Renal Outcomes in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL)

• Published in: Diabetes (New York, N.Y.) Vol. 67; no. Supplement_1
• Main Authors: BETHEL, M. ANGELYN, MENTZ, ROBERT J., MERRILL, PETER, BUSE, JOHN B., CHAN, JULIANA C., GOODMAN, SHAUN G., IQBAL, NAYYAR, JAKUBONIENE, NELI, KATONA, BRIAN G., LOKHNYGINA, YULIYA, LOPES, RENATO D., MAGGIONI, ALDO P., OHMAN, PETER K., POULTER, NEIL R., RAMACHANDRAN, AMBADY, TANKOVA, TSVETALINA, ZINMAN, BERNARD, HERNANDEZ, ADRIAN F., HOLMAN, RURY R.
• Format: Journal Article
• Language: English; Japanese
• Published: 01-07-2018
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db18-522-P

Background: EXSCEL was a multinational, randomized, blinded, placebo-controlled, pragmatic CV outcome trial of once-weekly exenatide on the background of usual care. We report exenatide’s impact on estimated glomerular filtration rate (eGFR), new macroalbuminuria and 2 renal composites from a prespecified analysis plan.
Methods: Opportunistic local laboratory data were collected. Overall least squares mean difference (LSMD) eGFR (95% confidence interval [95% CI]) was calculated for 13844 patients with baseline and ≥1 follow-up value. Effect on new macroalbuminuria was estimated with a Cox regression model. Effects on renal composites were estimated with interval censored time to event models, with and without covariate adjustment (demographics and disease characteristics).
Results: Intention-to-treat analyses showed no significant difference in eGFR levels with exenatide (LSMD +0.21 [-0.27, 0.70] mL/min.1.73m2, p=0.39). New macroalbuminuria occurred in 2.2% and 2.5% of the exenatide and placebo groups (p=0.19). There was a 15% lower renal composite 2 adjusted risk with exenatide (p=0.027) (Table).
Conclusions: A composite of 40% eGFR decline, renal replacement, renal death or new macroalbuminuria was significantly reduced in an adjusted analysis by the addition of exenatide in a broad range of people with type 2 diabetes. Other renal outcomes were numerically but not statistically improved with exenatide.
Disclosure
M. Bethel: Research Support; Self; AstraZeneca, Merck Sharp & Dohme Corp., Merck Serono. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca. Other Relationship; Self; Sanofi. Consultant; Self; Theracos, Inc.. Research Support; Self; GlaxoSmithKline plc. R.J. Mentz: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc.. P. Merrill: None. J.B. Buse: Other Relationship; Self; ADOCIA, AstraZeneca, Dexcom, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Fractyl Laboratories, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Metavention, NovaTarg, Novo Nordisk A/S, Sanofi, VTV Therapeutics. Research Support; Self; Boehringer Ingelheim GmbH, Johnson & Johnson Services, Inc., Theracos, Inc.. Other Relationship; Self; Shenzhen Hightide Biopharmaceutical, Ltd.. Research Support; Self; National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association. Research Support; Self; Patient-Centered Outcomes Research Institute. Other Relationship; Self; National Institute of Environmental Health Sciences. J.C. Chan: Consultant; Self; Bayer AG. Other Relationship; Self; Bayer AG. Consultant; Self; Sanofi. Other Relationship; Self; Sanofi, Eli Lilly and Company, Amgen Inc.. Consultant; Self; AstraZeneca, Merck & Co., Inc., Pfizer Inc.. Other Relationship; Self; Pfizer Inc.. Board Member; Self; Asia Diabetes Foundation. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; Merck Sharp & Dohme Corp.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Eli Lilly and Company. S.G. Goodman: Research Support; Self; Amgen Inc.. Consultant; Self; Amgen Inc.. Research Support; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; Bayer AG. Consultant; Self; Bayer AG. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Bristol-Myers Squibb Company. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Consultant; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Research Support; Self; Pfizer Inc.. Consultant; Self; Pfizer Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc.. Research Support; Self; CSL Behring. N. Iqbal: Employee; Self; AstraZeneca. N. Jakuboniene: None. B.G. Katona: Employee; Self; AstraZeneca. Y. Lokhnygina: None. R.D. Lopes: Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH. Other Relationship; Self; Bristol-Myers Squibb Company. Consultant; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; GlaxoSmithKline plc., Medtronic. Consultant; Self; Merck & Co., Inc.. Other Relationship; Self; Pfizer Inc.. A.P. Maggioni: None. P.K. Ohman: Employee; Self; AstraZeneca. N.R. Poulter: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc.. Research Support; Self; Servier. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc., Servier. Other Relationship; Self; International Society of Hypertension. A. Ramachandran: None. T. Tankova: None. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck & Co., Inc., Abbott. A.F. Hernandez: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc.. Consultant; Self; Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation. R.R. Holman: Research Support; Self; AstraZeneca, Merck & Co., Inc., Bayer AG. Advisory Panel; Self; Elcelyx Therapeutics, Inc., Novartis AG, Novo Nordisk A/S. Other Relationship; Self; Bayer AG. Advisory Panel; Self; Merck & Co., Inc.. Other Relationship; Self; AstraZeneca.