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 insulin glargine and lixisenatide (iGlarLixi) versus lixisenatide (Lixi) in insulin-naïve Japanese patients with type 2 diabetes mellitus inadequately controlled on oral antidiabetic drugs (OADs).

RESEARCH DESIGN AND METHODS: In this phase 3, open-label, multicenter trial, 321 patients with HbA_1c ≥7.5 to ≤10.0% (58 to 86 mmol/mol) and fasting plasma glucose (FPG) ≤13.8 mmol/L (250 mg/dL) were randomized 1:1 to iGlarLixi or Lixi for 52 weeks. The primary end point was change in HbA_1c at week 26.

RESULTS: Change in HbA_1c from baseline to week 26 was significantly greater with iGlarLixi (−1.58% [−17.3 mmol/mol]) than with Lixi (−0.51% [−5.6 mmol/mol]), confirming the superiority of iGlarLixi; least squares [LS] mean difference −1.07% [−11.7 mmol/mol], P < 0.0001). At week 26, significantly greater proportions of patients treated with iGlarLixi reached HbA_1c <7% (53 mmol/mol; 65.2% vs. 19.4%; P < 0.0001) and FPG reductions were greater with iGlarLixi than Lixi (LS mean difference −2.29 mmol/L [−41.23 mg/dL], P < 0.0001). Incidence of documented symptomatic 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 either group. Incidence of gastrointestinal events through week 52 was lower with iGlarLixi (36.0% vs. 50.0%); rates of treatment-emergent adverse events were similar.

CONCLUSIONS: This phase 3 study demonstrated superior glycemic control and fewer gastrointestinal adverse events with iGlarLixi than with Lixi, which may support it as a new treatment option for Japanese patients with type 2 diabetes inadequately controlled on OADs.