// 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'
D
BPC-157 is safe for chronic use in humans
No controlled long-term human safety data.
Module 06 · BPC-157, TB-500 & 'Healing Peptides'
F
BPC-157 is FDA-approved for any indication
It is not.
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