Insufficient
This entry reviews the available information on bremelanotide, a cyclic peptide (molecular weight ~1025 Da), specifically in the context of breastfeeding safety. The review notes a complete absence of published clinical data on bremelanotide use during lactation. The authors reason that, based on its physicochemical properties as a large cyclic peptide, transfer into breast milk is theoretically expected to be minimal. Furthermore, even if trace amounts were present in milk, oral absorption by a nursing infant would likely be negligible, as the peptide would probably be degraded by proteolytic enzymes in the infant's gastrointestinal tract. Despite this theoretical reassurance, the review concludes that caution is warranted during breastfeeding due to the lack of empirical data, with particular emphasis on vulnerability in newborn and preterm infants, whose gastrointestinal and hepatic systems are less mature. The primary limitation of this entry is that it is entirely inference-based, drawing on pharmacokinetic principles rather than any direct human or animal lactation studies. No measured milk concentration data, infant outcome data, or controlled observations are cited.
Unknown journal · Feb 2025Source ↗ 🧪 TrialInsufficient
Registered Phase 4 interventional trial (active not recruiting). This study is being done to assess the efficacy of a saliva- based biomarker to predict response to semaglutide for the treatment of obesity.
ClinicalTrials.gov · Feb 2025View trial ↗ Preclinical
This study developed a composite hydrogel wound dressing (termed "GEK") by combining two food-derived biomaterials — oxidized konjac glucomannan (OKGM) from konjac and egg white (EW) proteins — cross-linked via Schiff base bonds to create a self-healing scaffold. The natural tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu (GHK-Cu) was incorporated into this hydrogel matrix. Researchers characterized the material's mechanical, self-repairing, and adhesive properties, then evaluated its biological performance in vitro and in vivo (likely using rodent infected wound models). The study reports that the GEK hydrogel demonstrated antibacterial and anti-inflammatory activity, promoted hemostasis through tissue adhesion, and supported neovascularization and skin regeneration. The all-natural composition was highlighted for its biocompatibility and biodegradability, with the authors proposing it as a cost-effective clinical strategy for infected wound management. Key limitations include that this is a preclinical materials science study with no human clinical data; evidence of efficacy is derived from laboratory and animal experiments. The translation of these findings to human wound care remains to be established through clinical trials.
Biomaterials research · Feb 2025DOI ↗ Animal only
This mouse study investigated whether intranasal administration of ghrelin, GHRP-6, or MK-0677 could activate the brain's ghrelin signaling system. Researchers first screened compounds and doses by measuring food intake after intranasal application. Of the three compounds tested, only GHRP-6 at a specific dose increased food intake without adverse effects and was selected for detailed analysis. Investigators then examined meal patterns, neuronal activation in the arcuate nucleus of the hypothalamus using Fos mapping, and neurochemical identity of activated neurons using RNAscope in situ hybridization. They also measured serum growth hormone (GH) levels. The study found that intranasal GHRP-6 increased food intake by raising both meal frequency and meal size. Fos expression in the arcuate nucleus was significantly elevated compared to saline controls, and activated neurons showed co-expression with GHSR, AgRP, and GHRH mRNA markers, implicating circuits involved in feeding and GH regulation. Serum GH levels were also elevated following intranasal GHRP-6. Limitations include exclusive use of a mouse model, a single species and sex are not specified, and the absence of human or pharmacokinetic data, meaning translation to clinical settings remains uncertain.
Endocrinology · Feb 2025DOI ↗ Review
This literature and patent review examines BPC 157 (Body Protection Compound 157), a synthetic pentadecapeptide derived from human gastric juice. The authors surveyed preclinical evidence across multiple disease models, including tissue injury, inflammatory bowel disease, and central nervous system disorders, cataloguing the compound's reported pleiotropic (wide-ranging) biological activities and proposed mechanisms of action. The review also assesses available toxicity and safety data, noting that relatively few side effects have been reported in preclinical settings. Regulatory context is highlighted: BPC 157 has not been approved by the FDA or equivalent global authorities, as no sufficient clinical trials in humans have been completed. The compound was temporarily listed by the World Anti-Doping Agency (WADA) in 2022 but is no longer on the banned list. The authors additionally map recent patent applications and granted patents to reflect growing commercial and research interest. A key limitation acknowledged throughout is that virtually all supporting evidence comes from animal and in vitro studies, meaning the translation of these findings to human health outcomes remains unestablished.
Pharmaceuticals (Basel, Switzerland) · Jan 2025DOI ↗ Insufficient
This entry corresponds to a withdrawn article originally submitted to the journal Current Neuropharmacology, investigating the use of the stable gastric pentadecapeptide BPC 157 as a potential therapy for severe electrolyte disturbances in rats. The article was retracted at the authors' own request, and the publisher (Bentham Science) provided no details regarding the specific findings, data, or conclusions of the original study. Because the full content of the paper is unavailable — replaced entirely by a withdrawal notice — no experimental methods, results, or conclusions can be evaluated or attributed to the study. The withdrawal notice also includes standard publisher boilerplate regarding submission conditions and plagiarism policy, but does not disclose the reason for withdrawal. As a result, this record cannot be used to draw any conclusions about BPC 157's effects on electrolyte disturbances. Researchers and educators should treat this citation as non-existent in the evidence base, as the underlying data and claims are no longer accessible or endorsed by the authors or publisher.
Current neuropharmacology · Jan 2025DOI ↗ Review
This review paper evaluates pharmacologic treatments for female sexual dysfunction (FSD), with a primary focus on hypoactive sexual desire disorder (HSDD). The authors examine the two FDA-approved medications for FSD — flibanserin (a daily oral serotonin/dopamine modulator) and bremelanotide (an on-demand injectable melanocortin receptor agonist) — alongside investigational therapies such as Lorexys (a bupropion/trazodone combination) and various testosterone-based treatments. The review synthesizes study outcomes and safety profiles for each agent, and offers clinical guidance on patient selection, diagnosis, expectation setting, side effect management, and patient education. The authors note that while FDA-approved options exist, their clinical uptake has been limited by modest effect sizes, side effect burdens, and barriers to access. Investigational therapies show early promise but require further clinical validation. A key limitation of this paper is its nature as a narrative review, meaning it does not pool data systematically and may be subject to selection bias in the studies included. It does not introduce new primary data.
Clinical obstetrics and gynecology · Jan 2025DOI ↗ Animal only
This rat study investigated whether the stable gastric pentadecapeptide BPC 157, administered orally, could promote reattachment of the quadriceps muscle to bone following surgical detachment in rats. The model involved both complete detachment of the rectus femoris muscle and partial detachment of the vastus muscles. Untreated control animals exhibited persistent healing failure, including impaired walking and permanent knee flexure across all observation time points (1 day through 90 days post-injury). In contrast, animals receiving oral BPC 157 (at two dose levels) showed consistent improvement across macro- and microscopic analysis, ultrasound, MRI, biomechanical testing, and functional walking assessments. The authors report that treated animals showed early muscle-to-bone approximation, elimination of leg contracture, and progressive tissue reorganization, including periosteal reactivation and mesenchymal cell proliferation by day 3, and well-organized cortical bone with mature, parallel-oriented muscle fibers by 3 months. Key limitations include exclusive use of an animal model with no human data, lack of blinding details, and relatively small group sizes typical of preclinical peptide research. The findings are attributed solely to the study authors and do not establish clinical efficacy or safety in humans.
Pharmaceutics · Jan 2025DOI ↗ Moderate · human
This paper reports a prespecified subgroup analysis from a phase 2 randomized controlled trial examining how sex and baseline BMI influenced the efficacy and safety of survodutide, a dual glucagon/GLP-1 receptor agonist, in adults without diabetes who had a BMI ≥27 kg/m². A total of 387 participants were randomized to one of four once-weekly subcutaneous survodutide doses or placebo over 46 weeks, which included a 20-week dose-escalation phase followed by a 26-week maintenance phase. The study found that, across survodutide-treated groups, females experienced greater reductions in both bodyweight and waist circumference compared with males. Participants who started with a lower baseline BMI showed proportionally greater bodyweight reductions, while those with a higher baseline BMI showed greater absolute reductions in waist circumference. Adverse event rates were broadly comparable across sex and BMI subgroups, with nausea being the most common gastrointestinal side effect reported in all subgroups. Key limitations include the descriptive (non-inferential) nature of the subgroup analyses, the relatively modest sample size when subdivided by subgroup, and potential confounding from COVID-19-related treatment discontinuations. These findings suggest differential responses by sex and baseline BMI, but the subgroup design limits causal conclusions.
Diabetes, obesity & metabolism · Jan 2025DOI ↗ Animal only
This study used female Syrian hamsters as an animal model to investigate how bremelanotide (Vyleesi), an FDA-approved drug for hypoactive sexual desire disorder (HSDD), affects the brain's reward system. Researchers examined melanocortin receptor (MC3R and MC4R) expression in the mesolimbic dopamine system — specifically the ventral tegmental area (VTA) and nucleus accumbens (NAc) — and assessed whether the drug enhanced sexual reward using a conditioned place preference (CPP) paradigm. Key findings attributed to the study include: MC4R mRNA was predominantly expressed in dopamine neurons in the VTA, while in the NAc and dorsal striatum, MC4R was rarely co-expressed with dopamine D1 or D2 receptor neurons, appearing instead in interneurons. Neither dose of bremelanotide tested altered melanocortin receptor mRNA expression in the mesolimbic system. Although sexual experience itself produced a CPP in female hamsters, bremelanotide did not enhance this sexual reward response. The authors conclude that bremelanotide does not appear to act through the VTA-NAc reward circuit in this model. A key limitation is that findings are derived entirely from an animal model and may not directly translate to human neurobiology or clinical outcomes.
Neuropharmacology · Jan 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 ↗ Review
This review paper examines the role of zonulin — a protein that regulates intestinal tight junctions (TJs) — in the pathogenesis of Chronic Inflammatory Disorders (CIDs). The authors explore how dysregulation of zonulin contributes to increased intestinal permeability ("leaky gut"), which may facilitate the translocation of harmful substances from the gut into the bloodstream, potentially driving or worsening conditions such as Inflammatory Bowel Disease (IBD), celiac disease, and Multiple Sclerosis (MS). The paper synthesizes preclinical and clinical research on larazotide acetate, a zonulin antagonist, highlighting its potential to improve gut barrier integrity and reduce inflammation in CID patients. The authors also discuss zonulin's promise as a biomarker for intestinal permeability. Key limitations acknowledged by the review include the need for further mechanistic clarification of zonulin antagonists and robust clinical trials to establish their efficacy and safety. As a narrative review, this paper does not generate new primary data, and its conclusions are dependent on the quality and consistency of the underlying studies it synthesizes. The authors call for continued research to inform personalized therapeutic strategies for CIDs.
Current medicinal chemistry · Jan 2025DOI ↗ Review
This review paper examines the current state of knowledge and methodology surrounding the skin permeation of GHK-Cu (glycyl-L-histidyl-L-lysine copper tripeptide), a naturally occurring cosmetically active compound (CAC) associated with properties such as reducing fine lines and wrinkles, improving skin elasticity, and tightening skin. The authors highlight a central challenge: GHK-Cu is relatively hydrophilic, which limits its ability to penetrate the lipophilic stratum corneum, the skin's outermost barrier. The paper reviews liposomal encapsulation as a strategy to improve GHK-Cu's skin permeation potential, and surveys existing methods used to study transdermal transport of CACs—both free and liposome-encapsulated. A key finding from the literature analysis is that research specifically examining liposome-mediated transport of GHK-Cu is sparse, representing a notable gap in the field. The authors argue this gap motivates further methodological development to better assess how liposomes affect GHK-Cu trafficking through skin layers. As a review, the paper synthesizes existing literature rather than presenting original experimental data, and it does not include clinical trials or controlled human studies. Its conclusions about efficacy are therefore inferential and limited by the quality and quantity of the underlying studies reviewed.
Molecules (Basel, Switzerland) · Jan 2025DOI ↗ In vitro
This study investigated whether ibutamoren (IBU) — a compound known primarily as a growth hormone secretagogue — might also act as an inhibitor of the MDM2-p53 interaction, a pathway dysregulated in roughly half of human cancers. MDM2 normally tags the tumour suppressor p53 for degradation; blocking this interaction is a recognized anticancer strategy. The researchers first used in silico molecular modelling to predict that IBU binds favorably to the p53-binding pocket of MDM2 and exhibits a low estimated IC50 for MDM2 inhibition. They then tested IBU on immortalized human cancer cell lines in vitro, finding reduced cell viability in lines with an intact, functional MDM2-p53 pathway but not in lines carrying damaging mutations in this pathway. RT-qPCR analysis supported this pattern, showing differential expression of two p53 target genes in wild-type but not mutant cell lines after IBU treatment. Key limitations include exclusive reliance on cell-line models (no animal or human data), use of immortalized rather than primary cells, and the preliminary, exploratory nature of the work. The authors conclude that IBU shows early-stage anticancer activity potentially mediated through the MDM2-p53 axis and warrants further mechanistic investigation.
Basic & clinical pharmacology & toxicology · Jan 2025DOI ↗ Insufficient
This cross-sectional pilot study examined the direct-to-consumer market for compounded glucagon-like peptide-1 (GLP-1) receptor agonists in Colorado. Researchers conducted Google searches of business websites advertising compounded GLP-1 products for weight loss across census-defined statistical areas between March and April 2024. They identified 93 websites corresponding to 188 physical locations. Most businesses were categorized as medical/health spas or weight loss services. Semaglutide was the most commonly advertised product (92/93 sites), followed by tirzepatide (40/93). Some sites advertised combination formulations including B vitamins, BPC-157 (flagged by the FDA as unsafe for compounding), and other additives. Seven sites advertised oral formulations. Notably, 41 of 93 websites referenced FDA approval in their product descriptions—a potentially misleading claim, as compounded products are not FDA-approved—and 5 sites incorrectly referred to products as "generic." The study's limitations include its focus on a single state, reliance on publicly available website data, and its pilot/cross-sectional design, which limits generalizability. The authors conclude that regulatory action is needed to address misleading advertising and safety concerns in this market.
Journal of pharmaceutical policy and practice · Dec 2024DOI ↗ 🧪 TrialInsufficient
Registered Phase 3 interventional trial (recruiting). The main purpose of this study is to evaluate additional dosing options for dulaglutide in pediatric participants with Type 2 Diabetes. Participation in this study will last about 8 months.
ClinicalTrials.gov · Dec 2024View trial ↗ 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 ↗ Moderate · human
This meta-analysis pooled data from 18 treatment arms across multiple randomized controlled trials (total n = 1,029 participants) to evaluate the effect of injectable survodutide — a dual glucagon and GLP-1 receptor agonist — on obesity-related outcomes. Searches were conducted across major databases through August 2024. Using a random-effects model, the authors found that survodutide was associated with statistically significant reductions in body weight (weighted mean difference: −8.33 kg), BMI (−4.03 kg/m²), and waist circumference (−6.33 cm) compared to control groups. Subgroup analyses suggested that longer intervention durations (more than 16 weeks) and higher doses were associated with greater reductions in weight and waist circumference, a pattern also supported by meta-regression. Key limitations include very high statistical heterogeneity for weight (I² = 99.6%) and waist circumference (I² = 99.5%), which may reflect substantial differences in study populations, doses, and durations across the included trials. The relatively small total participant count and the emerging nature of the evidence base for survodutide also limit the certainty of conclusions. The findings suggest a potential role for survodutide in weight management, but the high heterogeneity warrants cautious interpretation.
Diabetology & metabolic syndrome · Nov 2024DOI ↗ 🧪 TrialInsufficient
Registered Phase 3 interventional trial (active not recruiting). The main purpose of this study is to evaluate the efficacy and safety of retatrutide compared to tirzepatide in adults who have obesity. The study will last about 89 weeks.
ClinicalTrials.gov · Oct 2024View trial ↗ In vitro
This study presents a novel analytical application of capillary electrophoresis coupled to inductively coupled plasma tandem mass spectrometry (CE-ICP-MS/MS) to investigate the encapsulation of the copper tripeptide complex GHK-Cu within liposomes — a delivery system commonly used in cosmetic formulations. Using an ethanol injection method to form liposomes, the researchers monitored copper (Cu) and phosphorus (P) signals to confirm liposome formation and quantify the concentration of GHK-Cu encapsulated within them. The study demonstrates that CE-ICP-MS/MS, valued for its high sensitivity and ability to preserve analytes in their intact chemical form under mild, physiologically compatible conditions, can be successfully applied in cosmetic science contexts. The authors propose this methodology could support the development and optimization of diverse liposomal cosmetic formulations. Importantly, this paper is a methodological/analytical chemistry study — it does not test GHK-Cu efficacy in humans or animals, make clinical claims, or evaluate biological outcomes. Its findings are limited to demonstrating an analytical technique for characterizing a cosmetic ingredient's encapsulation efficiency in a laboratory setting.
Electrophoresis · Oct 2024DOI ↗