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Document set current to 30 July 2026
Indication assessment · §2

Type 2 diabetes mellitus — evidence across compounds

Every compound the Institute assesses in type 2 diabetes mellitus, with its certainty rating.

Document identifier
CEI-IN-02/2
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

§2Evidence across compounds

Every compound the Institute assesses in this indication, with the effect as recorded, the certainty rating and the contributing trials. Effects are reported on the anchor outcome where the contributing trials measured it and on the outcome the trial actually reported where they did not.

Table 1. Compounds assessed in type 2 diabetes mellitus, ordered by certainty.

CompoundEffect as recordedInterval as reportedCertaintyTrials
DulaglutideGLP-1 receptor agonist, Fc-fusion protein−1.1 to −1.9 % HbA1c across the AWARD programme; 4.5 mg gave −1.9 % in AWARD-11AWARD-11 difference of 4.5 mg versus 1.5 mg −0.24 % (95 % CI −0.36 to −0.11)High5
ExenatideGLP-1 receptor agonist (exendin-based, short- and…−0.8 to −1.9 % HbA1c depending on presentation and background therapyDURATION-6 difference versus liraglutide +0.21 % (95 % CI 0.08 to 0.33), favouring liraglutideHigh3
LiraglutideGLP-1 receptor agonist (acylated, once-daily)−1.1 to −1.5 % HbA1c at 26 weeks with 1.8 mgLEAD-6 difference versus exenatide twice daily −0.33 % (95 % CI −0.47 to −0.18)High2
LixisenatideGLP-1 receptor agonist (exendin-based, short-acting)−0.7 to −0.9 % HbA1c at 24 weeks with pronounced postprandial glucose reductionGetGoal-M difference versus placebo −0.5 % (95 % CI −0.7 to −0.4)High3
SemaglutideGLP-1 receptor agonist (acylated, long-acting)−1.5 to −1.8 % HbA1c at 30–56 weeks versus placebo; superior to dulaglutide 1.5 mg in a head-to-head comparisonSUSTAIN 7 difference −0.41 % (95 % CI −0.57 to −0.25) for semaglutide 1.0 mg versus dulaglutide 1.5 mgHigh4
Semaglutide, oralGLP-1 receptor agonist, oral formulation with absorption…−1.2 to −1.4 % HbA1c at 26 weeks with 14 mg versus placeboPIONEER 1 estimated difference −1.1 % (95 % CI −1.3 to −0.9) for 14 mgHigh2
TirzepatideDual GIP and GLP-1 receptor agonist (acylated)−1.87 to −2.59 % HbA1c across doses and backgrounds; superior to semaglutide 1.0 mg, insulin degludec and insulin glargineSURPASS-2 difference versus semaglutide 1.0 mg −0.45 % (95 % CI −0.57 to −0.32) at 15 mgHigh5
CagriSema (cagrilintide with semaglutide)Fixed-ratio combination of a long-acting amylin analogue…−13.7 % body weight and −1.8 % HbA1c at 68 weeks in type 2 diabetesweight difference −10.4 percentage points (95 % CI −11.9 to −8.9)Moderate1
DanuglipronOral non-peptide GLP-1 receptor agonist−1.16 % HbA1c at 16 weeks with 120 mg twice daily versus placeboestimated difference −1.16 % (95 % CI −1.55 to −0.77)Moderate1
MazdutideDual glucagon and GLP-1 receptor agonist (oxyntomodulin…−1.8 % HbA1c at 24 weeks with 6 mgestimated difference −1.6 % (95 % CI −1.9 to −1.3)Moderate2
OrforglipronOral non-peptide GLP-1 receptor partial agonist−2.1 % HbA1c at 26 weeks with 45 mg versus −0.4 % with placeboestimated difference −1.7 % (95 % CI −2.1 to −1.3)Moderate3
PramlintideAmylin analogue, short-actingHbA1c −0.62 % versus −0.18 % with placebo at 52 weeks, with weight −1.4 kgestimated difference −0.44 % (95 % CI −0.63 to −0.25)Moderate1
RetatrutideTriple GIP, GLP-1 and glucagon receptor agonist (acylated)−2.02 % HbA1c at 36 weeks with 12 mg versus −0.01 % with placebo; weight −16.9 %estimated difference −2.02 % (95 % CI −2.45 to −1.59)Moderate2
CagrilintideLong-acting amylin and calcitonin receptor agonist…Combination with semaglutide 2.4 mg gave −15.6 % weight and −2.2 % HbA1c at 32 weeksphase 2; combination armLow1
Maridebart cafraglutideGIP receptor antagonist and GLP-1 receptor agonist…−2.2 % HbA1c reported at 52 weeks in phase 2phase 2Low1
SurvodutideDual glucagon and GLP-1 receptor agonist (acylated)−1.7 % HbA1c at 16 weeks in phase 2phase 2Low1
5-amino-1MQSmall-molecule nicotinamide N-methyltransferase inhibitorNo human trial identified—Very low0
EcnoglutideGLP-1 receptor agonist (cAMP-biased, acylated)−1.8 % HbA1c reported at 24 weeksreported without full confidence-interval disclosure in the sources available to the InstituteVery low1
MOTS-cMitochondrial-derived 16-residue peptideNo randomised controlled human trial identified—Very low0
Estimates in this table are not on a common scale and must not be subtracted from one another. Where a comparison between two compounds has been made directly, it appears in a synthesis and not here.
Compounds assessed in Type 2 diabetesPoint estimates with confidence intervals for each contributing study, plotted against the line of no effect.0.00.20.40.60.81.0Standardised direction and relative magnitudeCompoundEffect as recordedDulaglutideHigh certainty−1.1 to −1.9 % HbA1c across the…ExenatideHigh certainty−0.8 to −1.9 % HbA1c depending on…LiraglutideHigh certainty−1.1 to −1.5 % HbA1c at 26 weeks…LixisenatideHigh certainty−0.7 to −0.9 % HbA1c at 24 weeks…SemaglutideHigh certainty−1.5 to −1.8 % HbA1c at 30–56…Semaglutide, oralHigh certainty−1.2 to −1.4 % HbA1c at 26 weeks…TirzepatideHigh certainty−1.87 to −2.59 % HbA1c across…CagriSema (cagrilintid…Moderate certainty−13.7 % body weight and −1.8 %…DanuglipronModerate certainty−1.16 % HbA1c at 16 weeks with…MazdutideModerate certainty−1.8 % HbA1c at 24 weeks with 6 mgOrforglipronModerate certainty−2.1 % HbA1c at 26 weeks with 45…PramlintideModerate certaintyHbA1c −0.62 % versus −0.18 % with…
Moderate or high certaintyLow or very low certainty
Figure 1. Illustrative. Compounds assessed in this indication, plotted on a common standardised axis so that direction and relative magnitude can be compared at a glance. The estimates are not on a common natural scale and the intervals are the Institute's standardised representation of the reported precision rather than published confidence intervals.

§2.1Syntheses bearing on this indication

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
  2. Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. The Lancet Diabetes & Endocrinology 2018;6(4):275–286. doi:10.1016/S2213-8587(18)30024-X · PMID 29397376

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.

Compound Evidence Institute · CEI-IN-02/2 · https://compoundevidence.com/indications/t2dm/evidence/ · retrieved 30 July 2026
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