1004-P: Oral Semaglutide vs. Placebo in Patients with Type 2 Diabetes and Moderate Renal Impairment: PIONEER 5

Patients (pts) with T2D and renal impairment have limited glucose-lowering treatment options. Oral semaglutide (sema) 14 mg once daily (N=163) was compared with placebo (pbo, N=161) in a 26-week, randomized, phase 3a trial (NCT02827708) in pts with T2D and moderate renal impairment (eGFR 30-59 mL/min/1.73 m2), receiving 1-2 glucose-lowering agents (could include basal insulin). Endpoints: change in HbA1c (primary) and body weight (BW, secondary) to week 26. Two estimands were defined: treatment policy (regardless of trial product discontinuation or rescue medication) and trial product (on trial product without rescue medication) in all randomized pts. Oral sema was superior to (treatment policy) and significantly better than (trial product) pbo in reducing HbA1c and BW (Table). More pts reached HbA1c, BW loss, and composite targets with oral sema. At follow-up, eGFR was unchanged. Fewer pts on oral sema required rescue medication (4 vs. 10%). Adverse events were more frequent with oral sema (74 vs. 65%), most often mild/moderate nausea (19 vs. 7%). More patients on oral sema prematurely discontinued trial product (15 vs. 5%), mainly due to nausea and vomiting. In conclusion, in pts with T2D and moderate renal impairment, oral sema provided superior glycemic control and BW loss compared to pbo at 26 weeks, did not appear to affect renal function, and was well tolerated in line with the population and GLP-1RA class. Disclosure O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. S. Rosenlund: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J.W. Eriksson: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. S.R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi-Aventis, Takeda Pharmaceutical Company Limited, Zealand Pharma A/S. Consultant; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. R.E. Pratley: Consultant; Self; Sanofi US. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Janssen Global Services, LLC., Janssen Research & Development, Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk Inc., Pfizer Inc., Sanofi, Takeda Development Center Americas, Inc. T. Sathyapalan: Speaker's Bureau; Self; Novo Nordisk Foundation. Other Relationship; Self; Bristol-Myers Squibb Company, Eli Lilly and Company, Sanofi-Aventis. T.M. Blicher: Employee; Self; Novo Nordisk A/S. O.H. Hels: Employee; Self; Novo Nordisk A/S. C. Desouza: Consultant; Self; Novo Nordisk A/S, Sanofi US. Funding Novo Nordisk A/S