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 ↗ Limited · human
This case report describes two adults living with well-controlled HIV-1 who presented with excess visceral abdominal fat (EVAF) under distinct clinical phenotypes. The first patient had a non-obese visceral adiposity phenotype (BMI 27 kg/m²) with increased waist circumference; treatment with tesamorelin, a growth hormone-releasing hormone analog, was associated with reductions in waist circumference, improved lipid levels, and enhanced functional well-being. The second patient had obesity (higher BMI) and received a GLP-1 receptor agonist; intermittent medication access led to fluctuating weight and persistent abdominal fat, after which the addition of tesamorelin was reported to provide more targeted visceral fat reduction. The authors argue that EVAF in people living with HIV can occur across BMI categories and may not be adequately captured by weight-based assessments alone. They conclude that individualized management informed by fat distribution patterns—rather than BMI or weight—is warranted. Key limitations include the single case-report design (n=2), absence of a control condition, lack of imaging-based visceral fat quantification reporting, and inability to draw generalizable conclusions about comparative efficacy.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 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 ↗ Animal only
This study examined how combination antiretroviral therapy (cART) interacts with calorie-dense diets to affect heart function in a rat model. One hundred and twenty weanling Sprague Dawley rats were assigned to one of three diets (normal chow, calorie-dense low-protein, or calorie-dense normal-protein) for 15 weeks, then subdivided into four treatment groups for an additional 9 weeks: saline control, dolutegravir (DTG) plus tesamorelin, DTG alone, or a classical cART regimen. At week 24, electrocardiographic (ECG) recordings and myocardial tissue analysis were performed. The study found statistically significant differences across groups in multiple ECG parameters, including Q, R, S, and T wave amplitudes, PR interval, QRS duration, ST height, and corrected QT interval. Myocardial fibrosis was notably observed in animals receiving DTG alone or classical cART while on calorie-dense diets. The authors suggest these structural changes may disrupt electrical conduction and predispose to arrhythmias. Notably, tesamorelin appeared to attenuate these cardiac effects, leading the authors to implicate growth hormone pathway dysfunction in the pathology. Key limitations include the exclusive use of an animal model, meaning findings may not directly translate to humans.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 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 ↗ Strong · human
This meta-analysis pooled data from five randomized controlled trials (RCTs) to evaluate the effects of tesamorelin — a synthetic growth hormone-releasing hormone (GHRH) analogue — compared with placebo in adults living with HIV who have lipodystrophy. The authors conducted a systematic search of five major databases through July 2025 and applied a random-effects meta-analysis model, assessing risk of bias with RoB 2.0 and certainty of evidence using GRADE. The analysis found that tesamorelin was associated with a statistically significant reduction in visceral adipose tissue (mean difference of approximately −27.71 cm²), as well as improvements in hepatic fat content, lean body mass, and IGF-1 levels. The study authors reported that these benefits occurred without clinically significant adverse effects on glucose metabolism or serious safety signals. Limitations of the analysis include the small number of included trials (n=5), potential variability across trial populations and durations, and the inherent constraints of meta-analytic methodology in establishing causality. The findings suggest tesamorelin may offer metabolic and body composition benefits in HIV-associated lipodystrophy, though the authors note the results should be interpreted within the context of the underlying evidence base.
Obesity research & clinical practice · Jan 2026DOI ↗ Review
This narrative review examines the problem of lean body mass (LBM) loss associated with weight loss, with particular focus on incretin-based therapies such as GLP-1 receptor agonists (e.g., semaglutide) and dual GIP/GLP-1 receptor agonists (e.g., tirzepatide). The authors queried PubMed, Medline, and Scopus for randomized controlled trials and Phase II/III trials related to obesity, muscle loss, and lean mass preservation, excluding animal studies. The review outlines the physiological mechanisms driving muscle loss during caloric deficit—including reduced anabolic signaling, increased protein catabolism, and hormonal changes—and surveys pharmacological agents under investigation to counteract these effects. Key drug classes discussed include bimagrumab (an activin receptor antagonist targeting the myostatin pathway), tesamorelin (a growth hormone-releasing hormone agonist), and enobosarm (a selective androgen receptor modulator). The authors note that while incretin-based therapies represent a major advance in obesity management, the accompanying loss of muscle mass is a clinically meaningful concern. Most agents targeting LBM preservation are in early research phases. Limitations include reliance on narrative rather than systematic methodology, potential selection bias in study inclusion, and the rapidly evolving evidence base in this area.
Journal of clinical medicine · Jan 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 6-month phase 2 randomized open-label clinical trial investigated whether tesamorelin, a growth hormone-releasing hormone analog, could improve neurocognitive impairment (NCI) in people with HIV who were virally suppressed on antiretroviral therapy and had abdominal obesity (elevated waist circumference). Seventy-three participants were randomized 3:2 to tesamorelin or standard of care (SOC). The primary outcome was change in neurocognitive performance at 6 months; secondary outcomes included waist circumference, mood, and daily functioning. The tesamorelin group showed a non-significant trend toward improved neurocognitive performance (mean change 0.146; P=.060), while the SOC group did not improve (P=.295); crucially, the between-group difference was not statistically significant (P=.673). Tesamorelin did produce a significantly greater reduction in waist circumference versus SOC (median difference −2.7 cm; P=.015). IGF-1 levels rose in the tesamorelin group but did not correlate with cognitive or waist circumference changes. Key limitations include an open-label (non-placebo-controlled) design, modest sample size resulting in insufficient statistical power, and the relatively short 6-month follow-up. The authors concluded there was no clear cognitive benefit from short-term abdominal obesity reduction with tesamorelin in this population.
The Journal of infectious diseases · Jun 2025DOI ↗ Review
This review examines metabolic dysfunction-associated steatotic liver disease (MASLD) as it specifically affects people with HIV (PWH). The authors highlight that MASLD is highly prevalent in this population and follows a more aggressive clinical course than in HIV-negative individuals. The review discusses how HIV-specific factors — including altered body composition, chronic immune activation, enhanced gut permeability, and antiretroviral therapy (ART) side effects — compound the common pathogenic mechanisms of MASLD, accelerating disease progression. The authors note the recent adoption of updated MASLD nomenclature and the first FDA-approved MASLD therapy, emphasizing that these advances have not yet been adequately studied in PWH. They identify a critical evidence gap in evaluating emerging MASLD therapies specifically within this population. Among interventions studied in PWH, the review highlights early promise from glucagon-like peptide-1 (GLP-1) receptor agonists and the growth hormone-releasing hormone analog tesamorelin. The authors conclude that MASLD is a meaningful driver of both liver-related and cardiovascular morbidity in PWH, and that the distinct pathophysiology of MASLD-HIV necessitates tailored diagnostic and management strategies. Limitations include the review format and the scarcity of dedicated clinical trial data in PWH.
Current opinion in HIV and AIDS · May 2025DOI ↗ Limited · human
This retrospective pharmacovigilance study examined whether specific drugs are disproportionately associated with carpal tunnel syndrome (CTS) reports in the FDA Adverse Event Reporting System (FAERS) database between October 2003 and September 2024. Using OpenVigil 2.1, researchers applied disproportionality analysis—primarily reporting odds ratios (RORs)—supplemented by Bayesian confidence propagation neural network algorithms to identify significant drug-CTS signals. Out of nearly 13 million adverse event reports, 6,837 (0.05%) involved CTS, with female patients comprising 69.5% of cases and a mean age of 57 years. Ten drugs showed strong, statistically significant associations with CTS reports: enzyme replacement therapies (idursulfase, galsulfase, laronidase), the growth hormone-releasing factor analog tesamorelin, the aromatase inhibitor anastrozole, bisphosphonates (alendronic acid, alendronate), gamma-hydroxybutyric acid (GHB), the COX-2 inhibitor rofecoxib, and the transthyretin stabilizer tafamidis. The study's key limitations include its reliance on spontaneous reports (subject to underreporting, reporting bias, and confounding), an inability to establish causality, and lack of exposure-denominator data. The authors conclude that clinicians should be alert to CTS symptoms in patients prescribed these medications.
Limited · human
This sub-analysis leveraged a randomized, double-blind, placebo-controlled trial of 61 people with HIV (PWH) and metabolic dysfunction-associated steatotic liver disease to assess whether tesamorelin remains effective and safe among those specifically on integrase inhibitor (INSTI)-based antiretroviral regimens. Of 38 participants on INSTIs at baseline, 15 (tesamorelin) and 16 (placebo) completed 12 months of follow-up. The study used MRI, proton MR spectroscopy, and DEXA to quantify visceral fat area, hepatic fat fraction, and trunk-to-appendicular fat ratio. The tesamorelin group showed statistically significant reductions in all three body composition endpoints compared to placebo. Metabolic safety outcomes, including rates of hyperglycemia, were similar between arms, and the drug was generally well tolerated. The authors note this is the first dataset specifically addressing tesamorelin use in PWH on INSTI-based regimens—an important gap given that phase III approval trials predated widespread INSTI use. Key limitations include the small sub-group sample size, the sub-analysis design (not powered for this specific comparison), and the predominantly research-selected population, which may limit generalizability.
AIDS (London, England) · Jun 2024DOI ↗ 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 ↗ 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 ↗