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
Certainty index

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.

Graded outcomes

62 documents · page 1 of 2

Table 1. Outcomes and syntheses graded at high certainty, on this page.

DocumentTypeEffect or conclusion as recorded
Semaglutide in obesityEvidence extract−14.9 % body weight at 68 weeks with semaglutide 2.4 mg versus −2.4 % with placebo
Semaglutide in type 2 diabetesEvidence extract−1.5 to −1.8 % HbA1c at 30–56 weeks versus placebo; superior to dulaglutide 1.5 mg in a head-to-head comparison
Semaglutide in cardiovascularEvidence extractThree-point MACE hazard ratio 0.80 in adults with overweight or obesity and established cardiovascular disease without diabetes
Semaglutide in chronic kidney diseaseEvidence extractComposite kidney outcome hazard ratio 0.76 in type 2 diabetes with chronic kidney disease
Semaglutide, oral in type 2 diabetesEvidence extract−1.2 to −1.4 % HbA1c at 26 weeks with 14 mg versus placebo
Tirzepatide in obesityEvidence extract−20.9 % body weight at 72 weeks with 15 mg versus −3.1 % with placebo (SURMOUNT-1)
Tirzepatide in type 2 diabetesEvidence extract−1.87 to −2.59 % HbA1c across doses and backgrounds; superior to semaglutide 1.0 mg, insulin degludec and insulin glargine
Tirzepatide in sleep apnoeaEvidence extractApnoea–hypopnoea index reduced by 25.3 events/hour versus 5.3 with placebo in participants not using positive airway pressure
Liraglutide in obesityEvidence extract−8.0 % body weight at 56 weeks with 3.0 mg versus −2.6 % with placebo
Liraglutide in type 2 diabetesEvidence extract−1.1 to −1.5 % HbA1c at 26 weeks with 1.8 mg
Liraglutide in cardiovascularEvidence extractMACE hazard ratio 0.87 in type 2 diabetes at high cardiovascular risk
Dulaglutide in type 2 diabetesEvidence extract−1.1 to −1.9 % HbA1c across the AWARD programme; 4.5 mg gave −1.9 % in AWARD-11
Dulaglutide in cardiovascularEvidence extractMACE hazard ratio 0.88 in a population with a majority without established cardiovascular disease
Exenatide in type 2 diabetesEvidence extract−0.8 to −1.9 % HbA1c depending on presentation and background therapy
Exenatide in cardiovascularEvidence extractMACE hazard ratio 0.91 — non-inferior to placebo but not superior
Lixisenatide in type 2 diabetesEvidence extract−0.7 to −0.9 % HbA1c at 24 weeks with pronounced postprandial glucose reduction
Lixisenatide in cardiovascularEvidence extractMACE hazard ratio 1.02 — neutral
Glucagon-like peptide-1 receptor agonists for weight reduction in adults with obesitySynthesisHigh certainty evidence indicates that glucagon-like peptide-1 receptor agonists reduce body weight substantially more than placebo over 56 to 104 weeks, with a placebo-subtracted effect that differs…
Cardiovascular outcomes with glucagon-like peptide-1 receptor agonistsSynthesisHigh certainty evidence indicates that the class as a whole reduces major adverse cardiovascular events relative to placebo in the enrolled populations. The Institute nonetheless declines to describe…
Gastrointestinal adverse events with incretin receptor agonistsSynthesisHigh certainty evidence indicates that nausea, vomiting, diarrhoea and constipation are substantially more frequent with incretin receptor agonists than with placebo, that they are dose- and…
Kidney outcomes with incretin receptor agonists in chronic kidney diseaseSynthesisHigh certainty evidence from one dedicated event-driven trial, supported by kidney outcomes collected within cardiovascular outcome trials, indicates a reduction in the composite kidney outcome. The…
Counter-ion content and its effect on delivered peptide massSynthesisHigh certainty evidence, in this case arising from the arithmetic of mass balance rather than from clinical study, establishes that a trifluoroacetate salt of a basic peptide can carry a counter-ion…
Tirzepatide compared with semaglutide in type 2 diabetesSynthesisHigh certainty evidence from one adequately powered double-blind head-to-head trial indicates greater glycaemic and weight effect with tirzepatide at all three doses. The Institute records the…
Dependence of reported purity on the analytical methodSynthesisHigh certainty evidence, again analytical rather than clinical, establishes that the same material can yield materially different area-percentage purity figures under different gradients, at…
Tirzepatide in obesity and overweight in adults: effect on the anchor outcomeSynthesisHigh certainty evidence from 9 contributing trials bears on the effect of Tirzepatide on the anchor outcome for obesity and overweight in adults. The estimate the Institute carries in the monograph…
Semaglutide in obesity and overweight in adults: effect on the anchor outcomeSynthesisHigh certainty evidence from 8 contributing trials bears on the effect of Semaglutide on the anchor outcome for obesity and overweight in adults. The estimate the Institute carries in the monograph…
Dulaglutide in type 2 diabetes mellitus: effect on the anchor outcomeSynthesisHigh certainty evidence from 7 contributing trials bears on the effect of Dulaglutide on the anchor outcome for type 2 diabetes mellitus. The estimate the Institute carries in the monograph is: −1.1…
Semaglutide in type 2 diabetes mellitus: effect on the anchor outcomeSynthesisHigh certainty evidence from 7 contributing trials bears on the effect of Semaglutide on the anchor outcome for type 2 diabetes mellitus. The estimate the Institute carries in the monograph is: −1.5…
Tirzepatide in type 2 diabetes mellitus: effect on the anchor outcomeSynthesisHigh certainty evidence from 7 contributing trials bears on the effect of Tirzepatide on the anchor outcome for type 2 diabetes mellitus. The estimate the Institute carries in the monograph is: −1.87…
Exenatide in type 2 diabetes mellitus: effect on the anchor outcomeSynthesisHigh certainty evidence from 5 contributing trials bears on the effect of Exenatide on the anchor outcome for type 2 diabetes mellitus. The estimate the Institute carries in the monograph is: −0.8 to…
Lixisenatide in type 2 diabetes mellitus: effect on the anchor outcomeSynthesisHigh certainty evidence from 4 contributing trials bears on the effect of Lixisenatide on the anchor outcome for type 2 diabetes mellitus. The estimate the Institute carries in the monograph is: −0.7…
Exenatide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: effect on the anchor…SynthesisHigh certainty evidence from 3 contributing trials bears on the effect of Exenatide on the anchor outcome for atherosclerotic cardiovascular disease and cardiovascular risk reduction. The estimate…
Liraglutide in obesity and overweight in adults: effect on the anchor outcomeSynthesisHigh certainty evidence from 3 contributing trials bears on the effect of Liraglutide on the anchor outcome for obesity and overweight in adults. The estimate the Institute carries in the monograph…
Semaglutide, oral in type 2 diabetes mellitus: effect on the anchor outcomeSynthesisHigh certainty evidence from 3 contributing trials bears on the effect of Semaglutide, oral on the anchor outcome for type 2 diabetes mellitus. The estimate the Institute carries in the monograph is…
Dulaglutide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: effect on the anchor…SynthesisHigh certainty evidence from 2 contributing trials bears on the effect of Dulaglutide on the anchor outcome for atherosclerotic cardiovascular disease and cardiovascular risk reduction. The estimate…
Liraglutide in type 2 diabetes mellitus: effect on the anchor outcomeSynthesisHigh certainty evidence from 2 contributing trials bears on the effect of Liraglutide on the anchor outcome for type 2 diabetes mellitus. The estimate the Institute carries in the monograph is: −1.1…
Semaglutide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: effect on the anchor…SynthesisHigh certainty evidence from 2 contributing trials bears on the effect of Semaglutide on the anchor outcome for atherosclerotic cardiovascular disease and cardiovascular risk reduction. The estimate…
Tirzepatide in obstructive sleep apnoea with obesity: effect on the anchor outcomeSynthesisHigh certainty evidence from 2 contributing trials bears on the effect of Tirzepatide on the anchor outcome for obstructive sleep apnoea with obesity. The estimate the Institute carries in the…
Tirzepatide in obesity and overweight in adults: tolerability and discontinuationSynthesisHigh certainty evidence from 9 contributing trials bears on tolerability. Discontinuation for adverse events is reported in the summary-of-findings table alongside the efficacy outcomes rather than…
Semaglutide in obesity and overweight in adults: tolerability and discontinuationSynthesisHigh certainty evidence from 8 contributing trials bears on tolerability. Discontinuation for adverse events is reported in the summary-of-findings table alongside the efficacy outcomes rather than…

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