantly nausea and vomiting. A 14% higher incidence of GI AEs and a 10% higher incidence of nausea and vomiting were seen with mild impairment vs normal function (P = .003 for both), but no significant differences were observed between the mild and moderate impairment categories (P = .99 and P = .57, respectively), or between the moderate impairment and normal categories (P = .16 and P = .65, respectively). Additionally, the incidence of hypoglycaemia was similar in all categories.

Conclusions: This study demonstrates that baseline renal status does not affect efficacy outcomes in lixisenatide- vs placebo-treated patients, and that no lixisenatide dose adjustment is required for patients with T2D with mild or moderate renal impairment.

Keywords: GLP-1; incretin therapy; meta-analysis; type 2 diabetes.

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Conflict of interest statement

M. H. has served on an advisory panel and as an author for Bristol‐Myers Squibb, GlaxoSmithKline, Sanofi and Takeda; and has served on a speakers’ bureau and as an author for Bayer Health Care, Eli Lilly, GlaxoSmithKline, Roche, Sanofi and Takeda. J. M. A. has served on an advisory panel and as an author for AstraZeneca, Bristol‐Myers Squibb, Novo Nordisk and Sanofi; and as a speaker for Sanofi. L. A. L. has received research funding from, has provided CME on behalf of, and/or has served as an adviser to AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novo Nordisk, Pfizer, Sanofi, Servier and Takeda. G. M. has received research support from and served as an author for MSD; has served on a speakers’ bureau and as an author for Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Novo Nordisk and Sanofi; and has served on an advisory panel for Boehringer Ingelheim, Eli Lilly and Sanofi. E. N. is an employee of Artech Information Systems, under contract with Sanofi as a clinical data associate. M. S. has served on an advisory panel and as an author for Novo Nordisk; has received research support from and served as an author for Novartis; and has served on speakers’ bureau and as an author for AstraZeneca, Boehringer Ingelheim, Bristol‐Myers Squibb, Eli Lilly, MSD, Novartis, Novo Nordisk and Servier. W. S. is an employee of Sanofi. R. G.‐H. has served on an advisory panel and as an author for Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi.

Figures

Figure 1
Figure 1
Placebo‐adjusted meta‐analysis of change in A, HbA1c; B, 2‐hour PPG and C, FPG from baseline to week 24 (week 12 for GetGoal‐Mono) between renal function categories in patients receiving lixisenatide. Normal renal function: eGFR ≥90 mL/min; mild impairment: eGFR 60‐89 mL/min; moderate impairment: eGFR 30‐59 mL/min. CI, confidence interval; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HbA1c, glycated haemoglobin; PPG, postprandial plasma glucose
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