Efficacy and safety of insulin glargine/lixisenatide fixed‐ratio combination (iGlarLixi) in Japanese patients with type 2 diabetes mellitus inadequately controlled on basal insulin and oral antidiabetic drugs: The LixiLan JP‐L randomized clinical trial

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>To assess efficacy and safety of fixed‐ratio (1:1) combination insulin glargine and lixisenatide (iGlarLixi) compared to insulin glargine U100 (iGlar), with metformin, in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on basal insulin and oral antidiabetic drugs (OADs).</jats:p></jats:sec><jats:sec><jats:title>Materials and methods</jats:title><jats:p>This 26‐week, randomized, open‐label study compared iGlarLixi to iGlar, both with metformin in adult Japanese patients with T2DM and hemoglobin (Hb) A1c ≥7.5% to ≤9.5%, treated with basal insulin and 1 or 2 OADs. Five hundred and twelve patients were randomized after a 12‐week run‐in, when iGlar was introduced and/or further titrated and OADs other than metformin were stopped. The primary endpoint was change in HbA1c from baseline to week 26.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>iGlarLixi (n = 255) demonstrated significantly greater reductions in HbA1c (−1.27%) than iGlar (n = 257, −0.53%) (LS mean difference: –0.74%, <jats:italic>P</jats:italic> < .0001) at week 26, confirming the superiority of iGlarLixi. Significantly, more iGlarLixi patients reached target HbA1c <7% at week 26 (51.8% vs 16.0% for iGlar). iGlarLixi patients lost weight in contrast to iGlar patients (−0.51 kg vs +0.55 kg). Documented symptomatic hypoglycemia (plasma glucose ≤ 3.9 mmol/L) was observed in 18.8% of iGlarLixi patients vs 16.7% of iGlar patients. iGlarLixi patients had more gastrointestinal‐related adverse events than iGlar patients (33.3% vs 8.6%), primarily nausea (16.9% vs 0.8%). However, the treatment was generally well‐tolerated.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>A once‐daily injection of iGlarLixi with metformin is an effective, well‐tolerated, and simple therapeutic intervention providing significant improvement in glycemic control in Japanese patients with T2DM inadequately controlled on basal insulin and up to two OADs.</jats:p><jats:p>Clinical Trial Number: NCT02752412.</jats:p></jats:sec>