OR15-3 Robust Dose-Dependent Glucose Lowering and Body Weight (BW) Reductions with the Novel Oral Formulation of Semaglutide in Patients with Early Type 2 Diabetes (T2D)

Program: Abstracts - Orals, Poster Previews, and Posters
Session: OR15-Novel Treatment for Diabetes - Focusing on GLP-1 and SGLT2
Clinical
Saturday, April 2, 2016: 11:45 AM-1:15 PM
Presentation Start Time: 12:15 PM
Room 157 (BCEC)
Serge Jabbour1, Thomas R Pieber2, Julio Rosenstock*3, Marie-Louise Hartoft-Nielsen4, Oluf Kristian Højbjerg Hansen4 and Melanie Davies5
1Thomas Jefferson University, PA, 2Medical University of Graz, Austria, 3Dallas Diabetes and Endocrine Center, TX, 4Novo Nordisk A/S, Søborg, Denmark, 5University of Leicester, United Kingdom
Background GLP-1 therapies are available for the treatment of T2D, but injectable formulations can be a barrier to acceptance and adherence for some patients. A novel oral formulation of the GLP-1 analog, semaglutide, is in development.

Aim Explore the dose–response relationship of oral semaglutide vs placebo (PBO) on glycemic control in patients with T2D.

Methods Adults with T2D on diet/exercise ± metformin (n=632; HbA1c, 7.0–9.5%) were randomized to double-blind oral semaglutide (2.5, 5, 10, 20 or 40 mg once-daily) or PBO; or open-label subcutaneous (s.c.) semaglutide (1.0 mg once‑weekly). A mixed model for repeated measurements was used to analyze the primary endpoint, change in HbA1c from baseline to Week 26, and other continuous endpoints. Two other arms were included to evaluate dose escalations (efficacy data not shown).

Results Baseline characteristics were comparable across treatment groups (mean HbA1c, 7.9%; duration of diabetes, 6 years; BMI, 32 kg/m2); 63% were male and 85% on metformin. Mean HbA1c decreased dose-dependently with oral semaglutide (2.5 mg, 0.7%; 5 mg, 1.2%; 10 mg, 1.5%; 20 mg, 1.7%; 40 mg, 1.9%) vs 1.9% for s.c. semaglutide and 0.3% for PBO, and was statistically significant vs PBO (p=0.07 for 2.5 mg, <0.0001 for other doses). Reductions in FPG were greater with oral (17–51 mg/dL; p=0.08 for 2.5 mg, <0.0001 for other doses) and s.c. (56 mg/dL) semaglutide vs PBO (1 mg/dL). The proportion of patients achieving HbA1c<7% was higher for both oral (44–90%; dose-dependent) and s.c. (93%) semaglutide vs PBO (28%). Reductions in BW were greater with oral (2–7 kg) and s.c. (6 kg) semaglutide vs PBO (1 kg); with oral semaglutide they were dose-dependent and statistically significant vs PBO for doses ≥10 mg (p<0.0001). The proportion of patients achieving ≥5% weight loss was higher for both oral (21–71%) and s.c. (66%) semaglutide vs PBO (13%). Change in pulse ranged from –1.7 to 3.0 bpm with oral semaglutide, vs 2.6 bpm with s.c. semaglutide and –4.0 bpm with PBO. AEs were reported by 63–86% patients on oral semaglutide (trend for dose-dependency) vs 81% on s.c. semaglutide and 68% on PBO. Mild/moderate gastrointestinal (GI) AEs were most common; for oral semaglutide (dose dependent), s.c. semaglutide and PBO the proportion of patients with events was: nausea 13–37%, 32%, 1%; vomiting 6–24%, 9%, 4%; diarrhea 7–23%, 15%, 10%. Discontinuation due to AEs was more frequent with oral and s.c. semaglutide vs PBO, appeared dose-dependent and was mostly due to GI events. Pancreatitis was confirmed in 3 patients (1 with s.c. and 2 with oral semaglutide [20 and 40 mg]); none were serious AEs and all were mild/moderate in severity. Lipase levels (ratio to baseline) increased with oral (1.09–1.55) and s.c. (1.36) semaglutide vs PBO (0.99).

Conclusion Once-daily oral semaglutide improved glycemic control and BW in T2D. Oral semaglutide had no new safety or tolerability findings compared with s.c. semaglutide.

Disclosure: SJ: Consultant, Astra Zeneca, Consultant, Janssen Pharmaceuticals, Consultant, Eli Lilly & Company. TRP: Advisory Group Member, Novo Nordisk, Advisory Group Member, Eli Lilly & Company, Employee, CSO, Employee, CBmed - Center for Biomarker Research in Medicine, Researcher, Novo Nordisk, Speaker Bureau Member, Novo Nordisk. JR: Consultant, Janssen Pharmaceuticals, Consultant, Daiichi Sankyo, Researcher, GlaxoSmithKline, Consultant, Merck, Consultant, Sanofi, Consultant, Novo Nordisk, Consultant, Eli Lilly & Company, Advisory Group Member, Lexicon Pharmaceuticals, Inc., Researcher, Takeda, Advisory Group Member, Intarcia, Advisory Group Member, Boehringer Ingelheim, Advisory Group Member, Janssen Pharmaceuticals, Advisory Group Member, Daiichi Sankyo, Advisory Group Member, Merck, Researcher, Novartis Pharmaceuticals, Advisory Group Member, Sanofi, Advisory Group Member, Novo Nordisk, Researcher, Astra Zeneca, Advisory Group Member, Eli Lilly & Company, Consultant, Boehringer Ingelheim, Consultant, Intarcia, Consultant, Lexicon Pharmaceuticals, Inc., Researcher, Merck, Researcher, Pfizer, Inc., Researcher, Sanofi, Researcher, Novo Nordisk, Researcher, Eli Lilly & Company, Researcher, Bristol-Myers Squibb, Researcher, Hanmi, Researcher, Janssen Pharmaceuticals, Researcher, Daiichi Sankyo, Researcher, Asahi, Researcher, MannKind, Researcher, Boehringer Ingelheim, Researcher, Intarcia, Researcher, Lexicon Pharmaceuticals, Inc.. MLH: Employee, Novo Nordisk. OKHH: Employee, Novo Nordisk. MD: Advisory Group Member, Novo Nordisk, Advisory Group Member, Sanofi-Aventis, Advisory Group Member, Eli Lilly & Company, Advisory Group Member, Merck Sharp & Dohme, Advisory Group Member, Boehringer Ingelheim, Advisory Group Member, Astra Zeneca, Advisory Group Member, Janssen Pharmaceuticals, Board Member, Novo Nordisk, Board Member, Sanofi-Aventis, Board Member, Eli Lilly & Company, Board Member, Merck Sharp & Dohme, Board Member, Boehringer Ingelheim, Board Member, Astra Zeneca, Board Member, Janssen Pharmaceuticals, Board Member, Novo Nordisk, Board Member, Sanofi-Aventis, Board Member, Eli Lilly & Company, Board Member, Merck Sharp & Dohme, Board Member, Boehringer Ingelheim, Board Member, Astra Zeneca, Board Member, Janssen Pharmaceuticals, Researcher, Novo Nordisk, Researcher, Sanofi-Aventis, Researcher, Eli Lilly & Company, Speaker Bureau Member, Novo Nordisk, Speaker Bureau Member, Sanofi-Aventis, Speaker Bureau Member, Eli Lilly & Company, Speaker Bureau Member, Merck Sharp & Dohme, Speaker Bureau Member, Astra Zeneca, Speaker Bureau Member, Boehringer Ingelheim, Speaker Bureau Member, Astra Zeneca, Speaker Bureau Member, Janssen Pharmaceuticals, Speaker Bureau Member, Mitsubishi Tanabe Pharma Corporation, Consultant, Novo Nordisk, Consultant, Sanofi-Aventis, Consultant, Eli Lilly & Company, Consultant, Merck Sharp & Dohme, Consultant, Boehringer Ingelheim, Consultant, Astra Zeneca, Consultant, Janssen Pharmaceuticals.

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting/pr-resources-for-endo