Oral Semaglutide: A Review of the First Oral Glucagon-Like Peptide 1 Receptor Agonist

Aug 23, 2019Diabetes technology & therapeutics

Oral Semaglutide: Review of the First Pill That Mimics a Blood Sugar-Regulating Hormone

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Abstract

The oral formulation of semaglutide demonstrates similar efficacy to injectable GLP-1 receptor agonists in lowering hemoglobin A1c and facilitating weight loss.

Glucagon-like peptide 1 receptor agonists are effective in reducing hemoglobin A1c and promoting weight loss.
Four GLP-1 receptor agonists also show potential cardioprotective effects.
Subcutaneous administration has limited the use of these agents.
A new oral formulation of semaglutide uses sodium N-[8-(2-hydroxybenzoyl) amino caprylate] to enhance absorption.
The oral semaglutide was evaluated in PIONEER trials, showing comparable effectiveness to existing injectable options.
The PIONEER 6 trial indicates potential benefits on cardiovascular mortality, pending further confirmation from the SOUL trial.

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Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are highly effective at lowering hemoglobin A1c (HbA1c) and facilitating weight loss. Four agents in the GLP-1 RA class, albiglutide, liraglutide, dulaglutide, and semaglutide, also have cardioprotective effects. However, subcutaneous administration of these agents remains a major reason for their underutilization. A new coformulation of semaglutide with sodium N-[8-(2-hydroxybenzoyl) amino caprylate (SNAC) is the first oral GLP-1 RA reviewed by the U.S. Food and Drug Administration (FDA). The SNAC technology prevents destruction of semaglutide in the stomach and facilitates transcellular absorption through the gastric membrane enabling semaglutide to reach systemic circulation intact. The oral formulation of semaglutide was studied in the PIONEER trials, demonstrating similar efficacy to the presently available GLP-1 RAs with regard to HbA1c lowering and weight loss. Although the PIONEER 6 trial suggests positive effects on cardiovascular mortality with oral semaglutide, these benefits may not fully be appreciated until the completion of the SOUL trial.

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Oral Semaglutide: A Review of the First Oral Glucagon-Like Peptide 1 Receptor Agonist

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