// Evidence Grader
Claim grades, A through F
Every major peptide claim in this course gets a transparent grade. Use this dashboard to audit what's established, what's preliminary, and what's hype.
A
Clinically established
B
Supported, context-specific
C
Promising, preliminary
D
Plausible, unproven
E
Popular, weak support
F
Misleading or false
A
Semaglutide reduces major adverse cardiovascular events in patients with established CVD and obesity
SELECT trial 2023, NEJM. Pivotal. ~20% MACE reduction.
Module 01 · Why Peptides Matter Now
A
Tirzepatide produces ≥15% mean weight loss in obesity at 72 weeks
SURMOUNT-1 (NEJM 2022). Established at 15 mg dose.
Module 01 · Why Peptides Matter Now
D
BPC-157 promotes tendon and ligament healing in humans
Strong rat data; essentially no controlled human trials. Compounded only.
Module 01 · Why Peptides Matter Now
F
Compounded GLP-1s from 503A pharmacies are equivalent to brand-name semaglutide
FDA has issued multiple warnings; salt forms (semaglutide sodium/acetate) are not the same molecule and have caused dosing errors and adverse events.
Module 01 · Why Peptides Matter Now
C
GHK-Cu reverses skin aging when applied topically
Some controlled cosmetic studies; effect size modest. Systemic 'anti-aging' claims are unsupported.
Module 01 · Why Peptides Matter Now
F
Epitalon extends human lifespan
Marketing claim with no rigorous human evidence.
Module 01 · Why Peptides Matter Now
A
Lipidation extends peptide half-life via albumin binding
Established for liraglutide, semaglutide, insulin detemir/degludec.
Module 02 · Peptide Pharmacology Fundamentals
A
Oral semaglutide (Rybelsus) achieves clinically useful exposure via SNAC permeation enhancer
PIONEER program; ~1% bioavailability is enough at 7–14 mg doses.
Module 02 · Peptide Pharmacology Fundamentals
D
Anti-drug antibodies routinely cause loss of efficacy with GLP-1 RAs
Clinically uncommon at population level; matters more for exenatide than semaglutide.
Module 02 · Peptide Pharmacology Fundamentals
A
Semaglutide reduces 3-point MACE by ~20% in patients with established CVD without diabetes (SELECT)
Lincoff et al., NEJM 2023.
Module 03 · GLP-1 Receptor Agonists
A
Semaglutide reduces composite kidney/CV outcome in T2D + CKD (FLOW)
Perkovic et al., NEJM 2024. Trial stopped early for benefit.
Module 03 · GLP-1 Receptor Agonists
C
GLP-1 RAs slow Parkinson's disease progression
Lixisenatide LIXIPARK (NEJM 2024) modest signal; exenatide PD-2 negative. Pre-specified meta still hypothesis-generating.
Module 03 · GLP-1 Receptor Agonists
D
Semaglutide causes thyroid C-cell tumors in humans
Rodent finding; human signal uncertain. Class label remains, MTC/MEN2 remain contraindications.
Module 03 · GLP-1 Receptor Agonists
F
Compounded GLP-1s save patients money safely during shortages
FDA adverse-event reports include dosing errors, overdoses, and infections; salt forms are not interchangeable.
Module 03 · GLP-1 Receptor Agonists
A
Tirzepatide outperforms semaglutide on weight loss head-to-head (SURMOUNT-5)
Tirzepatide −20.2% vs semaglutide −13.7% at 72 wk.
Module 04 · Tirzepatide & Multi-Agonists
C
Triple agonists (retatrutide) will have a comparable safety profile to GLP-1 RAs at scale
Glucagon-arm hepatic and energy-expenditure effects need long-term observation.
Module 04 · Tirzepatide & Multi-Agonists
A
Tesamorelin reduces visceral adipose tissue in HIV-associated lipodystrophy
FDA-approved 2010 based on RCT data.
Module 05 · Growth Hormone Secretagogues
D
CJC-1295 + ipamorelin safely improves body composition in healthy adults
No published RCTs; compounded only; raises IGF-1 with mitogenic concerns.
Module 05 · Growth Hormone Secretagogues
E
MK-677 (ibutamoren) is safe for chronic use in healthy adults
Studies in elderly showed ↑ glucose, ↑ HbA1c, edema, CHF signal in frail.
Module 05 · Growth Hormone Secretagogues
B
BPC-157 accelerates tendon healing in rats
Replicated rodent data; not human.
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
B
BPC-157 protects rat GI mucosa against NSAID- and alcohol-induced injury
Multiple preclinical models; mechanism plausibly via NO/COX modulation.
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
C
BPC-157 stimulates angiogenesis via VEGFR-2 up-regulation
Endothelial cell + rat hindlimb-ischemia data (Hsieh 2017); independent replication limited.
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
C
BPC-157 has antidepressant-like effects in rodents (Porsolt test) and counters serotonin-syndrome features via 5-HT2A modulation
Sikiric/Boban-Blagaic group; not replicated independently in humans.
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
B
BPC-157 is well tolerated in rat (up to 20 mg/kg single IM; 4 mg/kg/day × 28 d) and beagle preclinical toxicology
Xu et al. 2020 GLP toxicology — preclinical only.
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
D
BPC-157 has a defined human pharmacokinetic profile
Only one scant human PK report (Veljaca 2002); the registered Phase I trial NCT02637284 was withdrawn.
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
D
BPC-157 is safe for chronic use in humans
No controlled long-term human safety data; theoretical pro-angiogenic risk.
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
F
BPC-157 is legal to compound under FDA 503A
Placed on 503A Category 2 list (significant safety risk) in 2023.
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
F
BPC-157 is FDA-approved for any indication
It is not — anywhere.
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
D
BPC-157 is explicitly named on the WADA Prohibited List
Not named, but on the WADA Monitoring Program; in competition falls under S0 (non-approved substances).
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
D
TB-500 promotes cardiac repair in humans
Preclinical only; abandoned in clinical development.
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
C
Topical GHK-Cu modestly improves photoaged skin appearance
Small controlled cosmetic studies.
Module 07 · GHK-Cu, Copper Peptides & Skin/Hair
F
Injected GHK-Cu reverses systemic aging
Marketing claim; no evidence.
Module 07 · GHK-Cu, Copper Peptides & Skin/Hair
B
MOTS-c improves insulin sensitivity in mice
Replicated preclinical.
Module 08 · MOTS-c & Mitochondrial Peptides
D
MOTS-c safely augments human exercise capacity
No controlled human trials.
Module 08 · MOTS-c & Mitochondrial Peptides
A
Setmelanotide produces meaningful weight loss in POMC, PCSK1, LEPR deficiency
Phase 3 pivotal trials.
Module 09 · Melanocortins: PT-141 & Melanotan
B
Melanotan-II is associated with new atypical naevi and melanoma case reports
Multiple case reports/series; no RCT.
Module 09 · Melanocortins: PT-141 & Melanotan
A
Oxytocin is effective for labor induction/augmentation
Standard of care.
Module 10 · Oxytocin, Vasopressin & Social/Endocrine Peptides
F
Intranasal oxytocin treats autism
Multiple negative phase II/III trials.
Module 10 · Oxytocin, Vasopressin & Social/Endocrine Peptides
A
GnRH agonists are first-line for advanced prostate cancer ADT
Decades of guideline support.
Module 11 · GnRH Analogs, Somatostatin & Oncology Peptides
A
PRRT extends PFS in midgut NETs
NETTER-1, NEJM 2017.
Module 11 · GnRH Analogs, Somatostatin & Oncology Peptides
C
Topical Matrixyl reduces wrinkle depth
Small controlled cosmetic studies.
Module 12 · Aesthetic & Cosmetic Peptides
C
Cerebrolysin improves recovery after acute ischemic stroke
Meta-analyses suggest modest signal; heterogeneous trials.
Module 13 · Cognitive & Nootropic Peptides
F
Dihexa is a safe nootropic for healthy adults
No human safety data.
Module 13 · Cognitive & Nootropic Peptides
A
FDA placed BPC-157 in category 2 in 2023
Documented FDA bulks list update.
Module 14 · Safety, Regulation & Compounded Peptides
B
Compounded peptides bypass FDA quality oversight
503A compounding is not subject to NDA review; only USP 797/800 + state board oversight.
Module 14 · Safety, Regulation & Compounded Peptides
B
Retatrutide phase II showed >24% mean weight loss at 48 wk
Jastreboff NEJM 2023; phase III pending.
Module 15 · Controversies, Pipeline & Frontier
C
Bimagrumab preserves lean mass during weight loss
Phase II signal; activin pathway.
Module 15 · Controversies, Pipeline & Frontier
F
Epitalon extends human lifespan
No rigorous human RCTs. Mouse data and small open-label observational reports from a single research group only.
Module 16 · Khavinson 'Bioregulator' Peptides — Deep Dive
E
Epitalon improves sleep architecture (objective polysomnography)
No published controlled PSG data in healthy adults. Self-report studies are uncontrolled.
Module 16 · Khavinson 'Bioregulator' Peptides — Deep Dive
D
Epitalon upregulates telomerase activity in human cells
Small in-vitro studies (Khavinson 2003); not independently replicated at scale.
Module 16 · Khavinson 'Bioregulator' Peptides — Deep Dive
F
Pinealon is neuroprotective in humans
Almost entirely cell-culture and rodent data from one group.
Module 16 · Khavinson 'Bioregulator' Peptides — Deep Dive
F
Vesugen normalizes vascular function
Same institutional source; no Western RCTs.
Module 16 · Khavinson 'Bioregulator' Peptides — Deep Dive
D
Cortexin improves cognitive recovery after stroke
Used in Russian neurology; trials are mostly Russian-language, small, and not blinded by Western standards.
Module 16 · Khavinson 'Bioregulator' Peptides — Deep Dive
F
Khavinson peptides are FDA-approved for any indication
None are. Several are on the FDA's 2023 Category 2 list, barring 503A compounding.
Module 16 · Khavinson 'Bioregulator' Peptides — Deep Dive
F
Compounded Epitalon/Pinealon from a US 503A pharmacy is a legal therapeutic option
FDA Category 2 (2023) explicitly bars 503A compounding of these substances.
Module 16 · Khavinson 'Bioregulator' Peptides — Deep Dive
E
The 'Russian Cosmonaut Program' validated bioregulators in humans
Frequently cited in marketing; no peer-reviewed RCT corresponds to this claim.
Module 16 · Khavinson 'Bioregulator' Peptides — Deep Dive
A
Most FDA-approved peptide therapeutics are analogs of an endogenous human peptide
Insulin, glucagon, GLP-1 RAs, somatostatin analogs, vasopressin analogs, PTH(1-34), GnRH agonists/antagonists, calcitonin, oxytocin — all derive from human peptide signaling.
Module 17 · Endogenous Human Peptides & Exotic Animal Peptides
A
Exenatide was developed from a peptide in Gila monster (Heloderma suspectum) saliva
Exendin-4, isolated by John Eng at the Bronx VA in 1992; FDA-approved as exenatide in 2005.
Module 17 · Endogenous Human Peptides & Exotic Animal Peptides
A
Ziconotide is a synthetic version of a Conus magus cone snail venom peptide
ω-conotoxin MVIIA; FDA-approved 2004 for severe chronic pain via intrathecal infusion; N-type calcium channel blocker.
Module 17 · Endogenous Human Peptides & Exotic Animal Peptides
A
Captopril's design was inspired by a bradykinin-potentiating peptide from Bothrops jararaca pit viper venom
BPP-9a led Sergio Ferreira and the Squibb team to the first oral ACE inhibitor (1981) — peptide-to-small-molecule translation.
Module 17 · Endogenous Human Peptides & Exotic Animal Peptides
A
Eptifibatide is derived from a barbourin peptide in Sistrurus barbouri (southeastern pygmy rattlesnake) venom
KGD-motif disintegrin; cyclic heptapeptide GPIIb/IIIa antagonist; FDA-approved 1998.
Module 17 · Endogenous Human Peptides & Exotic Animal Peptides
A
Calcitonin-salmon is more potent at the human calcitonin receptor than human calcitonin
Higher receptor affinity and longer half-life — classic example of a non-human ortholog outperforming the human peptide.
Module 17 · Endogenous Human Peptides & Exotic Animal Peptides
F
Tardigrade Dsup protein is an approved or near-approved human therapeutic
Dsup (damage-suppressor) is in early in-vitro/preclinical investigation only. No clinical trials.
Module 17 · Endogenous Human Peptides & Exotic Animal Peptides
F
Naked mole-rat HMW-hyaluronan or related peptides are clinically available cancer therapies
Mechanistically intriguing; zero approved derivatives.
Module 17 · Endogenous Human Peptides & Exotic Animal Peptides
D
Bear hibernation 'peptides' can be used in humans to preserve muscle during bed rest
Active research area (HP-20c complex, urea-nitrogen recycling); no human therapeutics.
Module 17 · Endogenous Human Peptides & Exotic Animal Peptides
C
Antarctic icefish antifreeze glycopeptides are used in clinical organ preservation
Investigational for hypothermic preservation fluids; not standard of care.
Module 17 · Endogenous Human Peptides & Exotic Animal Peptides