956-P: Efficacy and Safety of Oral Semaglutide When Added to Basal, Premix, or Basal-Bolus Insulin

Abstract

An exploratory subgroup analysis of the 52-week, double-blind PIONEER 8 trial (NCT03021187) evaluated the effect of background insulin regimen (basal, premixed, or basal-bolus) with or without metformin on the efficacy and safety of oral semaglutide (sema). Patients (pts) (N=731) with type 2 diabetes and treated with insulin were randomized to once-daily oral sema (3, 7, or 14 mg) or placebo (pbo). Endpoints included change from baseline in HbA1c, body weight (BW), and total daily insulin dose at week 52. Baseline age and HbA1c were similar across insulin regimen subgroups whereas BW was greater and diabetes duration was longer in pts on basal-bolus vs. basal and premix subgroups. There were greater dose-dependent HbA1c and BW reductions with oral sema vs. pbo; these were generally similar across all insulin subgroups (Table). Total daily insulin dose at week 52 was decreased for pts on basal (oral sema 7 and 14 mg), premix (oral sema 14 mg), and basal-bolus (oral sema 3, 7, and 14 mg), mainly driven by the bolus component for pts on basal-bolus (Table). Most hypoglycemic episodes were in pts on basal-bolus insulin. Fewer pts had hypoglycemia with oral sema vs. pbo except in the basal-bolus subgroup (Table). In conclusion, oral sema reduced HbA1c and BW in a dose-dependent manner, and reduced insulin dose regardless of background insulin regimen, with a safety profile similar to other glucagon-like peptide-1 receptor agonists. Disclosure O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd. V.R. Aroda: Consultant; Self; Duke, Novo Nordisk Inc., Sanofi. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Applied Therapeutics, Fractyl Laboratories, Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; IMNE, Medscape. E. Christiansen: None. S.B. Harris: Advisory Panel; Self; Abbott, AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Canadian Institutes of Health Research, Eli Lilly and Company, Health Canada/First Nations and Inuit Health Branch, Janssen Pharmaceuticals, Inc., JDRF, Lawson Foundation, Novo Nordisk Inc., Sanofi. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Sanofi. K. Pedersen: Employee; Self; Novo Nordisk A/S. M. Tarp-Johansen: Employee; Self; Novo Nordisk A/S. B. Zinman: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. Funding Novo Nordisk A/S