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 ↗ Animal only
This preclinical study examined whether two ghrelin mimetics (growth hormone secretagogue receptor 1a agonists), anamorelin and ipamorelin, could reduce cisplatin-induced weight loss, appetite suppression, and vomiting in ferrets — an established animal model of chemotherapy-induced nausea and emesis. In isolated ferret ileum tissue, both compounds inhibited electrically-stimulated gut contractions, with anamorelin showing a greater maximum inhibitory effect. When administered intraperitoneally before and after cisplatin, neither compound reduced acute or delayed vomiting episodes, but both reduced associated weight loss by approximately 24% during the late delayed phase (48–72 hours). Strikingly, when anamorelin was delivered directly into the brain (intracerebroventricularly), it reduced acute emesis by approximately 60%, improved food and water intake during the acute phase by roughly 20–40%, and reduced delayed-phase weight loss by approximately 23%. These findings suggest that anamorelin's anti-emetic effects depend on central nervous system penetration rather than peripheral action. Limitations include the use of a single non-human animal species, small group sizes typical of ferret studies, and the invasive intracerebroventricular route, which is not clinically practical. No human data were generated.
Physiology & behavior · Jul 2024DOI ↗ Animal only
This study investigated the effects of ipamorelin acetate (IPA), a synthetic ghrelin agonist, on the reproductive axis of male Mozambique tilapia (Oreochromis mossambicus), a cichlid fish. Fish received either 5 µg or 30 µg of IPA over 21 days and were compared to untreated controls. The study found that IPA administration produced a dose-dependent increase in food intake. Histological analysis revealed significant increases in primary spermatocytes, secondary spermatocytes, and early spermatids in both treatment groups, while the higher dose also increased late spermatids, lobule area, and lumen area. Serum concentrations of luteinizing hormone (LH) and the fish androgen 11-ketotestosterone (11-KT) were significantly elevated in both IPA groups. Androgen receptor protein expression was significantly upregulated in the high-dose group. No significant differences in hypothalamic or pituitary GnRH-immunoreactive fiber density were observed across groups. The authors conclude that ghrelin signaling may promote meiosis-I stage germ cell development through LH stimulation at the pituitary level and 11-KT and androgen receptor activity at the testicular level. Limitations include the use of a single non-mammalian species, a short treatment duration, and the absence of mechanistic pathway confirmation.
Animal reproduction science · Jul 2024DOI ↗ Animal only
This animal study investigated whether ghrelin receptor agonists (ghrelin mimetics) could reduce visceral and somatic pain in the absence of active inflammation. Using a rat model, researchers induced non-inflammatory visceral hypersensitivity by infusing dilute acetic acid into the colon, and somatic mechanical allodynia was also assessed. Two ghrelin receptor agonists were tested: HM01, a centrally and peripherally active compound administered orally, and ipamorelin, a peripherally restricted compound administered intravenously. Pain responses were measured by counting abdominal muscle contractions during colorectal distension (visceral pain) and paw withdrawals to von Frey filament stimulation (somatic pain). The study found that both HM01 and ipamorelin significantly reduced colonic hypersensitivity and somatic allodynia compared to vehicle controls. These effects were reversed by co-administration of the ghrelin receptor antagonist H0900, confirming that the anti-nociceptive effects were receptor-mediated. Notably, the peripherally restricted compound ipamorelin was effective, suggesting peripheral ghrelin receptor activation may be sufficient. The study is limited by its exclusive use of an animal model, meaning translational relevance to humans remains unestablished. The authors propose ghrelin mimetics as a potential novel approach for treating acute visceral and somatic pain.
Journal of experimental pharmacology · Aug 2020DOI ↗ Review
This narrative review examines the potential adjunctive role of growth hormone secretagogues (GHS) in managing body composition changes associated with male hypogonadism and metabolic syndrome. The authors acknowledge that while testosterone replacement therapy remains the standard of care for hypogonadism, its body composition benefits are inconsistent across patient populations. The review surveys existing literature on five GHS compounds — sermorelin, GHRP-2, GHRP-6, ibutamoren (MK-677), and ipamorelin — noting that all stimulate growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion and may improve body composition metrics such as reducing fat mass and attenuating muscle atrophy. The authors also explore their potential utility in eugonadal males with metabolic syndrome or subclinical hypogonadism. A major limitation explicitly acknowledged by the authors is the scarcity of robust clinical trial data evaluating these compounds specifically in hypogonadal men. The review concludes that while GHS show theoretical and preliminary promise as complementary agents, the current evidence base is insufficient to draw firm clinical conclusions, and the authors call for future controlled investigations. No new primary data are presented.
Translational andrology and urology · Mar 2020DOI ↗ Limited · human
This study developed and validated an analytical method for detecting a broad panel of 18 performance-enhancing peptides (molecular weight <2 kDa) in human urine, as defined by the World Anti-Doping Agency (WADA) prohibited list. The method uses direct urine injection—bypassing complex sample preparation—coupled with liquid chromatography and ion mobility time-of-flight mass spectrometry (IM-TOFMS). The researchers reported limits of detection (LOD) ranging from 50 to 500 pg/mL, well below WADA's minimum required performance level of 2 ng/mL. The method demonstrated acceptable precision (imprecision <20%) and linearity across a 0–10 ng/mL working range. Stability testing identified –20°C as the appropriate storage temperature for urine samples. As a proof-of-concept, the method was applied to real elimination study urine samples from individuals who had administered GHRP-2, GHRP-6, or LHRH, successfully detecting these compounds. Key limitations include the small number of human subjects used in the elimination studies, which were primarily intended to demonstrate analytical feasibility rather than investigate pharmacokinetics or clinical effects. The study is a methodological/analytical validation paper focused on anti-doping screening, not a clinical or therapeutic investigation.
Journal of separation science · Dec 2015DOI ↗ Animal only
This study compared the pharmacokinetics of five peptidyl growth hormone secretagogues — ipamorelin (NNC 26-0161), NNC 26-0194, NNC 26-0235, GHRP-2, and GHRP-6 — in male rats using multiple routes of administration, with a particular focus on nasal delivery. Following intravenous bolus injection, all peptides showed biexponential plasma concentration decline. Ipamorelin stood out with a systemic plasma clearance approximately five times lower than GHRP-6. Excretion routes differed: ipamorelin was primarily cleared via urine, while GHRP-6 and the two NNC peptides were predominantly excreted in bile. Metabolic stability was moderate for ipamorelin and the NNC peptides, with 60–80% of administered doses recoverable as intact peptide from bile and urine combined. Intranasal bioavailability of ipamorelin was estimated at approximately 20%, while NNC 26-0235, NNC 26-0194, and GHRP-2 achieved approximately 50% nasal bioavailability. The authors concluded that nasal delivery appears to be a promising route for this peptide class. Key limitations include exclusive use of animal subjects (male rats), meaning findings may not directly translate to humans, and the study did not assess pharmacodynamic or safety endpoints.
Xenobiotica; the fate of foreign compounds in biological systems · Nov 1998DOI ↗