Independent · non-commercial · publishes on a quarterly cycle|Current cycle 2026 Q3
Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Compound monograph · Incretin receptor agonists

Semaglutide, oral — compound monograph

GLP-1 receptor agonist, oral formulation with absorption enhancer. Approved. The Institute assesses 3 outcomes for this compound and grades the strongest at high certainty.

Document identifier
CEI-MN-002
Series
Compound monograph
Version
1.0
Published
28 Aug 2023
Last reviewed
28 Jun 2024
Next review
28 Jun 2026
Identifier
10.71829/cei.mono.2
Certainty
High
Cycle
2023 Q3

§1Identification and status

§1.1Nomenclature

Preferred name
Semaglutide, oral
Compound class
GLP-1 receptor agonist, oral formulation with absorption enhancer
Assessment series
Incretin receptor agonists
Synonyms and codes
NN9924 · oral semaglutide · Rybelsus (trade) · semaglutide with SNAC
Route as evaluated
Oral once daily, fasted, with no more than 120 mL of water and at least 30 minutes before other intake

§1.2Chemistry

Chemical identifiers are reproduced where they are public. Where a structure has not been published the monograph records not disclosed rather than constructing one.[1]

CAS registry number
910463-68-2 (active moiety)
Molecular formula
C187H291N45O59 (active moiety)
Average mass
4113.58
Monoisotopic mass
4111.10
ATC classification
A10BJ06

§1.3Sequence and structural notes

Identical to subcutaneous semaglutide; co-formulated with 300 mg sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC)

The peptide is unchanged. SNAC raises local gastric pH and transiently increases transcellular permeability in a small region of gastric mucosa, allowing absorption of an intact 4 kDa peptide at low but reproducible efficiency.

§1.4Assessment status

The Institute assesses Semaglutide, oral across 3 indications and grades the strongest of them at high certainty. Holds a marketing authorisation for at least one indication in at least one jurisdiction.

Distribution of certainty ratingsShare of assessed outcomes at each certainty level.3assessed outcomes
HighModerateLowVery low
Figure 1. Distribution of certainty ratings across the 3 outcomes the Institute assesses for Semaglutide, oral. A rating attaches to a specific population, comparator and outcome and does not transfer between them.

Table 1. Assessed outcomes for Semaglutide, oral, ordered by certainty. Each row links to the per-indication evidence extract.

IndicationEffect as recordedCertaintyTrials
Type 2 diabetes mellitus−1.2 to −1.4 % HbA1c at 26 weeks with 14 mg versus placeboHigh2
Atherosclerotic cardiovascular disease and cardiovascular risk reductionMACE hazard ratio 0.79 (non-inferiority design) in PIONEER 6; 0.86 in the event-driven SOUL trialModerate2
Obesity and overweight in adults−15.1 % body weight with oral 50 mg at 68 weeks versus −2.4 % with placeboModerate1
Effects are reproduced as the contributing trials reported them. Where a confidence interval is held it appears on the per-indication extract rather than in this summary table.

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

  1. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products. ICH Harmonised Tripartite Guideline 1999;Step 4 version. identifier not held by the Institute

Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.

Nothing published by the Institute is medical advice, a diagnosis, a prescription, a treatment recommendation or a purchasing recommendation. Compounds supplied for research use are not approved for human or veterinary use in any jurisdiction, and a favourable analytical assessment of a supplier is not a statement that any product is safe or effective. The Institute publishes certainty ratings and never recommendations. No telephone number, messaging handle or ordering channel appears anywhere on this site.