Semaglutide (Oral)

Drug Overview

Novo Nordisk’s semaglutide is an orally available GLP-1 agonist currently being investigated in Phase
III trials for the treatment of type 2 diabetes. GLP-1 agonists are incretin mimetics, mimicking the
endogenous gut hormone GLP-1, which stimulates insulin-secreting beta cells in the pancreas. This
triggers glucose-dependent insulin secretion, suppressing glucagon secretion, and thereby decreases
plasma glucose levels (Garber, 2012; Neumiller, 2009). GLP-1 agonists are associated with weight loss
and also delay gastric emptying, thus increasing satiety and suppressing appetite (Neumiller, 2009).

Analyst Outlook

Novo Nordisk is expected to position oral semaglutide as a glucagon-like peptide-1 (GLP-1) agonist to
be used in early lines of therapy by investigating lower doses of the drug in the Phase III PIONEER 3
trial, rather than attempting to compete directly with subcutaneous (SC) GLP-1 agonists at later lines.
The convenience and expected effectiveness of an oral GLP-1 agonist will allow oral semaglutide to
compete with dipeptidyl peptidase-IV (DPP-IV) inhibitors and sodium-glucose cotransporter-2 (SGLT-
2) inhibitors as a second- or third-line option for the treatment of type 2 diabetes. When used in high
doses, oral semaglutide has demonstrated equivalent effectiveness with subcutaneously injected GLP-
1 agonists in terms of glycated hemoglobin (HbA1c) reduction, though with significantly higher rates
of adverse effects.