6-LB: Effect of Open-Label SGLT2 Inhibitor Treatment When Combined with Exenatide on Cardiovascular and Renal Outcomes in EXSCEL

Abstract

SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) improve cardiovascular (CV) and renal outcomes through distinct mechanisms. However, evidence is lacking on clinical outcomes in patients treated with both classes. EXSCEL, the cardiovascular outcomes trial for the GLP-1 RA exenatide, provides an opportunity to explore CV and renal outcomes with dual GLP-1RA and SGLT2i treatment, as ∼10% of participants had an SGLT2i added to their glycemic management during follow-up. Cohorts of SGLT2i users in the exenatide arm were propensity-matched to: 1) users of exenatide but not SGLT2i; 2) placebo arm participants that did not take SGLT2i, based on last measured characteristics before SGLT2i initiation. Subsequent time-to-first adjudicated major adverse cardiovascular event (MACE) and all-cause mortality (ACM) were compared using Cox regression analyses. eGFR decline was quantified in the matched cohorts using a mixed model repeated measurement (MMRM) analysis. Exenatide plus SGLT2i use numerically decreased the MACE hazard ratio and significantly reduced ACM risk, compared with exenatide alone and with placebo. The combination also significantly improved eGFR slope in both comparisons. This post hoc analysis offers support for the hypothesis that combinatorial exenatide and SGLT2i use may provide benefit on renal function and all-cause mortality. Disclosure L.E. Clegg: Employee; Self; AstraZeneca. R.C. Penland: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca, Novartis AG. D.W. Boulton: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca, Bristol-Myers Squibb Company. S. Bachina: Employee; Self; AstraZeneca. M. Thuresson: Consultant; Self; AstraZeneca. H.L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation. S. Gustavson: Employee; Self; AstraZeneca. Employee; Spouse/Partner; AstraZeneca. C. Sjöström: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. J.A. Ruggles: Employee; Self; AstraZeneca. Stock/Shareholder; Self; Apple, AstraZeneca. A.F. Hernandez: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. J.B. Buse: Consultant; Self; Neurimmune AG. Research Support; Self; AstraZeneca, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk A/S, Sanofi, vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg, Novo Nordisk A/S, Senseonics, vTv Therapeutics, Zafgen, Inc. R.J. Mentz: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; GlaxoSmithKline plc. Other Relationship; Self; Amgen Inc., AstraZeneca, Bayer AG, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. R.R. Holman: Advisory Panel; Self; Bayer AG, Novartis AG, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp. Other Relationship; Self; AstraZeneca, Bayer AG, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc.