Efficacy and Safety of 1:1 Fixed Ratio Combination of Insulin Glargine/Lixisenatide (iglarlixi) Versus Lixisenatide in Japanese Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Oral Antidiabetic Drugs: the LixiLan JP-O1 Randomized Clinical Trial

OBJECTIVE:To assess the efficacy and safety of a 1:1 fixed ratio combination of insulinglargine and lixisenatide (iGlarLixi) versus lixisenatide (Lixi) ininsulin-naïve Japanese patients with type 2 diabetes mellitus inadequatelycontrolled on oral antidiabetic drugs (OADs). RESEARCHDESIGN AND METHODS: In this phase 3, open-label, multicenter trial, 321patients with HbA1c ≥7.5 to ≤10.0% (58 to 86 mmol/mol) and fasting plasma glucose (FPG) ≤13.8 mmol/L (250mg/dL) were randomized 1:1 to iGlarLixi or Lixi for 52 weeks. The primary end pointwas change in HbA1c at week 26. RESULTS:Change in HbA1c from baseline toweek 26 was significantly greater with iGlarLixi (−1.58% [−17.3 mmol/mol]) than with Lixi (−0.51% [−5.6 mmol/mol]), confirmingthe superiority of iGlarLixi; least squares [LS] mean difference −1.07% [−11.7mmol/mol], P < 0.0001). At week 26, significantly greater proportionsof patients treated with iGlarLixi reached HbA1c <7% (53 mmol/mol; 65.2% vs. 19.4%; P < 0.0001)and FPG reductions were greater with iGlarLixi than Lixi (LS mean difference −2.29mmol/L [−41.23 mg/dL], P < 0.0001). Incidence of documentedsymptomatic hypoglycemia (≤3.9 mmol/L [70 mg/dL]) was higher with iGlarLixi(13.0% vs. 2.5%) through week 26, with no severe hypoglycemic events in eithergroup. Incidence of gastrointestinal events through week 52 was lower withiGlarLixi (36.0% vs. 50.0%); rates of treatment-emergent adverse events weresimilar. CONCLUSIONS:This phase 3 study demonstratedsuperior glycemic control and fewer gastrointestinal adverse events withiGlarLixi than with Lixi, which may support it as a new treatment option for Japanese patients with type 2 diabetesinadequately controlled on OADs.