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 oftwoproven 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 LixiLan-G, a randomized, open-label, 26-week trial, compared switching to iGlarLixi versus continuing prior GLP-1 RA in patients with type 2 diabetes and HbA1c 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 iGlarLixi (n5257) reduced HbA_1c more than continued GLP-1 RA therapy (n5257) from a baseline 7.8% (62 mmol/mol) in both to 6.7% (50 mmol/mol) and 7.4% (57 mmol/mol), respectively, at 26 weeks (least squares mean difference20.6%; P < 0.0001). More iGlarLixi patients achieved HbA1c <7% (53 mmol/mol) (62% vs. 26%; P < 0.0001) and the composite of HbA_1c <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.