Evidence Log
Ratings change. Here's the receipt.
A registry that never revises anything isn't following evidence — it's defending a position. Every change to an evidence level is logged with the reason behind it.
Evidence Watch
The evidence changes. We’ll tell you when it actually matters.
Major trial result. Regulatory change. Evidence rating moved. That’s the sort of thing we’ll send — no daily noise, no supplier promotions.
Evidence-level changes
These entries record changes to our rating of the evidence. A rating going up means better or more research now exists — not that the compound became stronger or safer. Evidence levels (L0-L5) describe the strongest type of study available, not a star rating.
- L4Good human trials
Added peer-reviewed SYNCHRONIZE-2 Phase 3 results in adults with obesity or overweight and type 2 diabetes. The NEJM treatment-regimen estimand showed mean weight changes of -8.2% (3.6 mg) and -9.8% (6.0 mg) versus -3.9% placebo at 76 weeks; sponsor-reported efficacy-estimand results reached up to -13.1% versus -3.1%.
The new Phase 3 publication materially strengthens the human evidence base but does not justify L5: survodutide remains investigational, the wider Phase 3 programme and long-term outcomes are incomplete, and gastrointestinal tolerability/discontinuation remains a material limitation. Estimands are labelled separately to avoid presenting efficacy-estimand results as the primary treatment-regimen result.
- L4Good human trials
Added CBL-514, an investigational small-molecule injection (not a peptide), with peer-reviewed Phase 2 and Phase 2b abdominal subcutaneous fat-reduction results, the September 2026 Phase 3 SUPREME-01 start, the tirzepatide combination IND and sponsor-reported Dercum's disease Phase 2 results.
Added at L4 for treated-area abdominal fat reduction only, based on completed controlled Phase 2/2b trials. Phase 3 initiation does not raise the grade. Local fat reduction is not obesity treatment; weight-regain and Dercum's findings remain investigational or sponsor-reported. Reviewed 3 October 2026.
- L4Good human trials
Added apitegromab with the Nature Medicine EMBRAZE Phase 2 trial: 1.9 kg less DXA-measured lean-mass loss than placebo at week 24 in 102 adults on tirzepatide (reported 54.9% relative retention).
Added at L4 for the specified lean-mass endpoint. DXA lean mass is not a functional outcome; strength, mobility and frailty benefits are not established. Reviewed 3 October 2026.
- L4Good human trials
Added Regeneron's 52-week controlled Phase 2 COURAGE results: DXA-measured lean mass changed by -7.3% with semaglutide alone, -5.8% with trevogrumab 25 mg plus semaglutide and -4.2% with 75 mg plus semaglutide. In the predefined MRI substudy, thigh fat-free muscle volume changed by -1.03, -0.29 and -0.32, respectively; the sponsor derived relative estimates of 71.8% and 68.9% less loss for the trevogrumab groups.
Added at L4 for specified body-composition measurements supported by a controlled Phase 2 trial. DXA lean mass is not synonymous with skeletal muscle; MRI thigh fat-free muscle volume is anatomically more specific but is not a functional outcome. The findings were sponsor-reported, presented at EASD 2026 and described as in press, not yet peer reviewed. They do not establish strength, power, mobility, falls, frailty, disability, muscle quality or long-term clinical benefit. The earlier triplet arm remains historical 26-week context, not a new 52-week result. Reviewed 2 October 2026.
- L4Good human trials
Added the narrow FDA-approved US adult-FOP indication for Pasatru (garetosmab-grts), including the FOP-specific Phase 3 OPTIMA lesion and clinician-assessed flare-up findings. Metabolic and body-composition use remains investigational.
L4 describes research maturity for the specified FOP outcomes; regulatory approval is displayed separately and does not automatically create L5 evidence or validate Activin A inhibition for obesity, weight loss, sarcopenia or lean-mass outcomes. The earlier COURAGE evidence is from a 26-week triplet arm and cannot establish an effect of garetosmab alone. EMA review remains separate, and no new 52-week triplet result was identified. Reviewed 2 October 2026.
- L5Repeated human trials
Added 2026 randomized human epigenetic-aging evidence, a smaller human pilot analysis, and late-life mouse lifespan evidence, with explicit separation between biomarker changes, mechanistic plausibility and unproven human longevity claims.
No overall compound-rating change. Semaglutide remains L5 because of its established approved clinical evidence base. The aging evidence is claim-specific: randomized human evidence currently supports changes in DNA-methylation aging biomarkers in a specific population, while lifespan extension has only been demonstrated in female mice. Human rejuvenation or lifespan extension is not established. Reviewed 1 October 2026.
- L3Early human studiesevidence rating changed
The Registry grading rubric now recognises preliminary blinded Phase 1 human observations as L3 research maturity, while treatment-attributable weight-loss efficacy remains unestablished.
Previously L2. Sponsor-reported results in eight participants (including two assigned placebo) remain blinded, so the reported mean weight change cannot be attributed to MBX 4291. Claim-specific efficacy is L1 and confidence very low. Reviewed 29 September 2026.
- L3Early human studies
Retained L3 for retrospective human exposure and symptom documentation, while musculoskeletal healing remains at L2 preclinical evidence.
The September 2026 preprint is uncontrolled and cannot establish causality. A registered Phase 2 trial has no posted efficacy results. Confidence remains very low. Reviewed 29 September 2026.
- L1Theory only
Retained L1 for research maturity and claim-specific evidence while the first-in-human study is under way.
The sponsor announced Phase 1 initiation; no qualifying compound-specific human outcome findings were established in the audited sources. Reviewed 29 September 2026.
- L1Theory only
The IGF-1 LR3 profile now states plainly that native IGF-1 is a legitimate 70-amino-acid polypeptide hormone, that pharmaceutical recombinant IGF-1 exists as mecasermin, and that LR3, R3 and DES(1-3) IGF-1 are documented analogues with published recombinant expression and measurable receptor activity — alongside a reusable four-question ladder separating those facts from what is inside an unregulated vial.
No rating change. The molecule literature is laboratory work and none of these analogues is an approved medicine. Identity and purity of a supplied product need analytical evidence on that material; folding, labelled quantity and biological activity are further separate questions, and a purity figure alone does not demonstrate a correctly folded, active protein. Reviewed 21 September 2026.
- Emerging & adjacent — four preclinical records added, two of them not peptidesL2Animal / lab studies
Added SLU-PP-915 (small-molecule oral pan-ERR agonist; 2026 mouse exercise-capacity paper and 2026 anti-doping LC-HRMS/MS characterisation), MA-5 / mitochonic acid 5 (small indole molecule binding mitofilin/Mic60, with the June 2026 Scientific Reports mouse mitochondrial-disease study), phoenixin-20 (SMIM20-derived neuropeptide; mitochondrial-biogenesis data are in cultured neuronal cells) and HDAP2 (cardiolipin-targeting peptide; 2026 mouse optic-nerve injury work).
All four are Level 2 preclinical with no established human efficacy or safety. Records now carry an explicit molecule type, so SLU-PP-915 and MA-5 are labelled small molecules rather than peptides. Animal and cell findings are not predictions of human benefit. Reviewed 20-21 September 2026.
- L2Animal / lab studies
Added a profile for VRX-0075, a single-molecule agonist reported at the GLP-1, GIP, glucagon, amylin and calcitonin receptors in ADA 2026 abstract 2839-LB, including a comparison against retatrutide in a rodent obesity model.
Added because online discussion, including the informal 'GLP-5' nickname, is far ahead of the evidence. The retatrutide comparison is rat-to-rat; there is no human efficacy or safety data. 'GLP-5' is community shorthand for five targets, not a receptor or drug class, and a disclosed research-support relationship is not evidence of suppression. Reviewed 20 September 2026.
- Experimental pipeline — early-stage amylin, incretin and GIP-antagonist candidates addedL1Theory only
Added VK3019 (Phase 1 dual amylin/calcitonin agonist, initiated 24 June 2026), MBX 4291 (Phase 1 GLP-1/GIP prodrug, preliminary sponsor-reported data), MBX 5765 and MBX 6180 (preclinical / IND-enabling), ASC36 and the ASC36_35FDC fixed-dose combination (US Phase 1 initiated 2026), EloraTZP (eloralintide + tirzepatide combination) and AT-7687 (GIP receptor antagonist, Phase 2a with semaglutide, first patient dosed 28 July 2026).
At the time of this September 20 catalogue entry, these records were graded L1–L2. MBX 4291 was subsequently revised to L3 research maturity on 29 September based on preliminary blinded human observations, without establishing efficacy. Combination products (ASC36_35FDC, EloraTZP) are filed as combinations rather than single molecules, and AT-7687 blocks the GIP receptor rather than activating it — the opposite direction to tirzepatide. Nisotirostide and macupatide were withheld pending primary sourcing for their current status. Reviewed 20 September 2026.
- L3Early human studiesevidence rating changed
A September 2026 preprint documented 1,039 BPC-157 users in retrospective clinical notes, while BPC-HAMSTR (NCT07437547), a planned 120-participant randomised, double-blind, placebo-controlled Phase 2 trial in acute Grade II hamstring strain, is recruiting with no results posted.
The rating moves from Level 2 to Level 3 only because the strongest study type is now uncontrolled human observational evidence. The reported 79% is 279 of 354 users with an ascertainable directional response, not all 1,039 users; 685 had no ascertainable response. The preprint cannot establish efficacy or causality, and trial registration is not positive efficacy evidence. Clinical certainty remains very low and no healing claim is proven. Reviewed 18 September 2026.
- Wolverine blend — BPC-157 exposure data does not test the marketed combinationL0Anecdote only
The Wolverine record now distinguishes BPC-157's informal 'Wolverine peptide' nickname from the seller-defined Wolverine or Wolverine stack label typically used for BPC-157 plus TB-500. The preprint documented TB-500 co-treatment in 12.9% of BPC-157 users but did not test a standardised combined product.
Wolverine remains Level 0. There is no controlled human efficacy or safety trial of the marketed BPC-157 + TB-500 combination, and evidence for either ingredient cannot be transferred to the combined vial. Reviewed 18 September 2026.
- L4Good human trials
Lilly reported that adults with obesity or overweight and type 2 diabetes lost up to a mean 49.6 lb (22.5 kg, 20.8%) and had HbA1c reductions of up to 1.6 percentage points at 80 weeks in TRIUMPH-2.
These are company-reported Phase 3 topline results announced on 15 September 2026, pending fuller scientific presentation and publication. Retatrutide remains investigational and unapproved, and another sponsor topline does not move its Level 4 rating. Reviewed 18 September 2026.
- L1Theory only
Added a new profile. Brenipatide (LY3537031) is a biologic dual agonist of the GIP and GLP-1 receptors listed on Eli Lilly's pipeline in Phase 3 development for alcohol use disorder and major depressive disorder. Two Phase 3 trials in alcohol use disorder are recruiting: RENEW-ALC-1 (NCT07219966, estimated N=1100, start 15 October 2025) and RENEW-ALC-2 (NCT07219953, estimated N=1100, start 16 October 2025), both randomised, double-blind and placebo-controlled with estimated primary completion in April 2028.
Added because active Phase 3 development, plus growing online claims that incretin drugs reduce craving or treat addiction, make this a compound readers will encounter. No efficacy results have been posted for any indication, so under our rubric the evidence level reflects mechanism and registered trials rather than demonstrated human outcomes. Registered late-stage trials are a question being tested properly, not an answer: brenipatide is not approved for alcohol use disorder, depression or anything else, and it is not a weight-loss medicine. Reviewed 11 September 2026.
- L5Repeated human trialsevidence rating changed
Our profile was stale. FDA approved Imcivree on 19 March 2026 for reduction of excess body weight and long-term weight maintenance in adults and paediatric patients aged 4 years and older with acquired hypothalamic obesity. The supporting global Phase 3 TRANSCEND trial (N=142) is cited in sponsor approval materials as showing an 18.4% placebo-adjusted BMI reduction at 52 weeks, and TRANSCEND results were subsequently published in the New England Journal of Medicine in July 2026.
The evidence level moved from Level 4 to Level 5 under our existing rubric, not because a new indication exists but because the underlying evidence base now meets the Level 5 test: a randomised placebo-controlled Phase 3 trial published in a peer-reviewed journal alongside earlier pivotal trials, plus a major regulator decision. The original genetic-obesity indications (including POMC, PCSK1 or LEPR deficiency and Bardet-Biedl syndrome) remain separate from the acquired hypothalamic obesity indication; neither makes setmelanotide a general weight-loss medicine, and none of this evidence transfers to common obesity without a defined genetic or hypothalamic cause. Reviewed 9 September 2026.
- L5Repeated human trials
Novo Nordisk announced STEP Young Phase 3 topline results on 7 September 2026 in children aged 6 to under 12 years with obesity. The trial met its primary endpoint: under the trial-product estimand, 40.4% of semaglutide-treated children were below the obesity BMI threshold after 68 weeks versus 0% on placebo, with both groups receiving lifestyle modification. Novo reported overall safety and tolerability consistent with previous adult and adolescent experience.
No rating moved. Semaglutide is already at the highest evidence level, and these are sponsor-reported topline results rather than peer-reviewed full data — the detailed efficacy and safety analyses in this age group have not yet been published or reviewed by a regulator for a paediatric weight-management indication in under-12s. The sponsor's tolerability statement is recorded as reported and not upgraded into a stronger safety conclusion. Reviewed 9 September 2026.
- GLP-1 medicines — US compounding law and the Fifth Circuit shortage rulingsL5Repeated human trials
Two regulatory threads updated. First, FDA's current position is explicit that retatrutide and cagrilintide cannot be used in compounding under US federal law, and FDA's refreshed warnings about unapproved and compounded GLP-1 products cite adverse-event reports, fraudulent or inaccurate labelling, semaglutide salt forms that are not the approved active ingredient, shipping without proper temperature control, and dosing errors with multi-dose vials. Second, the US Court of Appeals for the Fifth Circuit upheld FDA's shortage-list determinations: for tirzepatide on 27 August 2026, and for semaglutide in an opinion revised on 1 September 2026.
This is legal and regulatory evidence about US supply routes and product quality — not efficacy or safety evidence about the molecules. No evidence level, confidence score or safety score moved. The court decisions reinforce FDA's shortage delistings and the end of shortage-based routine copying of the approved products; they do not mean every form of individually tailored compounding is categorically unlawful, because narrow statutory exceptions can still apply. Retatrutide and cagrilintide remain investigational and unapproved everywhere; semaglutide and tirzepatide remain approved medicines whose approvals are product- and indication-specific. Reviewed 8 September 2026.
- Retatrutide and SS-31 / Elamipretide — FDA enforcement expands against grey-market sellersL5Repeated human trials
FDA issued warning letters dated 24 August 2026 to Royal Peptides LLC, Peptide Partners LLC and TXP Innovations LLC (dba Tex Peptides), identifying products marketed as retatrutide and as 'SS-31 (Elamipretide)' among unapproved new drugs. FDA states that injectable drug products sold this way are especially concerning because injection bypasses key body defences and can pose serious harm from unsafe, ineffective or poor-quality drugs.
This is regulatory and supply-chain evidence, not efficacy or toxicity evidence. No evidence level, confidence score or safety rating changed. Retatrutide remains investigational and unapproved everywhere; the letters simply confirm that US vendors selling products labelled as retatrutide are outside approved medical supply. For elamipretide, the approved Forzinity product for Barth syndrome in patients weighing at least 30 kg is unaffected — the letters concern unapproved vendor products labelled 'SS-31 (Elamipretide)', which are not that medicine. Nothing here indicates a new molecule-level toxicity signal for pharmaceutical-grade retatrutide or elamipretide. Reviewed 7 September 2026.
- L4Good human trials
Pivotal Phase 3 results now available: TRIUMPH-1 topline (21 May 2026) reported 28.3% average weight loss over 80 weeks in the 12 mg group, with 45.3% of participants losing at least 30% of body weight, and 30.3% average loss at 104 weeks in the higher-BMI extension.
Our human-efficacy score rose because the pivotal trial has now reported, but the evidence level and regulatory status did not move. These are sponsor topline announcements rather than peer-reviewed publications, and retatrutide is still not approved anywhere. Strong efficacy evidence and complete long-term safety evidence are different things.
- L4Good human trials
Lilly's 6 June 2026 update reported TRANSCEND-T2D-1 HbA1c reductions of up to 2.0 percentage points and weight loss of up to 16.8% at 40 weeks, plus further TRIUMPH findings in knee osteoarthritis and obstructive sleep apnoea.
Added as sponsor-reported trial results across additional populations. Breadth of reported benefit is not the same as regulatory acceptance, and none of these indications is approved.
- Orforglipron (Foundayo) — small-molecule GLP-1, not a peptideL5Repeated human trials
The MHRA authorised orforglipron in the UK on 10 August 2026 for weight management and maintenance in eligible adults, and for inadequately controlled type 2 diabetes.
Added to the GLP-1 Centre as a pipeline entry rather than a peptide profile, because orforglipron is an oral small molecule, not a peptide. For UK readers this is the most consequential recent change in the class: a GLP-1 receptor agonist in tablet form. Authorisation applies to defined uses only.
- L5Repeated human trials
Formulation and regulatory update: FDA approved a once-daily oral semaglutide 25 mg Wegovy tablet for chronic weight management on 22 December 2025, launched January 2026; the European Commission approved the Wegovy tablet and the 7.2 mg injection in July 2026.
The evidence level did not change; the product landscape did. There are now two distinct oral semaglutide products with different authorised uses — Rybelsus for type 2 diabetes and the oral Wegovy tablet for weight management. They are not interchangeable.
- L4Good human trials
Standalone cagrilintide has entered the RENEW Phase 3 programme. The REDEFINE-1 cagrilintide arm showed about 11.8% mean weight loss versus 2.3% with placebo at 68 weeks under the adherence estimand.
Amylin pharmacology now has a standalone late-stage test rather than existing mainly as a combination partner. CagriSema, the fixed-dose combination with semaglutide, is tracked separately as a GLP-1 Centre pipeline entry — combination results do not transfer to either component alone.
- BPC-157, KPV, TB-500, MOTS-c, DSIP/Emideltide, Epitalon, Semax, GHK-CuL1Theory only
Compounding-policy update: FDA's nominations document updated 22 April 2026 records several nominated peptide substances removed from the interim 503A Category 2 list because nominations were withdrawn, with advisory consultation planned. FDA then held a Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026 covering these substances.
This is a regulatory-process change, not a scientific one, and it is being widely misreported online. An advisory committee meeting is a policy consultation: it is not FDA approval, not a finding that any of these compounds works, and not a blanket legalisation. Our curated record does not establish a final FDA determination after that meeting, so the wording on each profile stays cautious.
- Registry-wideL2Animal / lab studies
Coverage expansion: registry grew from 55 to 69 curated profiles, adding current metabolic pipeline peptides (zenagamtide, eloralintide, petrelintide, survodutide, enicepatide, VK2735, pemvidutide) and heavily discussed research-market peptides (AOD-9604, ARA-290, PE-22-28, LL-37, PEG-MGF, IGF-1 LR3). A 'Currently discussed' watchlist and non-peptide pipeline cards were also added.
This is a coverage change, not a discovery. Community discussion decided what to cover; credible primary, official and peer-reviewed sources decided what could be said. Sponsor topline results are labelled as such rather than presented as peer-reviewed evidence, and names without gradeable sources went on the watchlist instead of getting invented profiles.
- Registry-wideL2Animal / lab studies
Editorial update: registry expanded from 42 to 56 curated compounds, adding major approved peptide medicines across oral, nasal, injectable and implant routes, plus a source-completeness layer on every profile.
This is a registry coverage change, not a new clinical discovery. Fourteen established medicines — from desmopressin and oxytocin to linaclotide and icatibant — were added so that approved peptide therapy across routes can be compared against research-market claims. Each profile now also shows whether its references are fully curated, partially curated or still pending, and outstanding placeholders (e.g. vasopressin, calcitonin) are marked openly rather than filled with weak links.
- Registry-wideL2Animal / lab studies
Editorial update: major taxonomy expansion from 15 to 42 curated compounds, adding approved peptide medicines and high-interest research compounds.
This is a registry coverage change, not a new clinical discovery. New categories (metabolic, gastrointestinal, bone-calcium, melanocortin, immune, antiviral, pain-neuro) and a new route (intrathecal) were added so that approved medicines — from bremelanotide to ziconotide — can be catalogued alongside the research compounds they are constantly confused with.
- L1Theory only
Editorial update: profiles created or revised using FDA 2026 Pharmacy Compounding Advisory Committee material.
This reflects curation of existing regulatory documents, not new clinical findings. FDA 2026 PCAC review material established, for example, that no clinical studies or human exposure data were identified for KPV via any route — a fact that sets the ceiling for every marketed claim about it.
- L2Animal / lab studies
Baseline entry: registry position set to preclinical-only for musculoskeletal healing claims.
Reviewed the available literature landscape. Preclinical breadth is large; controlled human evidence for tendon and injury claims remains absent, so confidence stays very low.
- L3Early human studiesevidence rating changed
Baseline entry: split rating into approved narrow indication versus general anti-ageing claims.
A rare-disease accelerated approval justifies a higher regulatory status but not higher confidence in longevity or performance claims. The registry now separates the two explicitly.
- L4Good human trialsevidence rating changed
Baseline entry: efficacy confidence for weight loss set high; safety confidence held low pending Phase 3 completion.
Randomised human trial data support large weight reduction. Long-term safety and a regulatory decision are still outstanding, so the two axes are rated separately.
- L2Animal / lab studies
Baseline entry: classified as promising-but-unproven rather than emerging therapy.
Human data are observational. Without a published trial of exogenous administration, therapeutic claims cannot rise above Level 2.
- L3Early human studiesevidence rating changed
Baseline entry: topical and systemic evidence separated into distinct positions.
Small topical cosmetic studies support modest skin-appearance effects. Injectable systemic use has no controlled human evidence and is rated independently.
- L2Animal / lab studies
Baseline entry: discontinued clinical development recorded in the profile.
Trials in postoperative ileus did not meet endpoints and development stopped. Physique claims have never been trialled.
- L4Good human trials
Baseline entry: added as combination-therapy candidate with moderate confidence.
Additive weight reduction in combination trials is supported. Standalone long-term evidence remains limited.
- L1Theory only
Baseline entry: lifespan-extension claims recorded as unsupported.
Supporting literature is historical, narrow and largely unreplicated. Mechanistic telomerase findings do not establish human outcomes.
Notable regulatory events
United States
FDA approved Pasatru (garetosmab-grts) to reduce formation of new heterotopic ossification lesions and clinician-assessed flare-ups in adults with FOP. This approval does not cover obesity or body-composition use; EMA review remains separate.
United States
FDA granted accelerated approval to Forzinity (elamipretide) for Barth syndrome in patients weighing at least 30 kg, on a surrogate endpoint with a confirmatory trial required. Does not cover anti-ageing or performance use.
United States
FDA approved Wegovy to reduce the risk of cardiovascular death, heart attack and stroke in adults with established cardiovascular disease and overweight or obesity.
United States
FDA granted accelerated approval to Wegovy for adults with noncirrhotic MASH with moderate-to-advanced liver fibrosis (F2-F3).
United States
FDA approved Zepbound as the first medication for obstructive sleep apnoea in adults with obesity.
China
NMPA approved mazdutide for chronic weight management. A regional approval; not approved in the US, UK or EU.
China
NMPA approved mazdutide for glycaemic control in adults with type 2 diabetes, its second Chinese indication.
United States
Approved for excess visceral abdominal fat in HIV-associated lipodystrophy only.
United States
FDA's Pharmacy Compounding Advisory Committee considered BPC-157-related substances for possible inclusion on the 503A Bulks List. Committee recommendations are non-binding: this compounding-policy process is not FDA drug approval, proof of efficacy or blanket legalisation. BPC-157 remains unapproved.
Global
Investigational only; advanced Phase 3 programme in obesity and metabolic disease.