Effects of switching to a titratable fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) in patients (pts) with T2D on GLP-1 RAs have been unknown. LixiLan-G (NCT02787551), a randomized, open-label, 26-week trial, compared switching to iGlarLixi vs. continued GLP-1 RA use in pts with T2D and HbA1c 7-9% despite receiving a maximum tolerated dose of a GLP-1 RA (liraglutide QD, exenatide BID, exenatide extended-release QW, albiglutide QW, or dulaglutide QW) with metformin ± pioglitazone ± SGLT2i. Treatment effects seen across baseline factors, such as BMI, GLP-1 RA type, and pioglitazone or SGLT2i use, were consistent with the primary analysis. This exploratory analysis examined HbA1c change at week 26 and documented symptomatic hypoglycemia in 26-week completers (modified ITT) by screening subgroup HbA1c levels (≤7.5%, >7.5-≤8%, and >8%). At week 26, mean HbA1c levels for iGlarLixi were 6.6%, 6.6%, and 6.9%, respectively, vs. 7.2%, 7.4%, and 7.5%, respectively, for GLP-1 RAs. Reductions were greater for iGlarLixi than for GLP-1 RAs in all subgroups (p<0.0001; Figure). Symptomatic hypoglycemia rates were low overall but higher with iGlarLixi than with GLP-1 RAs (Figure).

In conclusion, in pts with T2D inadequately controlled on GLP-1 RA and OAD(s), iGlarLixi demonstrated additional glycemic benefit across a broad range of HbA1c levels.

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Disclosure

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. 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. 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. 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. 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. 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.

Funding

Sanofi

© 2019 by the American Diabetes Association.
2019
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