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Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Indication assessment · §4

Type 2 diabetes mellitus — compounds assessed

The 19 compounds the Institute assesses in type 2 diabetes mellitus.

Document identifier
CEI-IN-02/4
Series
Indication assessment
Version
2.0
Published
28 Apr 2024
Last reviewed
28 Apr 2024
Next review
28 Apr 2026
Identifier
10.71829/cei.ind.2
Certainty
Not rated
Cycle
2024 Q2
ICD-11
5A11
Category
Metabolic

§4Compounds assessed

Compounds the Institute assesses in this indication, with the class of each and its overall certainty. A compound appears here whether or not the evidence supports its use, because recording that a compound has been studied and found wanting is as much part of the assessment as recording that one has not.

  • GLP-1 receptor agonist, Fc-fusion protein5 contributing trialsfull monograph

    −1.1 to −1.9 % HbA1c across the AWARD programme; 4.5 mg gave −1.9 % in AWARD-11 — Eleven-trial programme with active comparators.

    High
  • GLP-1 receptor agonist (exendin-based, short- and extended-release)3 contributing trialsfull monograph

    −0.8 to −1.9 % HbA1c depending on presentation and background therapy — Long clinical record; the extended-release presentation is superior to the immediate-release one for HbA1c.

    High
  • GLP-1 receptor agonist (acylated, once-daily)2 contributing trialsfull monograph

    −1.1 to −1.5 % HbA1c at 26 weeks with 1.8 mg — Large and reproducible.

    High
  • GLP-1 receptor agonist (exendin-based, short-acting)3 contributing trialsfull monograph

    −0.7 to −0.9 % HbA1c at 24 weeks with pronounced postprandial glucose reduction — Smaller HbA1c effect than the long-acting agents, with a distinctly different postprandial profile.

    High
  • GLP-1 receptor agonist (acylated, long-acting)4 contributing trialsfull monograph

    −1.5 to −1.8 % HbA1c at 30–56 weeks versus placebo; superior to dulaglutide 1.5 mg in a head-to-head comparison — Dose-dependent, reproducible across background therapies.

    High
  • GLP-1 receptor agonist, oral formulation with absorption enhancer2 contributing trialsfull monograph

    −1.2 to −1.4 % HbA1c at 26 weeks with 14 mg versus placebo — Ten-trial phase 3 programme with consistent dose-response.

    High
  • Dual GIP and GLP-1 receptor agonist (acylated)5 contributing trialsfull monograph

    −1.87 to −2.59 % HbA1c across doses and backgrounds; superior to semaglutide 1.0 mg, insulin degludec and insulin glargine — Five-trial programme with active comparators throughout, an unusually strong design feature.

    High
  • Fixed-ratio combination of a long-acting amylin analogue and a GLP-1 receptor agonist1 contributing trialfull monograph

    −13.7 % body weight and −1.8 % HbA1c at 68 weeks in type 2 diabetes — Attenuated weight effect in diabetes, consistent with the pattern seen across the incretin class.

    Moderate
  • Oral non-peptide GLP-1 receptor agonist1 contributing trialfull monograph

    −1.16 % HbA1c at 16 weeks with 120 mg twice daily versus placebo — Phase 2b; efficacy was established but did not exceed the injectable class.

    Moderate
  • Dual glucagon and GLP-1 receptor agonist (oxyntomodulin analogue)2 contributing trialsfull monograph

    −1.8 % HbA1c at 24 weeks with 6 mg — Phase 3 in a Chinese population.

    Moderate
  • Oral non-peptide GLP-1 receptor partial agonist3 contributing trialsfull monograph

    −2.1 % HbA1c at 26 weeks with 45 mg versus −0.4 % with placebo — Phase 2 dose-response with a clear gradient.

    Moderate
  • Amylin analogue, short-acting1 contributing trialfull monograph

    HbA1c −0.62 % versus −0.18 % with placebo at 52 weeks, with weight −1.4 kg — Insulin-treated type 2 diabetes.

    Moderate
  • Triple GIP, GLP-1 and glucagon receptor agonist (acylated)2 contributing trialsfull monograph

    −2.02 % HbA1c at 36 weeks with 12 mg versus −0.01 % with placebo; weight −16.9 % — Phase 2, active- and placebo-controlled with dulaglutide 1.5 mg as reference.

    Moderate
  • Long-acting amylin and calcitonin receptor agonist (acylated)1 contributing trialfull monograph

    Combination with semaglutide 2.4 mg gave −15.6 % weight and −2.2 % HbA1c at 32 weeks — Attribution of effect between components is not resolvable from the reported design.

    Low
  • GIP receptor antagonist and GLP-1 receptor agonist conjugate (antibody–peptide)1 contributing trialfull monograph

    −2.2 % HbA1c reported at 52 weeks in phase 2 — Small sample.

    Low
  • Dual glucagon and GLP-1 receptor agonist (acylated)1 contributing trialfull monograph

    −1.7 % HbA1c at 16 weeks in phase 2 — Short duration; the cardiovascular outcome trial was recruiting at this cycle.

    Low
  • Small-molecule nicotinamide N-methyltransferase inhibitor0 contributing trialsfull monograph

    No human trial identified — —

    Very low
  • GLP-1 receptor agonist (cAMP-biased, acylated)1 contributing trialfull monograph

    −1.8 % HbA1c reported at 24 weeks — Reporting incompleteness is itself the reason for the rating.

    Very low
  • Mitochondrial-derived 16-residue peptide0 contributing trialsfull monograph

    No randomised controlled human trial identified — Rodent insulin-sensitivity findings only.

    Very low

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. Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Rydén L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet 2019;394(10193):121–130. doi:10.1016/S0140-6736(19)31149-3 · PMID 31189511

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