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

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.

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