Introduction: Exenatide is primarily eliminated through the kidneys. Safety/efficacy of exenatide once weekly (EQW) were characterized in patients (pts) with CKD stage 2 and 3 (mild and moderate renal impairment).
Methods: Pts treated with EQW or placebo/non-GLP-1RA comparator drug (sitagliptin, metformin, pioglitazone, dapagliflozin, insulin) from 8 phase 3 double-blind or open-label 26/28-week studies were pooled and stratified by CKD stage. Studies were performed on a broad range of background drugs.
Results: Pts with baseline CKD2 (N=772) or CKD3 (N=182) on EQW differed in some baseline characteristics: age <65 y (79% vs. 56%), mean BMI (31.6 vs. 28.3 kg/m2), and T2D duration (7.6 vs. 9.7 y), while BP (131/79 vs. 133/77) and HbA1c (8.5% vs. 8.3%) were similar. CKD3 EQW pts were mostly Asian (61% vs. 20% CKD2) as 59% of these were from a Japanese study. Efficacy was similar in CKD2 vs. CKD3 pts (Figure).
Rates of any AE were slightly higher in CKD3 vs. CKD2 pts (EQW: 81% vs. 72%; comparators: 74% vs. 68%) and for AEs leading to study or treatment discontinuation (EQW: 8% vs. 5%; comparators: 4% vs. 2%) but similar for SAEs (EQW: 3% vs. 3%; comparators: 6% vs. 5%). One pt in each arm had a SAE of acute kidney injury: EQW in CKD3 and comparator in CKD2 group.
Conclusion: Pooled results of 8 studies show EQW is well tolerated and efficacious in pts with CKD2 and 3. Changes in HbA1c, body weight, and SBP were similar between the 2 CKD groups.
C. Guja: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. J.P. Frias: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Sanofi. Consultant; Self; Echosens, Genentech, Inc., Johnson & Johnson Diabetes Institute, Novo Nordisk Inc., Zafgen, Inc. Research Support; Self; AbbVie Inc., Akcea Therapeutics, Allergan, Amgen Inc., AstraZeneca, Bayer US, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Cirius Therapeutics, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Enanta Pharmaceuticals, Inc., GENFIT, Intarcia Therapeutics, Inc., Intercept Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Oramed Pharmaceuticals, Pfizer Inc., Sanofi, TaiwanJ Pharmaceuticals Co., Ltd., Theracos, Inc. Speaker's Bureau; Self; Merck & Co., Inc., Sanofi. L.J. Suchower: Stock/Shareholder; Self; AstraZeneca, Express Scripts, Merck & Co., Inc. Other Relationship; Self; AstraZeneca. E. Hardy: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. J. Holden: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. C. Sjöström: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. S. Jabbour: Consultant; Self; AstraZeneca, Janssen Pharmaceuticals, Inc.