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The effect of lixisenatide—a prandial once-daily glucagon-like peptide-1 receptor agonist—on glycaemic control in patients with inadequately controlled type 2 diabetes mellitus (T2DM), stratified by baseline β-cell function, was assessed.The 24-week GetGoal-M, -P and -S trials evaluated the efficacy and safety of lixisenatide in combination with oral antidiabetic agents. This post hoc analysis used data from patients receiving lixisenatide in these trials, divided into matched cohorts by propensity scoring, and stratified according to baseline homeostasis model assessment of β-cell function (HOMA-β) index levels, high HOMA-β: > median HOMA-β (28.49%); low HOMA-β: ≤ median.The matched “low” and “high” HOMA-β index cohorts (N = 546 patients) had comparable baseline parameters. Mean change from baseline in glycated haemoglobin (HbA1c) was −0.85% and −0.94% for low and high HOMA-β cohorts, respectively (P = .2607). Reductions from baseline in fasting plasma glucose (FPG; −0.77 vs −1.04 mmol/L; P = .1496) and postprandial plasma glucose (PPG; −5.82 vs −5.61 mmol/L; P = .7511) were similar in the low versus high HOMA-β index cohorts. Reduction in body weight was significantly greater in the low versus high HOMA-β index cohort (–2.06 vs –1.13 kg, respectively; P = .0006).In patients with T2DM, lixisenatide was associated with reduction in HbA1c and improvements in both FPG and PPG, regardless of β-cell function, indicating that lixisenatide is effective in reducing hyperglycaemia, even in patients with more advanced stages of T2DM and poor residual β-cell function.