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Compound monograph · evidence extract

Semaglutide, oral in type 2 diabetes mellitus — evidence extract

The Institute's graded assessment of Semaglutide, oral for type 2 diabetes mellitus, with the contributing trials and the domain-by-domain certainty reasoning.

Document identifier
CEI-MN-002/EV-T2DM
Series
Evidence extract
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

§1Evidence extract: Type 2 diabetes mellitus

§1.1Question and anchor outcome

Population
A disorder of glucose regulation characterised by insulin resistance with relative insulin deficiency, diagnosed by glycated haemoglobin, fasting plasma glucose or oral glucose tolerance criteria.
Intervention
Semaglutide, oral, oral once daily, fasted, with no more than 120 ml of water and at least 30 minutes before other intake
Comparator
As used in each contributing trial; reported per trial rather than pooled across comparator types
Anchor outcome
Change in HbA1c (%, mmol/mol)

Additional outcomes the Institute extracts for this indication: Proportion achieving HbA1c <7.0 % and ≤6.5 %; Change in fasting serum glucose; Change in body weight; Documented symptomatic hypoglycaemia.

§1.2Contributing trials

Table 1. Trials contributing to the assessment of Semaglutide, oral in type 2 diabetes mellitus.

TrialPhaseDesignRandomisedDurationYear
PIONEER-13Randomised, double-blind, placebo-controlled70326 weeks2019
PIONEER-63Event-driven cardiovascular outcome trial3,183Median 15.9 months2019

§1.3Certainty assessment

Certainty assessment by domainDowngrading decision recorded for each certainty domain.Certainty domainNo concernSeriousVery seriousEffect on ratingRisk of biasno downgradeInconsistencyno downgradeIndirectnessno downgradeImprecisionno downgradePublication biasno downgradeTotal downgrading: 0 levelsHigh certainty
Figure 2. Domain-by-domain certainty assessment for Semaglutide, oral in type 2 diabetes mellitus. The starting rating for a body of randomised evidence is high; each serious concern reduces it by one level and each very serious concern by two.

Table 2. Reasoning recorded against each certainty domain.

DomainRatingReasoning
Risk of biasNo concernNo serious concern identified in this domain.
InconsistencyNo concernNo serious concern identified in this domain.
IndirectnessNo concernNo serious concern identified in this domain.
ImprecisionNo concernNo serious concern identified in this domain.
Publication biasNo concernNo serious concern identified in this domain.
Overall rating: High certainty. The Institute is confident that the true effect lies close to the estimate. Further research is very unlikely to change confidence in the estimate.

§1.4What this extract does not establish

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. Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, Jeppesen OK, Lingvay I, Mosenzon O, Pedersen SD, Tack CJ, Thomsen M, Vilsbøll T, Warren ML, Bain SC. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. New England Journal of Medicine 2019;381(9):841–851. doi:10.1056/NEJMoa1901118 · PMID 31185157
  2. Aroda VR, Rosenstock J, Terauchi Y, Altuntas Y, Lalic NM, Morales Villegas EC, Jeppesen OK, Christiansen E, Hertz CL, Haluzík M. PIONEER 1: randomized clinical trial of the efficacy and safety of oral semaglutide monotherapy in comparison with placebo in patients with type 2 diabetes. Diabetes Care 2019;42(9):1724–1732. doi:10.2337/dc19-0749 · PMID 31186300
  3. Knop FK, Aroda VR, do Vale RD, Holst-Hansen T, Laursen PN, Rosenstock J, Rubino DM, Garvey WT. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet 2023;402(10403):705–719. doi:10.1016/S0140-6736(23)01185-6 · PMID 37364590

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