721-P: Insulin-Sparing Effects of Oral Semaglutide: An Analysis of PIONEER 8
Authors: ARODA VANITA R. , ABILDLUND MORTEN T. , AGESEN RIKKE , HARRIS STEWART B. , ZAHEDI BANAFSHEH , ZINMAN BERNARD , ARAKI EIICHI 
Published: May 2022

The PIONEER 8 (NCT03021187) trial demonstrated significant glucose-lowering efficacy of oral semaglutide vs. placebo (pbo) in patients (pts) with T2D inadequately controlled with insulin. Additionally, those assigned to oral semaglutide (7 or 14 mg daily) had a lower total daily insulin dose at end of treatment (week 52) relative to baseline, vs. those treated with pbo, suggesting an insulin-sparing effect. This post-hoc analysis of PIONEER 8 aimed to characterize the transition of adding a GLP-1RA to insulin therapy and to quantify reductions in total insulin dose seen with the addition of oral semaglutide. A 20% reduction in total daily insulin dose was recommended at randomization up to week 8. Total daily insulin was not to exceed pre-randomization dose between weeks 8 and 26 but was freely adjustable at the investigator’s discretion from week 26 to 52. For all doses of oral semaglutide, a greater proportion of pts were able to maintain a greater level of insulin dose reduction vs. pbo at week 26 (Figure) . Greater proportions of pts on oral semaglutide 3, 7, and 14 mg achieved ≥20% reductions in insulin vs. those in the pbo group at both weeks 26 and 52 (Treatment policy estimand; 27.5%, 28.9%, 31.2% vs. 12.4% and 19.5%, 25.0%, 32.0% vs 5.7%, respectively; P&lt;0.0 for all) . Addition of oral semaglutide in pts with T2D permits a significant reduction in insulin dose, which may provide benefits (e.g. lower risk of hypoglycemia and weight gain) long-term.

Disclosure
V.R.Aroda: Consultant; Applied Therapeutics, Fractyl Health, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Other Relationship; Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Research Support; Applied Therapeutics, Fractyl Health, Inc., Novo Nordisk, Sanofi. M.T.Abildlund: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. R.Agesen: Employee; Novo Nordisk A/S. S.B.Harris: Consultant; Abbott, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Other Relationship; Abbott, AstraZeneca, Bayer Inc., Dexcom, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Applied Therapeutics Inc., AstraZeneca, Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF) , Novo Nordisk, Sanofi, The Lawson Foundation. B.Zahedi: Employee; Novo Nordisk A/S. B.Zinman: Advisory Panel; Abbott Diabetes, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi K.K. E.Araki: Other Relationship; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly and Company, Kowa Company, Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk, Sanofi K.K., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Corporation, Speaker's Bureau; Abbott, AstraZeneca, Kyowa Kirin Co., Ltd., Ono Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho.

Funding
Funded by Novo Nordisk A/S