Limited · human
This study investigated the detection of ibutamoren (MK-677), a growth hormone secretagogue, in human hair samples to aid forensic interpretation of anti-doping hair test results. Two scenarios were examined: (1) a single 10 mg oral dose administered to a male volunteer, with hair collected 4 weeks later; and (2) hair collected from an individual who had consumed 60 capsules of 10 mg ibutamoren over 90 days, also sampled 4 weeks after discontinuation. Researchers developed a liquid/liquid extraction method using bicalutamide-D4 as an internal standard, with a validated linear range of 0.5–250 pg/mg and a limit of detection of 0.1 pg/mg. The study found that a single 10 mg dose produced a positive hair result at 1.3 pg/mg in the 0–1 cm segment, while the prolonged-use scenario yielded 224 pg/mg in the 0–4 cm segment. The authors conclude that these findings establish, for the first time, ibutamoren's incorporation into human hair and provide reference concentration ranges to support interpretation of hair test results in anti-doping proceedings. Key limitations include the very small sample size (essentially two subjects) and the non-controlled nature of the second case.
Clinica chimica acta; international journal of clinical chemistry · Aug 2025DOI ↗ Limited · human
This Phase 1 randomized, double-blind, placebo-controlled trial examined the safety and efficacy of mazdutide — a dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist — at doses up to 16 mg in adults with overweight or obesity but without diabetes. Thirty-two participants received once-weekly subcutaneous injections of mazdutide (n=24, split across two dose-escalation cohorts) or placebo (n=8) for 20 weeks. The study found that both mazdutide cohorts experienced substantially greater mean percent reductions in body weight from baseline (approximately -20% and -21%, respectively) compared to the placebo group (approximately -0.1%), with statistically significant differences. The authors also reported improvements in metabolic markers and concluded that the 16 mg dose was well tolerated. Key limitations include the small sample size (particularly the placebo group of only 8 participants), the short 20-week duration, the Phase 1 design which is primarily safety-focused, and the absence of participants with diabetes, limiting generalizability. These findings suggest a dose-response relationship at higher doses than previously studied, but larger and longer trials are needed to confirm these results.
Diabetes, obesity & metabolism · Aug 2025DOI ↗ Limited · human
This systematic review examined the existing literature on BPC-157 (Body Protection Compound-157), a naturally occurring gastric pentadecapeptide, specifically through the lens of orthopedic sports medicine. Researchers searched PubMed, Cochrane, and Embase for English-language studies published from database inception through June 2024. Of 544 identified articles, 36 met inclusion criteria — 35 preclinical studies and only 1 clinical study. Preclinical findings suggested BPC-157 may enhance growth hormone receptor expression, promote angiogenesis, stimulate cell growth pathways, and reduce inflammatory cytokines, with improved functional, structural, and biomechanical outcomes reported across muscle, tendon, ligament, and bone injury models. The sole clinical study was a retrospective case series in which 7 of 12 patients reported musculoskeletal pain relief lasting more than 6 months following intraarticular injection for chronic knee pain. The compound was found to be hepatically metabolized with a half-life under 30 minutes and renally cleared. Preclinical safety data showed no adverse effects across multiple organ systems; no clinical safety data were identified. The authors note that BPC-157 lacks FDA approval and is banned in professional sports, and caution about risks from unregulated manufacturing. The review is limited almost entirely to preclinical evidence, leaving significant gaps in human safety and efficacy data.
HSS journal : the musculoskeletal journal of Hospital for Special Surgery · Jul 2025DOI ↗ Limited · human
This paper presents a case report of a man in his early 30s who developed transaminitis (elevated liver enzymes) after taking MK-677, an oral growth hormone secretagogue, for approximately two months. MK-677 has been growing in popularity as a performance-enhancing supplement. The patient was otherwise healthy, with no other apparent causes for liver injury identified. Following discontinuation of the supplement, liver function tests gradually returned to normal levels, suggesting a causal relationship between MK-677 use and the hepatotoxic event. The authors highlight that while known side effects of MK-677 include oedema, increased appetite, and muscle pain, reports of hepatotoxicity associated with its use are rare. This case adds to the limited literature on potential adverse hepatic effects of MK-677. Key limitations include the single-patient design, lack of a liver biopsy or formal causality assessment score (e.g., RUCAM), inability to fully exclude confounders such as contaminants in the supplement, and the inherent difficulty in establishing definitive causality from a single case report.
BMJ case reports · Jul 2025DOI ↗ Limited · human
This pilot study investigated whether targeting estrogen-related receptors (ERRs) could help counteract muscle atrophy associated with physical inactivity in older women. Twenty women undergoing hip replacement surgery were divided into active (n=10) and inactive (n=10) groups based on self-reported activity levels. Muscle biopsies were collected during surgery and analyzed for key proteins involved in mitochondrial function and oxidative stress. Active women showed greater muscle fiber diameter, better handgrip strength, and lower pain scores. Inactive women's muscle tissue showed higher NOX4 (an oxidative stress marker) and lower levels of SIRT1, PGC-1α, ERRα, and FNDC5 compared to active women. In a separate cell-culture experiment, myoblasts isolated from inactive women's muscle tissue were treated with the ERR agonist SLU-PP-332. Treatment was associated with reduced NOX4, increased SIRT1, PGC-1α, ERRα, FNDC5, Akt, and Bcl-2 expression, decreased cytotoxicity, oxidative stress, and cellular senescence, increased glutathione levels, and enhanced myotube formation. The authors suggest ERR activation as a potential therapeutic strategy for muscle atrophy, while acknowledging that the small sample size, self-reported activity classification, and in vitro nature of the intervention data limit conclusions.
Frontiers in physiology · Jul 2025DOI ↗ Limited · human
This observational study investigated the relationship between serum Thymosin β4 (Tβ4) levels and Kawasaki disease (KD) in children, with a specific focus on coronary artery lesions (CALs). Researchers measured serum Tβ4 concentrations via ELISA in children diagnosed with KD and age-matched healthy controls, further subdividing the KD group into those with and without CALs. The study found that serum Tβ4 levels were significantly lower in children with KD compared to healthy controls, and were reduced even further in KD patients who developed CALs. Following intravenous immunoglobulin (IVIG) treatment, Tβ4 levels increased significantly. Correlation analyses revealed negative associations between Tβ4 and several cytokines, including pro-inflammatory markers (TNF-α, IL-1β) and anti-inflammatory markers (IL-4, IL-10). The authors suggest that Tβ4 may play a role in KD's inflammatory pathogenesis and the progression of coronary artery involvement, proposing it as a potential diagnostic or therapeutic target. Key limitations include the observational design, which precludes causal inference, the pediatric-specific and single-condition focus, and the reliance on serum biomarker associations without mechanistic validation in this population.
Journal of inflammation research · Jul 2025DOI ↗ Limited · human
This retrospective observational study used the TriNetX database of de-identified electronic health records (January 2018–December 2020) to compare cardiovascular outcomes between semaglutide and dulaglutide in adults with type 2 diabetes. From a pool of nearly 4.7 million patients with type 2 diabetes, 231,075 semaglutide initiators and 189,103 dulaglutide initiators were identified. Propensity score matching yielded 171,105 patients per group. Over a 3-year follow-up, the study found that semaglutide was associated with statistically significantly lower rates of all-cause death (4.2% vs. 5.6%; HR 0.75, 95% CI 0.72–0.78), acute myocardial infarction (5.2% vs. 5.6%; HR 0.94), stroke (5.8% vs. 6.4%; HR 0.90), and acute heart failure hospitalization (5.3% vs. 6.1%; HR 0.88) compared with dulaglutide. Key limitations include the observational, non-randomized design, which is susceptible to residual confounding despite propensity score matching; reliance on administrative/EHR coding for outcome ascertainment; and the inability to distinguish between semaglutide formulations (oral vs. injectable) or account for dosing differences between agents.
Scientific reports · Jul 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 ↗ Limited · humanPreprint
This observational study examined the relationship between salivary oxidized forms of thymosin β4 (Tβ4) and thymosin β10 (Tβ10) and oxidative stress-related diseases in preterm infants born before 30 weeks of gestation. Researchers collected 149 saliva samples from 18 infants and analyzed the intact salivary proteome using nano-HPLC-ESI-MS, with relative quantification based on extracted ion current (XIC) peak area. The study found that post-menstrual age correlated significantly with total Tβ4, oxidized Tβ4 percentage, and total Tβ10. Higher fraction of inspired oxygen (FiO₂) values were associated with lower levels and percentages of oxidized Tβ10. Thymosin levels did not differ between infants with or without retinopathy of prematurity; however, higher oxidized Tβ10 levels were observed in infants who did not develop bronchopulmonary dysplasia (BPD), leading the authors to suggest a possible protective role for oxidized Tβ10 in inflammation and tissue repair. Key limitations include the very small sample size (18 infants), observational design, and the inability to establish causality. The authors propose saliva as a non-invasive matrix for future monitoring of oxidative stress in neonates.
Unknown journal · May 2025DOI ↗ Limited · human
This cross-sectional study examined self-reported outcomes among 486 adults in Kuwait who were using or had previously used GLP-1 receptor agonist (GLP-1 RA) injections — Semaglutide (n=181), Liraglutide (n=152), or Tirzepatide (n=132) — for weight loss, surveyed between February and May 2024. Participants completed an online questionnaire covering demographics, weight change, side effects, and quality of life. The study found that Tirzepatide users reported the highest average monthly and annual weight loss, along with the greatest satisfaction (88%) and most frequently reported improvements in quality of life (60%) compared to the other two agents. Side-effect profiles differed across groups: Tirzepatide users more commonly reported belching, while Liraglutide users reported higher rates of anxiety and were more likely to switch medications. No statistically significant differences were observed between groups in BMI, dietary adherence, or treatment compliance. Key limitations include the cross-sectional, self-report design, recruitment via online survey (introducing selection bias), lack of clinical verification of outcomes, and the inability to establish causality. The study also does not account for differences in duration of use, dosing, or baseline characteristics across groups.
Frontiers in nutrition · 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 prospective qualitative study surveyed 104 consecutive patients attending a pigmented lesion clinic at a tertiary referral dermatology centre in Ireland to examine the characteristics, attitudes, and behaviours of sunbed users. Using an anonymous self-reported questionnaire, researchers collected data on demographics, frequency of sunbed use, motivations, and use of unregulated tan-enhancing agents such as Melanotan I and II. The study found that sunbed users were predominantly younger women living in urban areas, consistent with prior literature. Regulatory non-compliance was widespread: over half of sunbed premises reportedly did not provide protective goggles, and nearly half offered no health risk information to customers. Key motivations for use included improving appearance and self-confidence. Notably, greater awareness of health risks did not correlate with reduced sunbed use, suggesting a potentially compulsive or addictive behavioural pattern. Users of tan-enhancing agents also used sunbeds more frequently than non-users. The authors suggest psychological interventions such as cognitive behavioural therapy may be beneficial and call for stricter regulatory enforcement. Limitations include the single-centre design, small sample size, self-reported data susceptible to bias, and a clinic-based population that may not represent the general public.
Skin health and disease · May 2025DOI ↗ Limited · human
This study investigated the role of CCN5, a matricellular protein, in preventing vascular restenosis after stent implantation (in-stent restenosis, ISR). Using RNA sequencing of stent-implanted porcine coronary arteries and single-cell RNA sequencing of mouse femoral artery injury models, the researchers found that CCN5 expression was reduced in vascular smooth muscle cells (VSMCs) following injury but elevated in regenerating endothelial cells (ECs). In ISR patients, plasma CCN5 levels were significantly lower and correlated inversely with restenosis severity. Using cell-type-specific loss- and gain-of-function mouse models, the study found that EC- and VSMC-specific deletion of CCN5 worsened neointimal hyperplasia, while CCN5 overexpression was protective. Mechanistically, CCN5 was found to interact with thymosin β4 (Tβ4) in ECs, promoting endothelial repair via the cleavage product Ac-SDKP, and also interacted with CD9 to support EC recovery. A CCN5 recombinant protein (CCN5rp)-coated stent deployed in a porcine model significantly increased endothelial strut coverage and reduced neointimal formation. Limitations include the translational gap between animal models and humans, and the observational nature of the patient plasma data.
European heart journal · May 2025DOI ↗ Limited · human
This retrospective, non-interventional drug utilization cohort study examined real-world prescribing patterns of two liraglutide formulations in the United Kingdom: Saxenda® (3.0 mg, approved for weight management) and Victoza® (1.2/1.8 mg, approved for type 2 diabetes). Using anonymized primary care data from the Clinical Practice Research Datalink (CPRD Aurum and GOLD databases), researchers identified 604 Saxenda® initiators and 4,853 Victoza® initiators who had no prior liraglutide prescription in the preceding 12 months. Descriptive statistics characterized demographics and drug utilization patterns. The study found that, where body weight data were available, 96.4% of Saxenda® initiators met the weight loss indication criteria. Saxenda® users were predominantly female (86.4%), younger (mean age ~46.5 years), and had shorter follow-up periods compared to Victoza® users. The authors concluded that both formulations were mostly prescribed in line with their approved indications and that real-world use raised no new safety signals. Key limitations include incomplete weight data for approximately half of Saxenda® initiators, the observational nature of the study, and reliance on administrative/primary care records, which may not capture all clinical details or secondary care prescribing.
Diabetes, obesity & metabolism · Apr 2025DOI ↗ Limited · human
This paper reports the case of a 22-year-old female who developed a mucosal malignant melanoma of the anterior maxilla following use of Melanotan II, an unlicensed synthetic analogue of melanocyte-stimulating hormone (α-MSH) administered as a nasal spray for cosmetic tanning purposes. Histological analysis confirmed the malignant melanoma diagnosis, and the patient was subsequently treated with surgical resection followed by immunotherapy. The authors conducted a supporting literature review examining the potential association between Melanotan II use and malignant melanoma development. They note that Melanotan II is illegal to sell in the United Kingdom and many other countries due to its unlicensed status and safety concerns. The paper highlights awareness of serious potential adverse effects linked to Melanotan II use. As a single case report, it cannot establish causation between Melanotan II use and oral mucosal melanoma; the temporal association is notable but confounding factors and the rarity of the event limit broader conclusions. The authors call for greater public and clinical awareness of risks associated with unregulated tanning peptides.
International journal of oral and maxillofacial surgery · Apr 2025DOI ↗ Limited · human
This German post-authorisation safety study (PASS; EUPAS13004) evaluated the real-world safety and clinical effectiveness of afamelanotide 16 mg (SCENESSE) in 200 patients with erythropoietic protoporphyria (EPP), a rare inherited disorder causing severe acute phototoxicity upon light exposure. As an ongoing observational study linked to the European EPP Disease Registry, it collected treatment-emergent adverse events as the primary safety variable and used the validated EPP-Quality of Life (EPP-QoL) tool alongside treatment continuity as effectiveness measures. The study found that afamelanotide's real-world safety and benefit-risk profile was consistent with that observed in prior clinical trials. Patients reported a statistically significant improvement in quality of life compared to baseline (p-value not fully quoted in the abstract). High treatment continuity was also noted, suggesting ongoing clinical benefit. Key limitations include the absence of an untreated comparator group within this cohort, the observational (non-randomised) design, and potential for selection bias inherent in registry-based studies. The authors concluded that afamelanotide demonstrated a positive safety profile and was associated with improved quality of life in EPP patients under real-world conditions.
Photodermatology, photoimmunology & photomedicine · Mar 2025DOI ↗ Limited · human
This small open-label proof-of-concept study investigated whether thymosin alpha-1 (Tα1), a thymic peptide hormone, might reduce depressive symptoms in five patients with common variable immunodeficiency (CVID) who also had a comorbid depressive episode. The rationale was that CVID patients share immune abnormalities with major depressive disorder (MDD) patients — notably reduced naïve T cells and premature T-cell senescence — and that Tα1 can stimulate thymic output of naïve T cells, potentially improving mood via immune-limbic system pathways. Patients received Tα1 subcutaneously over eight weeks and were assessed using the Hamilton Depression Rating Scale (HDRS) alongside immune biomarkers. All five CVID patients showed reductions in HDRS scores (average 52%), compared to a 36% average reduction in a non-randomized contrast group of 42 MDD patients receiving treatment as usual. Naïve/memory T-cell ratios improved in all five patients, and IL-6 levels decreased in four of the five. However, depressive and immune improvements were not sustained in a subsequent eight-week wash-out period for the more severely affected patients. Key limitations include the very small sample size (n=5), lack of a placebo control, open-label design, and use of a non-matched contrast group. The authors conclude that larger placebo-controlled trials are warranted.
Brain, behavior, & immunity - health · Jan 2025DOI ↗ Limited · human
This market surveillance study investigated the quality and safety risks of semaglutide products sold without a prescription through illegal online pharmacies. Researchers analyzed 1,080 links from search engine results pages, identifying 59 unique illegal online pharmacy websites. Web traffic data showed the top 30 affiliated domains accumulated over 4.7 million visits in a three-month period. Test purchases were attempted from six illegal vendors; three injection vials were delivered (three prefilled pens were never delivered, representing e-commerce scams). Visual inspection of the vials revealed noncompliance in 59–63% of evaluated packaging criteria, flagging them as probable substandard or falsified products. Laboratory analysis using liquid chromatography–mass spectrometry found semaglutide content exceeded labeled amounts by 28.56–38.69%, while measured purity was critically low (7.7–14.37%), far below the 99% claimed on labels. Endotoxin contamination was detected in all samples (2.16–8.95 EU/mg), posing a serious injection safety risk. No viable microorganisms were detected at the time of testing. The study's limitations include a small number of purchased samples and a single geographic/time window of surveillance. The authors conclude that unregulated online semaglutide markets present significant public health risks analogous to earlier waves of illicit erectile dysfunction drug sales.
Journal of medical Internet research · Nov 2024DOI ↗ Limited · human
This case report describes a 40-year-old male who developed bilateral gynecomastia and biochemical hypogonadotropic hypogonadism after approximately six months of using commercially available performance-enhancing supplements. Laboratory analysis of the three supplements identified several banned performance-enhancing drugs (PEDs): RAD-140 (a selective androgen receptor modulator), MK-677 (a growth hormone secretagogue), and cardarine. In vitro testing also revealed undisclosed hormones — testosterone, estradiol, and growth hormone — present in all three products. Liquid chromatography-mass spectrometry further identified an uncharacterized compound eluting near the testosterone peak. Upon cessation of all supplements, the patient experienced full clinical and biochemical resolution of his symptoms, including normalization of gonadotropin and testosterone levels. The authors argue this case underscores the importance of clinicians considering commercially available supplements as potential covert sources of exogenous PEDs and steroid hormones. Key limitations include the single-patient design, which precludes generalization, the inability to isolate which specific compound(s) caused the adverse effects, and the lack of confirmed identity of the uncharacterized coeluting compound.
JCEM case reports · Aug 2024DOI ↗ 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 ↗