Fixed-ratio combinations (FRCs) of basal insulin plus a GLP-1 receptor agonist (RA) offer simple administration of complementary injectable therapies for T2D. Effects of switching to a titratable FRC of insulin glargine plus lixisenatide (iGlarLixi) in T2D patients (pts) receiving GLP-1 RAs have been unknown. LixiLan-G (NCT02787551), a randomized, open-label, 26-week trial, compared switching to iGlarLixi vs. continuing a GLP-1 RA in T2D pts with HbA1c 7‒9%, receiving a maximum tolerated dose of a QD/BID GLP-1 RA (60% of pts: liraglutide QD, exenatide BID), or a QW GLP-1 RA (40% of pts: dulaglutide, exenatide extended-release, or albiglutide) with metformin ± pioglitazone ± SGLT2i. Adherence to randomized treatment was reinforced and monitored throughout the study. iGlarLixi (n=257) provided greater HbA1c reductions than GLP-1 RA (n=257), from 7.8% at baseline to 6.7% and 7.4%, respectively (LS mean difference [primary endpoint] ‒0.6%; p<0.0001 [Table]). More iGlarLixi pts achieved HbA1c targets and the composite of HbA1c <7% without documented symptomatic hypoglycemia (<54 mg/dL). Documented symptomatic hypoglycemia, nausea, and vomiting rates were low but greater with iGlarLixi vs. GLP-1 RA. In conclusion, switching to iGlarLixi can further improve glucose control for T2D pts receiving the maximum tolerated GLP-1 RA dose with OAD(s). Disclosure L. Blonde: Consultant; Self; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. Research Support; Self; Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Melior Pharmaceuticals, Inc., Bukwang Pharm. Co., Ltd., Merck & Co., Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Board Member; Self; AstraZeneca. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited. R.R. Henry: Advisory Panel; Self; Elcelyx Therapeutics, Inc. Consultant; Self; Diasome Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc. Employee; Self; Eli Lilly and Company. Research Support; Self; AstaReal, Hitachi, Ltd., Viacyte, Inc. Speaker's Bureau; Self; Servier. Other Relationship; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Johnson & Johnson, Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi-Aventis. N. Shehadeh: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. E. Niemoeller: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. E. Souhami: Employee; Self; Sanofi Research & Development. J. Wu: Employee; Self; Sanofi. X. Wang: Employee; Self; Sanofi Research & Development. C. Ji: Employee; Self; Sanofi Research & Development. V.R. Aroda: Consultant; Self; ADOCIA, AstraZeneca, Becton, Dickinson and Company, Novo Nordisk Inc., Sanofi, Zafgen, Inc. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; AstraZeneca, Calibra Medical, Eisai Inc., Janssen Research & Development, Novo Nordisk Inc., Sanofi, Theracos, Inc. Funding Sanofi