Switching to iGlarLixi Versus Continuing Daily or Weekly GLP-1 RA in Type 2 Diabetes Inadequately Controlled by GLP-1 RA and Oral Antihyperglycemic Therapy: The LixiLan-G Randomized Clinical Trial

OBJECTIVE: Fixed-ratio combinations of basal insulin plus glucagon-like peptide 1 receptor agonist (GLP-1 RA) allow concomitant administration of two proven complementary injectable therapies for type 2 diabetes. This study investigated switching to a titratable fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) in patients with type 2 diabetes receiving daily or weekly GLP-1 RA therapy. RESEARCH DESIGN AND METHODS: 7-9% (53-75 mmol/mol) taking maximum tolerated doses of a GLP-1 RA daily (60% on liraglutide once daily or exenatide twice daily) or weekly (40% on dulaglutide, exenatide extended release, or albiglutide) with metformin with or without pioglitazone and with or without sodium-glucose cotransporter 2 inhibitors. Adherence to randomized treatment was closely monitored throughout the study. RESULTS: <7% without documented symptomatic hypoglycemia (<54 mg/dL). Nausea and vomiting rates as well as numbers of documented symptomatic hypoglycemia events per patient-year were generally low but greater with iGlarLixi versus continued GLP-1 RA therapy. CONCLUSIONS: Switching to iGlarLixi improves glucose control for patients with type 2 diabetes insufficiently controlled on a maximum tolerated dose of a GLP-1 RA plus oral antihyperglycemic agents.