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

Moderate certainty — page 2

The true effect is likely to be close to the estimate, but there is a possibility that it is substantially different. Further research is likely to have an important impact on confidence in the estimate.

Graded outcomes

114 documents · page 2 of 3

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

DocumentTypeEffect or conclusion as recorded
SS-31 (elamipretide) in mitochondrial diseaseEvidence extractA phase 3 trial in primary mitochondrial myopathy did not meet its primary endpoints of six-minute walk distance and symptom score at 24 weeks
SS-31 (elamipretide) in cardiovascularEvidence extractA phase 2 trial in ST-elevation myocardial infarction did not reduce infarct size
PT-141 (bremelanotide) in sexual dysfunctionEvidence extractChange in Female Sexual Function Index desire domain of +0.30 versus +0.06 with placebo, and improvement in the Female Sexual Distress Scale item 13 of −0.73 versus −0.41
Kisspeptin-10 in gh axisEvidence extractDiagnostic use as a probe of hypothalamic-pituitary-gonadal function
Gonadorelin in gh axisEvidence extractA luteinising hormone rise after gonadorelin distinguishes pituitary from hypothalamic causes of hypogonadotropic hypogonadism
Gonadorelin in pcosEvidence extractPulsatile administration by pump induces ovulation in hypothalamic amenorrhoea with reported ovulation rates above 80 % per cycle in selected patients
Dual and triple incretin receptor agonists compared with single glucagon-like peptide-1 receptor agonists for…SynthesisModerate certainty evidence indicates that multi-receptor agonists produce a larger mean weight reduction than single glucagon-like peptide-1 receptor agonists. One head-to-head trial supports the…
Weight change after discontinuation of an incretin receptor agonistSynthesisModerate certainty evidence from two randomised withdrawal trials indicates that a substantial proportion of the weight lost during treatment is regained after withdrawal, and that continued…
Oral compared with injectable presentations of glucagon-like peptide-1 receptor agonismSynthesisModerate certainty evidence indicates that oral presentations can achieve efficacy in the range of injectable glucagon-like peptide-1 receptor agonists when sufficient doses are achieved, and that…
Incretin receptor agonists in heart failure with preserved ejection fraction and obesitySynthesisModerate certainty evidence indicates an improvement in symptom scores and in six-minute walk distance, and one trial reports a reduction in a composite of cardiovascular death and worsening heart…
Incretin receptor agonists for metabolic dysfunction-associated steatohepatitisSynthesisModerate certainty evidence indicates that incretin receptor agonists produce resolution of steatohepatitis without worsening of fibrosis substantially more often than placebo at 48 to 72 weeks…
Weight-reducing agents for obstructive sleep apnoeaSynthesisModerate certainty evidence indicates a clinically meaningful reduction in the apnoea–hypopnoea index. The Institute records that the apnoea–hypopnoea index is itself a surrogate: no contributing…
Completeness of certificates of analysis in the research-supply channelSynthesisModerate certainty evidence from the Institute’s own assessment of the twenty suppliers in its set indicates that a purity percentage is almost always present, that the method producing it is named…
The consequences of a wholly sponsor-generated evidence baseSynthesisModerate certainty methodological evidence indicates that industry-sponsored trials report more favourable efficacy conclusions and less complete harms data than independently conducted trials of the…
Incretin receptor agonists in adolescentsSynthesisModerate certainty evidence indicates a substantial reduction in body-mass index over 56 to 68 weeks, larger in absolute terms than that observed in adults for the same agent. The Institute…
Amylin analogues as monotherapy and in combinationSynthesisModerate certainty evidence indicates that a long-acting amylin analogue produces a weight reduction of roughly 8 to 11 % as monotherapy and that the fixed combination with semaglutide exceeds either…
Discontinued development programmes as evidenceSynthesisModerate certainty evidence supports the position that a discontinued programme is informative and is frequently the most informative evidence available for a compound. A programme discontinued for…
Reconstitution practice and delivered doseSynthesisModerate certainty evidence, principally analytical rather than clinical, indicates that three distinct errors compound in ordinary reconstitution practice: the labelled mass overstates peptide…
Acute pancreatitis with incretin-based therapiesSynthesisModerate certainty evidence from the pooled cardiovascular outcome trials, in which pancreatitis was adjudicated and exposure was long, does not indicate a materially increased incidence…
Cardiovascular benefit in primary compared with secondary preventionSynthesisModerate certainty evidence, resting principally on one trial that enrolled a majority primary-prevention population, indicates that the relative effect is broadly similar across strata. The…
In-use stability of reconstituted peptide solutionsSynthesisModerate certainty evidence, drawn from the formulation-science literature rather than from product-specific studies, indicates that freeze–thaw cycling of an unbuffered or phosphate-buffered peptide…
Transitivity in the incretin networkSynthesisModerate certainty evidence indicates that the transitivity assumption is only partially satisfied. Primary analysis timepoints range from 36 to 104 weeks; background lifestyle intervention ranges…
Retatrutide in obesity and overweight in adults: effect on the anchor outcomeSynthesisModerate certainty evidence from 5 contributing trials bears on the effect of Retatrutide on the anchor outcome for obesity and overweight in adults. The estimate the Institute carries in the…
CagriSema (cagrilintide with semaglutide) in obesity and overweight in adults: effect on the anchor outcomeSynthesisModerate certainty evidence from 4 contributing trials bears on the effect of CagriSema (cagrilintide with semaglutide) on the anchor outcome for obesity and overweight in adults. The estimate the…
Orforglipron in type 2 diabetes mellitus: effect on the anchor outcomeSynthesisModerate certainty evidence from 4 contributing trials bears on the effect of Orforglipron on the anchor outcome for type 2 diabetes mellitus. The estimate the Institute carries in the monograph is…
Survodutide in obesity and overweight in adults: effect on the anchor outcomeSynthesisModerate certainty evidence from 4 contributing trials bears on the effect of Survodutide on the anchor outcome for obesity and overweight in adults. The estimate the Institute carries in the…
Thymosin alpha-1 in immune modulation and adjunctive immunotherapy: effect on the anchor outcomeSynthesisModerate certainty evidence from 4 contributing trials bears on the effect of Thymosin alpha-1 on the anchor outcome for immune modulation and adjunctive immunotherapy. The estimate the Institute…
Mazdutide in obesity and overweight in adults: effect on the anchor outcomeSynthesisModerate certainty evidence from 3 contributing trials bears on the effect of Mazdutide on the anchor outcome for obesity and overweight in adults. The estimate the Institute carries in the monograph…
Mazdutide in type 2 diabetes mellitus: effect on the anchor outcomeSynthesisModerate certainty evidence from 3 contributing trials bears on the effect of Mazdutide on the anchor outcome for type 2 diabetes mellitus. The estimate the Institute carries in the monograph is…
Orforglipron in obesity and overweight in adults: effect on the anchor outcomeSynthesisModerate certainty evidence from 3 contributing trials bears on the effect of Orforglipron on the anchor outcome for obesity and overweight in adults. The estimate the Institute carries in the…
Teduglutide in inflammatory bowel disease and mucosal barrier disorders: effect on the anchor outcomeSynthesisModerate certainty evidence from 3 contributing trials bears on the effect of Teduglutide on the anchor outcome for inflammatory bowel disease and mucosal barrier disorders. The estimate the…
CagriSema (cagrilintide with semaglutide) in type 2 diabetes mellitus: effect on the anchor outcomeSynthesisModerate certainty evidence from 2 contributing trials bears on the effect of CagriSema (cagrilintide with semaglutide) on the anchor outcome for type 2 diabetes mellitus. The estimate the Institute…
Gonadorelin in growth hormone deficiency and growth-hormone secretagogue pharmacology: effect on the anchor…SynthesisModerate certainty evidence from 2 contributing trials bears on the effect of Gonadorelin on the anchor outcome for growth hormone deficiency and growth-hormone secretagogue pharmacology. The…
Kisspeptin-10 in growth hormone deficiency and growth-hormone secretagogue pharmacology: effect on the anchor…SynthesisModerate certainty evidence from 2 contributing trials bears on the effect of Kisspeptin-10 on the anchor outcome for growth hormone deficiency and growth-hormone secretagogue pharmacology. The…
Larazotide acetate in inflammatory bowel disease and mucosal barrier disorders: effect on the anchor outcomeSynthesisModerate certainty evidence from 2 contributing trials bears on the effect of Larazotide acetate on the anchor outcome for inflammatory bowel disease and mucosal barrier disorders. The estimate the…
Liraglutide in adjunctive therapy in type 1 diabetes: effect on the anchor outcomeSynthesisModerate certainty evidence from 2 contributing trials bears on the effect of Liraglutide on the anchor outcome for adjunctive therapy in type 1 diabetes. The estimate the Institute carries in the…
Semaglutide, oral in atherosclerotic cardiovascular disease and cardiovascular risk reduction: effect on the…SynthesisModerate certainty evidence from 2 contributing trials bears on the effect of Semaglutide, oral on the anchor outcome for atherosclerotic cardiovascular disease and cardiovascular risk reduction. The…
PT-141 (bremelanotide) in hypoactive sexual desire and erectile dysfunction: effect on the anchor outcomeSynthesisModerate certainty evidence from 2 contributing trials bears on the effect of PT-141 (bremelanotide) on the anchor outcome for hypoactive sexual desire and erectile dysfunction. The estimate the…
Retatrutide in type 2 diabetes mellitus: effect on the anchor outcomeSynthesisModerate certainty evidence from 2 contributing trials bears on the effect of Retatrutide on the anchor outcome for type 2 diabetes mellitus. The estimate the Institute carries in the monograph is…
Semaglutide in heart failure with preserved ejection fraction and obesity: effect on the anchor outcomeSynthesisModerate certainty evidence from 2 contributing trials bears on the effect of Semaglutide on the anchor outcome for heart failure with preserved ejection fraction and obesity. The estimate the…

page 2 of 3

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.