A Review of the Safety and Adverse Event Profile of the Fixed-Ratio Combination of Insulin Glargine and Lixisenatide.

INTRODUCTION: iGlarLixi is a titratable, fixed-ratio combination of insulin glargine (100 units/mL) and lixisenatide (33 μg/mL). This review evaluates the overall safety and adverse event (AE) profile of iGlarLixi in patients with type 2 diabetes.

METHODS: We collated patient-level data from the phase 2 LixiLan proof-of-concept trial and the phase 3 LixiLan-L (insulin-experienced patients) and LixiLan-O (insulin-naïve patients) trials to evaluate AEs associated with iGlarLixi. We also describe data from the ELIXA study to examine pancreatitis and pancreatic cancer, and the ELIXA and ORIGIN studies for cardiovascular safety data.

RESULTS: Patients treated with iGlarLixi had improved glycemic control with a similar incidence of documented symptomatic hypoglycemia (plasma glucose ≤ 70 mg/dL) compared with iGlar. Incidence of severe hypoglycemia (an event requiring third-party assistance) was low in all treatment arms in both LixiLan-L and LixiLan-O. Rates of gastrointestinal AEs in patients treated with iGlarLixi tended to be lower compared with lixisenatide alone, but higher than those treated with iGlar alone. Gastrointestinal AEs were generally mild to moderate in intensity and transient. Antibodies formed in response to iGlarLixi did not have any significant clinical impact, with similar safety observed for antibody-positive and antibody-negative populations. Rates of allergic reactions, malignancy, renal impairment, and cardiovascular events were low and comparable between treatment groups. Older age (≥ 65 years) and gender did not affect efficacy or safety.

CONCLUSION: iGlarLixi has a safety profile that is consistent with that of its two active components insulin glargine and lixisenatide, with no signals for pancreatitis or thyroid C cell tumors, and no black-box warning for iGlarLixi. There were no unexpected safety findings; iGlarLixi had beneficial effects on glycemic control, with no increased risk of hypoglycemia, despite a greater glycated hemoglobin A1c reduction. In addition, there were also fewer gastrointestinal AEs associated with iGlarLixi compared with lixisenatide alone.

FUNDING: Sanofi US Inc.