985-P: Oral Semaglutide as Add-On to Insulin in T2D: PIONEER 8
Authors: ZINMAN BERNARD , ARODA VANITA R. , BUSE JOHN B. , CARIOU BERTRAND , HARRIS STEWART B. , HOFF SOREN T. , PEDERSEN KAREN BOJE , TARP-JOHANSEN MADS JEPPE , ARAKI EIICHI ,   FOR THE PIONEER 8 INVESTIGATORS
Published: June 2019

Patients (pts) with T2D uncontrolled on insulin ± metformin were randomized to oral semaglutide (sema) 3 mg (N=184), 7 mg (N=182) or 14 mg (N=181), or placebo (pbo; N=184) in a 52-week (week) double-blind trial (NCT03021187). Total daily insulin dose was reduced by an optional 20% and capped at baseline (BL) level for week 0-26 and freely adjustable for week 26-52. Endpoints were change from BL to week 26 in HbA1c (primary) and body weight (BW; confirmatory secondary). Two scientific questions were addressed by defining two estimands: a treatment policy estimand (regardless of trial product discontinuation or rescue medication use), and a trial product estimand (on trial product without rescue medication use) in all randomized pts. Oral sema was superior to pbo in reducing HbA1c and BW at week 26 (treatment policy estimand). Significantly greater, dose-dependent HbA1c and BW reductions vs. pbo were achieved at week 26 and 52 (both estimands; Table). Total daily insulin dose was significantly reduced from BL with oral sema vs. pbo at week 26 (except 3 mg) and 52. The rate of hypoglycemia was not significantly different vs. pbo (Table). Most frequent AE with oral sema was nausea (11.4-23.2% of pts vs. 7.1% with pbo) and 7.1-13.3% of pts prematurely discontinued due to AEs (vs. 2.7% with pbo). As add-on to insulin ± metformin, oral sema had superior HbA1c and BW reductions vs. pbo at week 26. It also reduced insulin use by week 52 and was well tolerated without significantly increasing hypoglycemia rate.

Disclosure
B. Zinman: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. 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. 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. B. Cariou: Board Member; Self; Novo Nordisk A/S, Regeneron Pharmaceuticals. Consultant; Self; GENFIT, Sanofi-Aventis. Research Support; Self; Amgen Inc., Pfizer Inc. Speaker's Bureau; Self; Abbott, Akcea Therapeutics, Merck Sharp & Dohme Corp. S.B. Harris: Advisory Panel; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, AstraZeneca, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; Canadian Diabetes Association, Canadian Institutes of Health Research, The Lawson Foundation. S.T. Hoff: Employee; Self; Novo Nordisk A/S. K. Pedersen: Employee; Self; Novo Nordisk A/S. M. Tarp-Johansen: Employee; Self; Novo Nordisk A/S. E. Araki: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Novo Nordisk Inc., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Merck & Co., Inc., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi.

Funding
Novo Nordisk A/S