Certainty index
Low certainty
Confidence in the effect estimate is limited. The true effect may be substantially different from the estimate.
Graded outcomes
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Table 1. Outcomes and syntheses graded at low certainty, on this page.
| Document | Type | Effect or conclusion as recorded |
|---|---|---|
| Semaglutide in prediabetes | Evidence extract | Reversion to normoglycaemia in 84.1 % of participants with prediabetes at baseline versus 47.8 % with placebo (STEP 1) |
| Semaglutide in lean-mass preservation | Evidence extract | Approximately 39 % of total mass lost was lean mass in the DXA substudy |
| Tirzepatide in mash | Evidence extract | Resolution of steatohepatitis without worsening fibrosis in 44–62 % across doses versus 10 % with placebo at 52 weeks |
| Tirzepatide in lean-mass preservation | Evidence extract | Approximately 25 % of total mass lost was lean mass in the body-composition substudy |
| Tirzepatide in knee osteoarthritis | Evidence extract | WOMAC pain score improvement exceeding placebo at 68 weeks |
| Retatrutide in mash | Evidence extract | Liver-fat reduction exceeding 80 % relative at higher doses in a phase 2 imaging substudy |
| Cagrilintide in type 2 diabetes | Evidence extract | Combination with semaglutide 2.4 mg gave −15.6 % weight and −2.2 % HbA1c at 32 weeks |
| Dulaglutide in chronic kidney disease | Evidence extract | Slower eGFR decline versus insulin glargine in moderate-to-severe chronic kidney disease |
| Danuglipron in obesity | Evidence extract | −8.0 to −13.0 % body weight at 32 weeks across doses, with discontinuation rates above 50 % in some arms |
| Survodutide in mash | Evidence extract | Histological improvement in fibrosis without worsening of steatohepatitis in 34.5 % at 4.8 mg versus 22.4 % with placebo at 48 weeks |
| Survodutide in type 2 diabetes | Evidence extract | −1.7 % HbA1c at 16 weeks in phase 2 |
| Ecnoglutide in obesity | Evidence extract | −13.2 % body weight at 48 weeks with the highest dose versus −0.5 % with placebo in a Chinese phase 3 trial |
| Petrelintide in obesity | Evidence extract | −8.6 % body weight at 16 weeks in a phase 1b multiple-ascending-dose study versus −1.7 % with placebo |
| Amycretin in obesity | Evidence extract | −13.1 % body weight at 12 weeks in a phase 1b subcutaneous study versus −1.1 % with placebo |
| Maridebart cafraglutide in obesity | Evidence extract | −16.2 % body weight at 52 weeks at the highest dose in phase 2 versus −2.5 % with placebo |
| Maridebart cafraglutide in type 2 diabetes | Evidence extract | −2.2 % HbA1c reported at 52 weeks in phase 2 |
| Pramlintide in obesity | Evidence extract | −3.7 kg at 16 weeks versus placebo in a non-diabetic obesity study |
| Tesamorelin in mash | Evidence extract | Liver fat fraction reduced by 4.1 percentage points versus 0.9 with placebo at 12 months in people with HIV and hepatic steatosis |
| CJC-1295 in gh axis | Evidence extract | Mean IGF-1 increased 1.5- to 3.0-fold above baseline and remained elevated for 6 to 11 days after a single dose in a phase 1 study of 11 participants |
| Ipamorelin in gh axis | Evidence extract | Dose-dependent growth-hormone release demonstrated in preclinical models and in early human study |
| Hexarelin in gh axis | Evidence extract | Marked acute growth-hormone release; the response attenuates substantially over 8 to 16 weeks of continuous administration |
| GHRP-6 in gh axis | Evidence extract | Dose-dependent acute growth-hormone release with attenuation on repeated administration |
| AOD-9604 in knee osteoarthritis | Evidence extract | A small trial in knee osteoarthritis reported no significant benefit on the primary endpoint |
| Thymosin beta-4 in wound healing | Evidence extract | Phase 2 trials in dry-eye disease, epidermolysis bullosa and venous stasis ulcers reported signals on some secondary endpoints without meeting primary endpoints consistently |
| GHK-Cu in wound healing | Evidence extract | Small controlled dermatological studies report improvements in skin roughness, wrinkle depth and collagen density with topical application over 12 weeks |
| LL-37 in wound healing | Evidence extract | A phase 1/2 trial of intralesional LL-37 in hard-to-heal venous leg ulcers reported greater ulcer-area reduction at intermediate doses than at the highest dose |
| SS-31 (elamipretide) in hfpef | Evidence extract | A phase 2 trial in heart failure with preserved ejection fraction did not demonstrate benefit on the primary endpoint |
| Glutathione in cognition | Evidence extract | Small randomised trials of intravenous and intranasal glutathione in Parkinson disease reported no significant benefit over placebo on motor endpoints |
| Kisspeptin-10 in pcos | Evidence extract | Kisspeptin-54 has been used as an oocyte-maturation trigger in assisted reproduction with reported reduction in ovarian hyperstimulation risk compared with human chorionic gonadotropin |
| Kisspeptin-10 in sexual dysfunction | Evidence extract | Small randomised crossover studies in men with hypoactive sexual desire reported changes in limbic activation on functional imaging and in behavioural measures |
| Change in lean mass during pharmacologically induced weight reduction | Synthesis | Low certainty evidence from body-composition sub-studies embedded in weight-loss trials indicates that the proportion of mass lost that is lean tissue in incretin-induced weight reduction ranges from… |
| Analytical surveys of unregulated peptide supply | Synthesis | Low certainty evidence from a small number of analytical surveys indicates that identity is usually confirmed for the principal high-volume compounds and that content against label claim is more… |
| Percentage weight change as a surrogate outcome | Synthesis | Low certainty evidence indicates that percentage weight change is an imperfect surrogate. The Institute records two observations that constrain the inference in opposite directions: within the… |
| The rodent thyroid C-cell signal and its human relevance | Synthesis | Low certainty evidence bears on this question. The rodent finding that motivates the boxed warning is reproducible and dose-dependent; the density of glucagon-like peptide-1 receptors on rodent… |
| Delayed gastric emptying, residual gastric content and procedural sedation | Synthesis | Low certainty evidence, almost entirely observational, indicates that residual gastric content is found more often in treated patients after a standard fasting period. Pulmonary aspiration is rare… |
| Bacterial endotoxin in research-supply peptide presentations | Synthesis | Low certainty evidence bears on this question because almost no data exist. Endotoxin was reported on none of the certificates in the Institute’s sampled set. The Institute records that endotoxin is… |
| Melanocortin receptor agonists: approved indications and supplied uses | Synthesis | Low certainty evidence bears on the supplied uses. One compound in this group holds an approval on the basis of two randomised trials reporting a statistically significant but numerically small… |
| Mitochondria-targeted peptides in bioenergetic disorders | Synthesis | Low certainty evidence describes this field. A crossover phase 2 trial in a small sample reported an increase in six-minute walk distance; the subsequent adequately powered phase 3 trial did not meet… |
| Thymic peptides in infection and immune support | Synthesis | Low certainty evidence supports a modest effect of thymosin alpha-1 in chronic viral hepatitis in an era of therapy now superseded, and a single-country mortality signal in severe sepsis that has not… |
| Distribution of access to obesity pharmacotherapy | Synthesis | Low certainty evidence indicates that eligibility under the pivotal trial criteria substantially exceeds treated prevalence in every jurisdiction for which the Institute could obtain data, and that… |
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