Review
This structured narrative review synthesized contemporary evidence (January 2020–August 2025) on injectable peptides used in orthopaedics and sports medicine, drawing from PubMed/MEDLINE, Embase, and Web of Science. The authors identified five functional peptide classes: GLP-1 receptor agonists (e.g., semaglutide), collagen-derived injectables, regenerative peptides (e.g., BPC-157, thymosin derivatives), growth hormone secretagogues (e.g., CJC-1295, ipamorelin, tesamorelin), and related compounds. The review found that GLP-1 receptor agonists were the only class supported by reproducible randomized evidence for musculoskeletal benefit—specifically symptomatic improvement in knee osteoarthritis—attributing this primarily to weight loss and putative anti-inflammatory effects rather than proven structural cartilage modification. Collagen-derived preparations showed only preliminary signals from small, single-center prospective studies. All remaining classes were deemed investigational, carrying unresolved safety profiles, significant product quality concerns, and widespread antidoping restrictions. Risk of bias was appraised for included human trials. The authors concluded that clinical use of injectable peptides should be restricted to approved agents for established indications or rigorously designed research protocols, and that clinicians should counsel athletes about uncertain efficacy, safety risks, and antidoping consequences. The study was assigned Level V evidence and a predominantly Grade C strength of recommendation.
JBJS reviews · May 2026DOI ↗ InsufficientPreprint
This study analyzed a large, publicly available independent testing dataset of 6,441 samples spanning fourteen peptide compounds sold through largely unregulated gray market channels directly to consumers. Compounds examined included BPC-157, semaglutide, tirzepatide, PT-141, TB-500, thymosin beta-4, and others marketed for purposes such as injury recovery, muscle growth, fat loss, and athletic performance. Researchers applied two quality acceptance frameworks — one approximating standards for 503A compounded medications and a stricter model reflecting FDA-approved drug production standards — to assess purity, measured abundance, and endotoxin burden. The study found that between 41.6% and 71.1% of samples failed to meet basic quality criteria depending on the framework applied, and measurable endotoxin contamination was detected in 15% of samples. Gray market peptides were consistently cheaper than FDA-approved alternatives, though cost differentials varied widely (e.g., 72.8% higher for tirzepatide vs. 3,850% higher for PT-141 when comparing FDA-approved options). The authors concluded that consumer-directed third-party testing improves transparency but captures only a fraction of the full safety profile relevant to patients self-administering injectable compounds. Key limitations include reliance on a secondary dataset not collected under controlled research conditions and the inability to assess many other safety dimensions beyond purity and endotoxin levels.
Unknown journal · Apr 2026DOI ↗ Review
This narrative review examines the pharmacological mechanisms, safety profiles, and regulatory status of twelve peptides commonly marketed in sports medicine contexts, spanning both FDA-approved compounds (e.g., tesamorelin/Egrifta) and unapproved "gray market" substances (e.g., BPC-157, CJC-1295, TB-500, ipamorelin, and others). The authors note that while many unapproved peptides show promising tissue repair and metabolic effects in animal models, rigorous human safety and efficacy data are largely absent. The review highlights a growing direct-to-consumer gray market operating outside regulatory oversight and discusses the potential for serious patient harm. Notably, the authors address the placebo effect as a possible mediator of perceived peptide efficacy and examine how social media may amplify this effect. A clinician-oriented framework is proposed to guide evidence-based patient discussions about peptide use for musculoskeletal healing and athletic performance, including consideration of alternative treatments. Key limitations include the narrative (non-systematic) review methodology and the inherently limited and heterogeneous evidence base for most compounds discussed, particularly in human populations.
Sports medicine (Auckland, N.Z.) · Apr 2026DOI ↗ ReviewPreprint
This narrative review examines the pharmacological mechanisms, safety profiles, and regulatory status of twelve peptides commonly encountered in sports medicine and athletic performance contexts, including both approved agents (e.g., tesamorelin/Egrifta, sermorelin) and unapproved "gray market" compounds (e.g., BPC-157, CJC-1295, TB-500, ipamorelin, AOD-9604, FS-344, GHK-Cu, MOTS-C, SS-31, and thymosin beta-4). The authors note that while many unapproved peptides show promising tissue repair and metabolic outcomes in animal models, rigorous human safety and efficacy data remain scarce. The review highlights the emergence of a direct-to-consumer gray market operating outside regulatory oversight and the potential for serious patient harm. It further discusses the placebo effect as a potential mediator of perceived peptide efficacy, and how social media may amplify this effect. The authors provide a clinical framework to guide patient-provider discussions and promote evidence-based practice for musculoskeletal healing. Key limitations include the narrative (non-systematic) review design, reliance on preclinical literature for most unapproved compounds, and the absence of head-to-head human trials for the majority of agents discussed.
Unknown journal · Apr 2026DOI ↗ Review
This comprehensive narrative review examines nine therapeutic peptides with proposed applications in healthy aging and age-related conditions: tirzepatide (metabolic dysfunction), epitalon (telomere biology), GHK-Cu (dermal regeneration), BPC-157 and TB-500 (tissue repair), Semax (neuroprotection), CJC-1295 and ipamorelin (growth hormone modulation), and bremelanotide (sexual function). The authors searched PubMed, Scopus, and regulatory databases through January 2026, selecting 20 primary sources based on relevance and methodological quality. The review found that FDA-approved agents such as tirzepatide and bremelanotide have robust safety and efficacy data from large-scale trials, while investigational peptides such as epitalon, BPC-157, and TB-500 show promising signals primarily from preclinical and limited clinical studies. The authors highlight significant knowledge gaps, including the absence of long-term safety data for non-approved peptides, undefined optimal dosing regimens, unknown combination therapy effects, and lack of validated biomarkers for monitoring efficacy. The authors conclude that while therapeutic peptides offer mechanistically diverse approaches to aging hallmarks, investigational agents require rigorous clinical trial validation before clinical adoption. As a narrative review, findings are subject to selection bias and do not represent a quantitative synthesis of evidence.
Frontiers in aging · Apr 2026DOI ↗ Review
This critical review examines the emerging use of peptides and peptide analogues as performance-enhancing drugs in both competitive sport and recreational bodybuilding. The authors survey a range of compounds — including growth hormone secretagogues (e.g., Ipamorelin), growth hormone-releasing hormone analogues (e.g., CJC-1295, Sermorelin), and synthetic peptide fragments (e.g., Frag 176-191, KPV) — which are promoted in bodybuilding communities for purported benefits in muscle growth, fat loss, recovery, and anti-inflammation. The review notes that these compounds are attractive partly due to their enhanced receptor selectivity and stability compared to older anabolic agents. However, the authors conclude that clinical evidence supporting their use in sport contexts is limited; most existing research addresses therapeutic applications under controlled medical settings, not the high-dose or stacked protocols typical in bodybuilding. The review identifies potential risks including cardiovascular strain, insulin resistance, dyslipidemia, and psychiatric instability. It also highlights the dangers posed by an unregulated supply chain prone to mislabeling and contamination. Anti-doping detection remains challenging due to peptides' structural similarity to endogenous hormones and short half-lives. A key gap identified is the near-complete absence of population-level prevalence data, particularly for recreational users. The authors characterize peptide use in sport as high-risk and ethically problematic pending longitudinal safety evidence.
The Journal of sports medicine and physical fitness · Mar 2026DOI ↗ Review
This narrative review examines the potential role of therapeutic peptides in orthopaedic care, synthesizing preclinical and mechanistic literature across several peptide classes. The authors categorize peptides by their primary proposed function: wound-healing agents (BPC-157, TB-500, GHK-Cu), growth hormone secretagogues (ipamorelin, CJC-1295, tesamorelin, sermorelin, AOD-9604), recovery-enhancing peptides (epithalon, delta sleep-inducing peptide, pinealon), and neuroactive peptides (selank, semax, dihexa). The review describes how these compounds are theorized to interact with signaling pathways—including PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK—to promote tissue regeneration, resolve inflammation, and support neuromuscular recovery. The authors acknowledge that, while preclinical evidence is promising, robust human clinical trial data are largely absent, representing a significant gap in the literature. Limitations include the review's reliance on animal and in vitro studies, the absence of a systematic search methodology, and the lack of direct clinical evidence supporting efficacy or safety in human orthopaedic populations. The authors call for future controlled trials to validate these mechanistic findings in clinical settings.
Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · Jan 2026DOI ↗ Review
This narrative review, aimed at orthopaedic and sports medicine physicians, synthesizes the existing biochemical and clinical literature on six commonly marketed injectable therapeutic peptides: BPC-157, TB-4, TB-500, CJC-1295 + ipamorelin, tesamorelin, and GHK-Cu. The authors conducted a PubMed literature search and evaluated evidence across preclinical and clinical settings. Key findings attributed to the reviewed studies include: BPC-157 showed potential in tendon and muscle repair in preclinical models, with one human case series reporting pain reduction after intra-articular knee injection, though that study had significant methodological limitations and no control group. TB-4 and TB-500 demonstrated angiogenesis and tissue repair effects in animal models, but no human orthopaedic data were identified, and both are banned in sport. CJC-1295 combined with ipamorelin improved muscle tension in a murine glucocorticoid-induced muscle loss model only. Tesamorelin holds FDA approval for HIV-associated lipodystrophy but lacks orthopaedic evidence. GHK-Cu showed wound healing and anti-inflammatory properties preclinically, with no clinical musculoskeletal data. The authors conclude that indications, safety profiles, and dosing for all these peptides remain undefined for orthopaedic use, and robust human trials are needed before clinical recommendations can be made.
The American journal of sports medicine · Jan 2026DOI ↗ ReviewPreprint
This review paper examines the pharmacological mechanisms, safety profiles, and regulatory status of both approved and unapproved peptide therapies relevant to sports medicine, musculoskeletal injury recovery, and athletic performance enhancement. The compounds reviewed span a wide spectrum — from FDA-approved agents such as tesamorelin and sermorelin, to gray-market compounds including BPC-157, TB-500, CJC-1295, Ipamorelin, AOD-9604, FS-344, GHK-Cu, MOTS-C, and SS-31. The authors note that while many unapproved peptides show promising results in preclinical and animal models — including favorable tissue repair and metabolic effects — rigorous human safety and efficacy data remain scarce. The review highlights a growing direct-to-consumer gray market operating outside regulatory oversight and discusses how social media may amplify perceived benefits through placebo-related mechanisms. The paper also offers a clinical framework to guide patient conversations and support evidence-based decision-making. Key limitations include the inherent constraints of a narrative review design, reliance on heterogeneous preclinical data for unapproved compounds, and the absence of controlled human trials for most of the highlighted peptides.
Unknown journal · Dec 2025DOI ↗ Insufficient
This study focused on the development and validation of an analytical detection method — not a clinical intervention — for identifying growth hormone-releasing hormone (GHRH) and its synthetic analogs (sermorelin/CJC-1293, tesamorelin, and CJC-1295) in human urine samples for anti-doping purposes. These peptides are banned by the World Anti-Doping Agency (WADA) due to their potential performance-enhancing effects. The researchers developed a nano liquid chromatography coupled with quadrupole/orbitrap mass spectrometry (nano-LC-Q/Orbitrap MS) approach, systematically optimizing sample preparation steps including solid-phase extraction (SPE) and ultrafiltration. The finalized workflow — ultrafiltration followed by SPE — was fully validated per WADA guidelines, assessing selectivity, reliability, limits of detection (LOD ≤ 0.5 ng/mL), limits of identification (LOI 0.5–0.75 ng/mL), carryover, robustness, autosampler stability, and matrix effects. The method demonstrated sufficient sensitivity for both screening and confirmation of target peptides in urine. A key limitation is that this is a purely analytical/methodological study; it provides no clinical, pharmacological, or physiological data about the effects of these peptides in humans, and its findings are confined to laboratory detection performance.
Journal of pharmaceutical and biomedical analysis · Oct 2025DOI ↗ Limited · human
This study developed and validated a unified chromatographic-mass spectrometric (LC-MS) method for detecting a broad range of prohibited peptide drugs (molecular mass 2–10 kDa) in doping control urine samples. The target analytes spanned five categories: insulins (human and animal-derived, including several analogues and a metabolite), growth hormone-releasing hormones (GHRHs) and their metabolites, insulin-like growth factors (IGF variants), synacthen, gonadorelin, and mechano growth factors. A key goal was simplifying sample preparation by consolidating what are traditionally separate, complex analytical workflows into a single procedure, controlled by five internal standards—one per peptide category. The method was validated as an initial testing procedure and shown to meet nearly all World Anti-Doping Agency (WADA) Minimum Required Performance Levels (MRPLs). As a proof of principle, the method was applied to authentic post-administration urine samples from human subjects dosed with insulins and gonadorelin, demonstrating real-world detection capability. Limitations include that human subject data are limited to proof-of-concept post-administration samples rather than a controlled efficacy or pharmacological trial, and the study's primary focus is analytical method development rather than clinical outcomes.
Journal of mass spectrometry : JMS · Jan 2024DOI ↗ Insufficient
This study, conducted by a doping control laboratory, describes the development and analytical validation of a method for detecting growth hormone-releasing hormones (GHRHs) — specifically tesamorelin, CJC-1295, sermorelin (GRF 1-29), sermorelin (3-29)-NH₂, and somatorelin — in human urine samples. GHRHs are prohibited in sport under World Anti-Doping Agency (WADA) regulations. The method combines weak cation exchange solid-phase extraction (SPE) with ultra-high-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). The researchers validated the method according to WADA technical documents, evaluating selectivity, limit of detection (LOD), carryover, reliability, stability, and recovery. The method achieved an LOD of 0.2 ng/mL, a limit of quantification (LOQ) of 0.6 ng/mL, and linearity from 0.1 to 1.2 ng/mL. The study reports adequate recovery and sensitivity for routine anti-doping screening. A key limitation is that this is purely an analytical/method-development study; it does not investigate pharmacological effects, clinical outcomes, or administer any compound to human or animal subjects.
Analytical biochemistry · Oct 2023DOI ↗ Limited · human
This study investigated a method for detecting a broad range of peptide-based doping agents (molecular mass 2–10 kDa) in blood samples collected for anti-doping control purposes. Researchers developed a simplified, generic sample preparation workflow using mixed-mode solid-phase extraction (SPE), coupled with liquid chromatography and high-resolution mass spectrometry (HRMS; resolution >100,000 FWHM) as an initial testing procedure. The target analytes included multiple insulin variants (human and synthetic analogues such as lispro, aspart, glulisine, detemir, glargine, and others), growth hormone–releasing hormones (sermorelin, CJC-1295, tesamorelin), insulin-like growth factors (Long-R3-IGF-I, R3-IGF-I, Des1-3-IGF-I), and mechano growth factors. The study demonstrated that the method met WADA's Technical Document 2022 (TD2022 MRPL) requirements for minimum required performance levels. Proof-of-principle was shown using real post-administration blood samples from subjects treated with synthetic insulin analogues. A key advantage noted was that blood, unlike urine, contains intact peptide hormones at relatively higher concentrations, simplifying detection. Limitations include the study's primarily analytical/methodological scope and the small number of post-administration samples used for validation.
Analytical science advances · Aug 2022DOI ↗ Insufficient
This study developed and validated an antibody-free analytical method for detecting prohibited growth hormone-releasing hormone (GHRH) analogues — specifically sermorelin, CJC-1293, a sermorelin metabolite, CJC-1295, and tesamorelin — in human urine samples. Instead of the conventional, labor-intensive immunoaffinity purification approach, the researchers used ultrafiltration alone to preconcentrate urine samples before analysis by nano liquid chromatography coupled with high-resolution tandem mass spectrometry (nanoLC-HRMS/MS). The method achieved limits of detection between 5 and 25 pg/mL and limits of identification between 25 and 50 pg/mL, with analyte recoveries of 59–115%. Robustness was demonstrated across over 200 injections. When compared directly to immunoaffinity purification, the ultrafiltration approach yielded similar sensitivity at lower cost and without requiring specialized antibodies. Stability experiments revealed that sermorelin and its metabolite degrade rapidly at temperatures above 4°C and at pH below 7, highlighting the critical importance of proper sample handling. The authors note the method could be extended to other emerging peptide drugs (≥ ~3 kDa) and their metabolites. A key limitation is that the study is an analytical methods validation paper rather than a clinical or pharmacological study; it does not assess biological effects or pharmacokinetics in human subjects.
Journal of pharmaceutical and biomedical analysis · Mar 2022DOI ↗ In vitro
This study, motivated by anti-doping enforcement, investigated the in vitro metabolism and urinary detection of four synthetic growth hormone releasing hormone (GHRH) analogs: sermorelin, tesamorelin, CJC-1295, and CJC-1295 with drug affinity complex (DAC). Because these compounds are banned by the World Anti-Doping Agency (WADA) yet rarely detected in accredited laboratory samples—likely due to low urinary concentrations and poorly understood metabolism—researchers used in vitro methods to identify 19 major metabolites. These metabolites were synthesized, purified, and characterized in-house to serve as reference materials. Using these standards alongside commercially available parent compounds and one known sermorelin metabolite (sermorelin(3-29)-NH₂), the team developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method applied to fortified (spiked) urine samples. Limits of detection were generally at or below 1 ng/mL, meeting WADA's required performance threshold. Key limitations include the in vitro nature of the metabolism work, meaning real-world in vivo metabolite profiles in humans may differ, and no actual athlete or clinical urine specimens were analyzed. The study advances analytical capability for anti-doping testing but does not evaluate physiological or clinical effects of these peptides.
Drug testing and analysis · Nov 2021DOI ↗ Review
This review paper surveys the current landscape of analytical methods used in sports anti-doping laboratories to detect peptide-based drugs, drug candidates, and their analogs in biological specimens such as blood, serum, and urine. The authors describe the broad range of peptidic compounds subject to anti-doping scrutiny, spanning low-molecular-mass peptides (e.g., growth hormone-releasing peptides, ARA-290, TB-500, AOD-9604, CJC-1295, desmopressin) to intermediate-mass proteins (e.g., insulins, IGF-1, growth hormone, erythropoietin) and higher-molecular-mass biologics (e.g., stamulumab). The review outlines detection approaches including chromatographic-mass spectrometric, electrophoretic, immunological, and combined methodologies, emphasizing the challenge of proving exogenous origin at very low concentrations in limited sample volumes. A central finding is that a meaningful gap remains between what is technically achievable in detection and what is routinely practiced in day-to-day analytical workflows. Limitations of this paper include its nature as a narrative review rather than an original experimental study, meaning it synthesizes existing literature without generating new empirical data. It does not evaluate clinical outcomes or therapeutic efficacy of any compound discussed.
Expert review of proteomics · Nov 2014DOI ↗