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 ↗ 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 ↗ 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 ↗ Insufficient
SYNCHRONIZE-CVOT is a phase 3, randomized, double-blind, placebo-controlled, event-driven cardiovascular (CV) outcomes trial evaluating survodutide — a dual glucagon and GLP-1 receptor agonist administered subcutaneously once weekly — in adults with obesity or overweight (BMI ≥27 kg/m²) who also have established CV disease, chronic kidney disease, and/or at least two weight-related complications or CV risk factors. The primary endpoint is time to first occurrence of a 5-point major adverse cardiovascular event (MACE) composite. The trial targets enrollment of 4,935 participants globally and is currently in the recruitment phase (NCT06077864). The paper describes the scientific rationale — that dual glucagon/GLP-1 receptor agonism may produce greater weight reduction than GLP-1 agonism alone — and outlines the trial design in detail. As a design/rationale publication, no efficacy or safety outcomes are yet available. Key limitations at this stage include the absence of results and the event-driven nature meaning the timeline is uncertain. This trial will be the first to formally assess CV safety and potential efficacy of survodutide in a high-risk obesity population.
JACC. Heart failure · Oct 2024DOI ↗ Animal only
This animal study investigated whether two synthetic analogs of the ACTH(4-10) peptide fragment — Semax (ACTH(4-7)-Pro-Gly-Pro) and Melanotan II (MTII), a melanocortin receptor agonist — possess antidepressant-like and antistress properties in a chronic unpredictable stress (CUS) rat model of depression. Male adult Sprague-Dawley rats were subjected to CUS and received daily intraperitoneal injections of either saline or a low dose of Semax or MTII. Outcomes assessed included body weight, hedonic status via the sucrose preference test, adrenal gland weight, hippocampal BDNF levels, and immobility in the forced swim test. The study found that both Semax and MTII reversed or substantially reduced CUS-induced anhedonia, suppressed body weight gain, adrenal hypertrophy, and decreased hippocampal BDNF levels. Neither the CUS procedure nor the peptide treatments produced significant effects on immobility in the forced swim test. The authors concluded that systemically administered ACTH(4-10) analogs may have therapeutic potential for depression and stress-related conditions. Key limitations include the exclusive use of male rats, an animal-only design with no human data, and restriction to a single dose level.
European journal of pharmacology · Oct 2024DOI ↗ Animal only
This study investigated whether the naturally occurring copper-binding peptide GHK-Cu (glycyl-L-histidyl-L-lysine copper complex) could reduce Alzheimer's disease (AD)-related pathology in a transgenic mouse model. Male and female 5xFAD mice — a well-established preclinical model of AD — were treated with intranasal GHK-Cu three times per week from 4 to 7 months of age, with a C57BL/6J background strain as context. The researchers assessed behavioral outcomes, amyloid plaque burden, and neuroinflammation markers. The study found that treated mice showed delayed cognitive impairment compared to untreated controls, along with reductions in amyloid plaques and lower levels of MCP1-associated inflammation in the frontal cortex and hippocampus. The authors suggest these findings justify further investigation of GHK-Cu as a potential AD therapeutic. Key limitations include the exclusively preclinical (animal) nature of the work — results in transgenic mouse models do not reliably predict outcomes in humans — and the fact that 5xFAD mice represent an aggressive, artificially accelerated form of amyloid pathology that may not fully reflect the complexity of human AD.
Aging pathobiology and therapeutics · Sep 2024DOI ↗ Insufficient
This forensic laboratory study describes the analytical challenges encountered when identifying Melanotan II — a synthetic peptide informally nicknamed the "Barbie drug" — in suspected illicit drug samples submitted for analysis. Researchers used HPLC-DAD, UHPLC-TOF-MS, and UPLC-MS/MS to characterize a powder found in pharmaceutical-appearing vials labeled "Melanotan II." Standard library searches via HPLC-DAD yielded no match, partly because the UV spectrum for Melanotan II was not available in the reference library at the time. Mass spectrometric identification was further complicated by the peptide's relatively high molecular weight (~1024 Da), which exceeded the typical detection ceiling of instruments configured for classical small-molecule drugs of abuse, and by the compound's multi-charged ionization behavior. Using a reference standard, the team ultimately confirmed the identity of Melanotan II and estimated a purity of approximately 30%. The study highlights that Melanotan II is not approved for market use due to safety concerns and is sold illicitly primarily for skin tanning. The authors suggest that the significant analytical hurdles involved in detecting this peptide may partly explain its growing presence on the illicit market. This study is a descriptive forensic case report with no clinical outcome data or human subject testing.
Journal of forensic sciences · Sep 2024DOI ↗ Review
This review article provides a comprehensive overview of approved and emerging hormone-based anti-obesity medications (AOMs), situating them within the broader context of obesity as a complex, chronic, global disease. The authors summarize the current regulatory landscape, noting that the GLP-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide have received FDA and EMA approval for weight management. The review also covers pipeline agents, including oral GLP-1RAs (semaglutide, danuglipron, orforglipron), the amylin receptor agonist cagrilintide (alone and in combination with semaglutide), and dual agonists such as tirzepatide (GIP/GLP-1), survodutide, mazdutide, and pemvidutide (GLP-1R/GCGR). The authors highlight tirzepatide's placebo-subtracted weight reduction of 17.8% in a 72-week RCT and retatrutide's (a GLP-1R/GCGR/GIPR tri-agonist) placebo-subtracted reduction of 22.1% in a 48-week phase-II trial. The review cautions that long-term safety and cardiovascular outcome data for many of these agents remain incomplete. As a narrative review, it does not conduct original research or meta-analysis, and conclusions are limited by the quality and heterogeneity of the underlying primary studies it synthesizes.
Indian journal of endocrinology and metabolism · Sep 2024DOI ↗ Moderate · human
This systematic review and meta-analysis examined the weight-loss efficacy and safety of cagrilintide (an amylin analogue) alone and in combination with semaglutide 2.4 mg (referred to as "Cagrisema") compared to placebo or active comparators (semaglutide or liraglutide) in adults with obesity. Researchers searched electronic databases and identified 3 eligible randomized controlled trials encompassing 430 participants. The pooled analysis found that Cagrisema was associated with significantly greater percentage and absolute body weight reduction compared to semaglutide 2.4 mg alone over 20–32 weeks, though with notably high statistical heterogeneity (I² up to 98%). Cagrilintide monotherapy showed statistically similar weight loss to semaglutide or liraglutide over 26–32 weeks. Regarding safety, treatment-emergent and serious adverse events were broadly comparable across groups; however, gastrointestinal adverse events and vomiting were significantly more frequent with Cagrisema versus semaglutide, while vomiting was significantly lower with cagrilintide monotherapy versus semaglutide or liraglutide. Key limitations include the very small number of included trials (n=3), limited total sample size, short-to-medium follow-up durations, and very high heterogeneity, which tempers confidence in the pooled estimates.
Indian journal of endocrinology and metabolism · Sep 2024DOI ↗ Review
This review paper examines the history, development, and scientific utility of key synthetic tool compounds used to study the melanocortin receptor (MCR) family — a group of five Class A G protein-coupled receptors (GPCRs) involved in diverse physiological processes including pigmentation, steroidogenesis, and energy homeostasis. The authors trace how synthetic derivatives of the endogenous agonist α-MSH, including NDP-MSH (melanotan I), melanotan II (MTII), and SHU9119, have become essential pharmacological tools for the field. The review discusses how these compounds are used to validate cell lines stably expressing melanocortin receptors, serve as reference ligands in high-throughput screening, inform structure-activity relationship (SAR) studies, and act as core ligands in cryo-EM structural investigations of active and inactive receptor complexes. The paper also notes that these tool compounds have served as scaffolds for FDA-approved drugs. Limitations of the review include its descriptive, non-experimental nature and its focus on synthesizing existing literature rather than presenting new empirical data. It provides important context for researchers working on MCR pharmacology but does not itself generate clinical or mechanistic evidence.
ACS pharmacology & translational science · Aug 2024DOI ↗ Animal only
This review paper examines the published preclinical evidence on stable gastric pentadecapeptide BPC 157 as a potential therapeutic agent for intestinal anastomoses and related gastrointestinal conditions in rat models. The authors summarize findings across a range of anastomosis types — including esophagogastric, colocolonic, jejunoileal, and ileoileal — and report that BPC 157 therapy was associated with improved healing outcomes in these animal studies. The review also covers concomitant gastrointestinal disturbances such as esophagitis, sphincter dysfunction, colitis, short bowel syndrome, and major vessel occlusion, as well as dysfunction of the nitric oxide and prostaglandin systems. Additionally, the authors discuss fistula healing (e.g., colocutaneous, gastrocutaneous, vesicovaginal, rectovaginal) as a related phenomenon, framing fistulas as abnormal anastomoses between tissues. The review concludes that both anastomoses and fistulas showed healing responses attributed to BPC 157 in rat models. Limitations include the exclusive reliance on animal data, absence of human clinical trials, and the inherent interpretive limitations of a narrative review format. No controlled human evidence is presented or discussed.
Pharmaceuticals (Basel, Switzerland) · Aug 2024DOI ↗