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 ↗ Review
This review examines the potential neuroprotective role of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) — a drug class established for managing type 2 diabetes and obesity — in the context of neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The authors propose that neurodegeneration is driven by a self-reinforcing cycle of chronic neuroinflammation and central metabolic dysfunction, worsened by impaired insulin/IGF-1 signalling, mitochondrial dysfunction, and pro-inflammatory microglial activation triggered by misfolded protein aggregates. The review synthesizes preclinical and clinical trial data to argue that GLP-1RAs may disrupt this cycle via a dual mechanism: reducing central insulin resistance and directly suppressing neuroinflammatory cascades by modulating glial responses, inhibiting pro-inflammatory cytokines, and reducing oxidative stress in the CNS. The authors conclude that GLP-1RAs represent a promising, translatable therapeutic strategy for neurodegeneration and call for large-scale human trials. Limitations include the review's reliance on synthesizing heterogeneous preclinical and early clinical data, without original data collection, and the mechanistic conclusions remain to be validated in robust, adequately powered human studies.
Diabetes, obesity & metabolism · Dec 2025DOI ↗ Review
This review examines sexual dysfunction as a sequela of breast and gynecologic cancer treatment, with a focus on genitourinary syndrome of menopause (GSM). The authors conducted a comprehensive literature search across PubMed, Google Scholar, and Scopus, covering peer-reviewed studies from the past 30 years. Findings were synthesized thematically, grouping studies by cancer type, treatment modality, and impact on sexual function. The review found that common symptoms—including vaginal dryness, dyspareunia, and diminished sexual desire—are frequently underrecognized. Nonhormonal management strategies identified included minimizing irritants, vaginal moisturizers, lubricants, dilators, and pelvic floor therapy. Local hormonal therapies were noted as potentially appropriate for select patients depending on cancer hormone-sensitivity status. For low sexual desire, pharmacological agents such as bremelanotide and flibanserin were reported to have demonstrated efficacy in the literature reviewed. The authors advise against vaginal laser treatments and compounded hormones in these populations due to safety concerns. A multidisciplinary approach involving gynecologic, psychological, and oncologic expertise was emphasized. Limitations include the absence of a formal quality assessment tool and reliance on narrative thematic synthesis rather than meta-analytic methods.
Journal of minimally invasive gynecology · Dec 2025DOI ↗ 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 ↗ Review
This review paper examines the relationship between aging and Thymosin Alpha-1 (Tα1), a peptide hormone naturally produced by the thymus gland. The authors describe how age-related thymic involution leads to reduced T-cell production, chronic low-grade inflammation (inflammaging), and heightened vulnerability to age-related diseases — a phenomenon collectively termed immunosenescence. The paper outlines Tα1's proposed mechanisms of action, including stimulation of T-cell differentiation, enhancement of thymic output, and modulation of dendritic cells and macrophages. It also highlights Tα1's immunomodulatory, anti-inflammatory, and antioxidant properties. The authors review preclinical and clinical evidence suggesting Tα1 may improve vaccine responses in elderly populations and help counteract immunosenescence. Additionally, the paper discusses Refnot, a hybrid fusion drug combining Tα1 with tumor necrosis factor alpha (TNFα), which reportedly retains antitumor activity while exhibiting reduced toxicity compared to TNFα alone. The authors conclude that Tα1 holds therapeutic promise for age-related immune dysfunction but emphasize that long-term efficacy and safety data in geriatric populations remain limited and that further research is warranted. As a review, this paper synthesizes existing literature rather than presenting original experimental data.
International journal of molecular sciences · Nov 2025DOI ↗ Review
This review article examines the evolving landscape of engineered nutrient-stimulated hormonal (NUSH) peptide therapies for obesity and related metabolic conditions, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular disease. The authors describe the mechanistic basis of GLP-1 receptor agonists (GLP-1RAs) and their limitations as monotherapies, then explore how dual and triple co-agonist strategies — combining GLP-1 with GIP, glucagon, amylin, or peptide YY — aim to overcome those gaps. The review highlights clinical and preclinical data for specific agents: tirzepatide (GLP-1/GIP), CagriSema (GLP-1/amylin), and retatrutide (GLP-1/GIP/glucagon), noting reported benefits in weight reduction, glycemic control, liver health, cardiovascular outcomes, and inflammation. The paper also discusses non-peptidyl oral GLP-1 RAs such as orforglipron as adherence-improving alternatives. The authors frame these multi-agonist therapies as a paradigm shift analogous to the pleiotropic hormonal effects of bariatric surgery, and as building blocks for precision metabolic medicine. As a narrative review, it does not generate new primary data, and conclusions depend on the quality and heterogeneity of the underlying cited studies.
Clinical and molecular hepatology · Nov 2025DOI ↗ Review
This narrative review examines the current and emerging landscape of GLP-1 receptor agonists (GLP-1RAs) as treatments for obesity and related metabolic conditions. The authors survey the three FDA-approved agents for obesity—liraglutide, semaglutide, and tirzepatide—alongside off-label options, summarizing evidence for their efficacy in weight reduction and glycemic control. The review also discusses expanding indications, including potential benefits in neurodegenerative disorders, fatty liver disease, dyslipidemia, atherosclerosis, cardiovascular disease, chronic kidney disease, and heart failure. Emerging pipeline agents—such as CagriSema, orforglipron, mazdutide, retatrutide, and survodutide—are highlighted alongside innovations like ultralong-acting formulations, combination therapies, higher-dose oral delivery, and AI-integrated drug development. The authors note that generic liraglutide and evolving insurance coverage may reshape affordability and access. Key limitations acknowledged include adherence challenges, safety concerns, disparities in global access, and the need for long-term data on sustained weight loss and disease modification. As a narrative review, the paper synthesizes existing literature rather than generating new primary data, and conclusions are therefore subject to the quality and selection of included studies.
Journal of obesity · Nov 2025DOI ↗ Review
This scoping review examines the biological rationale and existing evidence for using glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the management of psoriatic disease (PsD), a chronic systemic inflammatory condition frequently accompanied by cardiometabolic comorbidities such as obesity, type 2 diabetes mellitus, and cardiovascular disease. The authors explored three main areas: (1) how obesity, diabetes, and cardiovascular disease influence PsD severity and treatment resistance; (2) the established efficacy of GLP-1RAs in managing these comorbidities; and (3) early evidence from rheumatologic and dermatologic conditions including rheumatoid arthritis, osteoarthritis, osteoporosis, psoriasis, and hidradenitis suppurativa. The review highlights shared immunopathogenic mechanisms — particularly Th1/Th17-driven cytokines such as TNF, IL-6, and IL-17 — as a rationale for GLP-1RA use beyond metabolic indications. The authors report that early clinical and preclinical data suggest GLP-1RAs may reduce systemic inflammation and PsD burden, but acknowledge this evidence is preliminary. Key limitations include the scoping review design (which maps available evidence rather than synthesizes effect sizes), reliance on preclinical and indirect data, and the absence of dedicated randomized controlled trials in PsD populations. The authors conclude that further clinical trials are needed to establish disease-modifying potential.
Inflammation research : official journal of the European Histamine Research Society ... [et al.] · Nov 2025DOI ↗ Review
This paper examines the socioeconomic and systemic barriers that limit equitable access to glucagon-like peptide-1 (GLP-1) receptor agonist medications as obesity treatments. The authors note that obesity disproportionately burdens socioeconomically disadvantaged populations, yet the high cost and limited supply of GLP-1 agonists mean these effective therapies remain largely accessible only to those who can afford to pay privately. The paper frames this disparity through Julian Tudor Hart's "inverse care law," which describes how access to effective healthcare tends to be inversely correlated with clinical need. The authors argue that current rollout patterns risk deepening existing health inequalities rather than alleviating them. They call for evidence-informed policies to prioritize access based on clinical need, equitable global distribution strategies, and complementary investment in preventive and population-level public health measures. As a narrative review and commentary, the paper does not present original clinical data or trial results, and its conclusions are based on synthesized existing evidence and policy analysis rather than empirical study. Its primary value is as a framework for health policy discussion around GLP-1 access equity.
Review
This review synthesizes current scientific understanding of ghrelin, a hormone originally characterized primarily for its role in appetite stimulation and growth hormone release. The authors trace the full arc of ghrelin biology: from its biosynthesis (preproghrelin processing and O-acylation by the enzyme GOAT to produce the active acyl-ghrelin form), through its receptor pharmacology at GHSR1a, to its wide-ranging physiological roles. The review highlights that des-acyl ghrelin—the predominant circulating form—can exert effects independently of or with lower potency at GHSR1a, and that truncated "mini-ghrelins" may act as competitive antagonists. Recent cryo-EM structural data on GHSR1a are discussed as a framework for understanding biased signaling and drug design. The authors also review ghrelin's roles in glucose regulation, gastric function, cardiovascular tone, bone remodeling, renal hemodynamics, innate immunity, and the central nervous system—including links to neuroprotection, depression, Alzheimer's disease, and addiction. Translational topics covered include ghrelin stabilization strategies, synthetic ligands (agonists, antagonists, inverse agonists), LEAP-2-based approaches, and GOAT inhibitors. As a narrative review, the paper does not generate new experimental data, so primary evidence quality depends on the underlying cited studies.
International journal of molecular sciences · Nov 2025DOI ↗ Review
This narrative review synthesizes the current landscape of FDA-approved and investigational pharmacotherapies for obesity management. The authors examine six approved long-term agents — orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, semaglutide, and tirzepatide — covering their mechanisms of action, pivotal efficacy data, safety profiles, indications, and prescribing considerations. The review notes that semaglutide and tirzepatide have substantially raised expectations for pharmacological weight loss compared to older agents. Emerging investigational compounds, including oral GLP-1 receptor agonists such as orforglipron and multireceptor agonists such as retatrutide, are highlighted as showing even greater early-phase efficacy signals. Common safety considerations discussed include gastrointestinal adverse effects, gallbladder events, pancreatitis risk, thyroid C-cell tumor warnings, teratogenicity, and cost and access barriers. The authors emphasize that patient selection should be guided by BMI, comorbidities, and contraindications. Key limitations acknowledged by the review include a lack of direct head-to-head comparative trials, limited long-term cardiovascular outcomes data, and questions about weight durability after treatment discontinuation. The authors identify these gaps as priorities for future research.
Review
This review paper surveys the current landscape of obesity pharmacotherapy, covering both approved and emerging treatment options. The authors outline the clinical burden of obesity, noting its associations with diabetes, cardiovascular disease, hypertension, and hyperlipidemia, and briefly describe non-pharmacological management strategies such as nutritional therapy and exercise. The review catalogues FDA-approved anti-obesity medications — orlistat, setmelanotide, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, and tirzepatide — and highlights semaglutide as having a favorable clinical and regulatory profile. Emerging agents discussed include orforglipron, a non-peptide oral GLP-1 receptor agonist positioned as a potentially convenient alternative to injectable therapies. The authors also explore adjunctive approaches such as probiotics, prebiotics, fecal microbiota transplantation, and mitochondrial uncouplers. Key barriers to obesity management — including financial constraints, inadequate clinician training, and lack of reimbursement — are identified. The paper concludes by advocating for innovative, multidisciplinary, and patient-centered care models. As a narrative review, the paper does not generate new primary data, and conclusions reflect the authors' synthesis of existing literature rather than independent experimental findings.
Review
This review examines the role of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) in kidney protection among people living with type 2 diabetes and obesity. The authors trace the evolution of GLP-1 research from its original characterization as a metabolic hormone—regulating insulin secretion, suppressing glucagon, and reducing insulin resistance partly through weight loss—toward a broader understanding of its effects on kidney physiology and clinical outcomes. The review summarizes preclinical data alongside landmark clinical trial findings, noting that renoprotective effects have been observed despite only modest GLP-1 receptor expression in the kidney. Key clinical outcomes discussed include changes in albuminuria, estimated glomerular filtration rate decline, and cardiovascular-renal endpoints drawn from large outcomes trials. The authors frame GLP-1 RAs as an area of intensive ongoing investigation for chronic kidney disease management in the relevant patient population. As a narrative review, this paper does not conduct original data collection or meta-analysis, and conclusions are therefore subject to the selection and interpretation choices of the authors. It provides a useful synthesis of the existing evidence base but does not itself constitute primary clinical trial data.
The Journal of clinical investigation · Nov 2025DOI ↗ Review
This review examines the relationship between glucagon-like peptide-1 (GLP-1) receptor agonists — a class of drugs used to treat obesity and type 2 diabetes — and cancer risk. The authors note that obesity and type 2 diabetes are established risk factors for several cancers, and that GLP-1 receptor agonists have become transformative treatments for these conditions. The review synthesizes current clinical evidence across multiple cancer types, including thyroid, pancreatic, gastrointestinal, and hormone-dependent malignancies. The authors report that recent meta-analyses generally do not support an increased cancer incidence with GLP-1 receptor agonist use, and suggest a potential risk-lowering effect in some cancer types. Preclinical studies are also discussed, with findings pointing to possible anticancer mechanisms even in non-obese models, including immune-modulating effects that may reflect direct action on immune cells or stem from improved metabolic function. The review highlights ongoing clinical trials and identifies key gaps in translational research, including questions about treatment timing, duration, concurrent anticancer therapies, and the distinction between cancer risk versus progression models. As a narrative review, it does not generate new primary data, and conclusions depend on the quality of the underlying studies reviewed.
The Journal of clinical investigation · Nov 2025DOI ↗ Review
This narrative review examines pharmacologic management of vasomotor symptoms (VMS) and decreased libido in breast cancer patients receiving endocrine therapy — a population that commonly experiences new or worsened menopausal symptoms. The authors searched PubMed, Cochrane Library, and Web of Science to summarize established agents (SSRIs, SNRIs, gabapentin, clonidine) and highlight emerging therapies: fezolinetant and elinzanetant (neurokinin 3 receptor antagonists for VMS), and flibanserin and bremelanotide (serotonin/dopaminergic modulator and melanocortin receptor agonist, respectively, for low libido). The review notes that existing options provide inadequate symptom relief, representing a meaningful therapeutic gap. Crucially, the authors emphasize that clinical trials supporting these novel agents explicitly excluded breast cancer patients, meaning their safety and efficacy in this population remain unestablished. The paper aims to equip clinicians with practical considerations for weighing these therapies in breast cancer patients while awaiting dedicated research. Key limitations include the review format, reliance on trials conducted in the general population, and the absence of breast cancer-specific clinical data for the highlighted novel agents.
Expert review of clinical pharmacology · Oct 2025DOI ↗ Review
This review paper examines the potential role of nutrient-stimulated hormone-based therapies (NuSHs) — particularly GLP-1 receptor agonists — in the prevention and management of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC). The authors contextualize MASH as the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), which is now the most prevalent chronic liver disease in Western populations. The review synthesizes emerging clinical and preclinical evidence suggesting that NuSHs can resolve MASH without worsening fibrosis, primarily through weight loss and improved insulin sensitivity. However, the authors note that benefits appear less pronounced in cirrhotic patients, implying greater utility in early disease stages. Preclinical models suggest NuSHs may reduce MASH-related HCC incidence and tumor burden through systemic metabolic improvements rather than direct anti-cancer mechanisms. Observational data from bariatric surgery populations further support a preventive role for weight loss. The authors also propose that integrating NuSHs into post-locoregional HCC treatment pathways could delay systemic therapy, improve immunotherapy synergy, and enhance transplant eligibility. Key limitations include the indirect nature of evidence, inconsistent fibrosis regression data, and an absence of trials with oncological primary endpoints.
Journal of clinical and translational hepatology · Oct 2025DOI ↗ Review
This comprehensive review synthesizes research published between 2016 and 2025 on the role of tripeptides in wound healing and skin regeneration. The authors examine how these short, three-amino-acid peptides regulate critical repair processes including cell migration, proliferation, and differentiation, as well as inflammation modulation, angiogenesis promotion, and extracellular matrix (ECM) remodeling. The review highlights several specific tripeptides: GHK-based formulations (including nanoparticle conjugates, hydrogels, and clinical derivatives TriHex and TriHex 2.0) were found in cited studies to enhance fibroblast migration, collagen and elastin synthesis, ECM remodeling, and wound closure with added antimicrobial activity. KdPT was reported to mitigate hyperglycemia-induced oxidative stress and restore keratinocyte function, while KPV-loaded hydrogels reduced inflammation and combated MRSA infections. Lipotripeptides (DICAMs) were noted to inhibit and disrupt bacterial biofilms, and GPE was associated with neuroprotection via ERK and PI3K/Akt signaling. The review also addresses physicochemical comparisons with larger peptides, biomaterial scaffold integration, and emerging applications in cancer and cosmetics. As a narrative review, it does not generate new experimental data. Key limitations include inherent selection bias and the predominance of preclinical evidence in the underlying literature. The authors call for further research into stability, bioavailability, and delivery optimization.
International journal of medical sciences · Oct 2025DOI ↗ Review
This updated narrative review examines the efficacy and safety of anti-obesity medications (AOMs) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH). The authors synthesize evidence on several pharmacologic classes, with particular focus on incretin-based therapies. GLP-1 receptor agonists, specifically liraglutide and semaglutide, are reported to reduce hepatic steatosis, improve liver enzyme profiles, and attenuate fibrosis progression. Tirzepatide, a dual GLP-1/GIP agonist, is noted to produce superior weight loss compared to GLP-1 monotherapy, though data on hepatic histological outcomes in MASLD/MASH remain limited. Retatrutide, a triple GLP-1/GIP/glucagon agonist, showed the most pronounced metabolic effects overall, but its liver-specific histological impact is described as underexplored. The review also flags safety concerns with other AOMs such as bupropion-naltrexone and phentermine-topiramate, citing potential hepatotoxicity risks. The authors note that advanced MASLD may alter drug pharmacokinetics, complicating treatment decisions. Key limitations include the review's narrative design, heterogeneity of cited primary studies, and a general lack of large-scale, liver-histology-focused trials for newer agents.
World journal of gastroenterology · Oct 2025DOI ↗ Review
This article is a regulatory milestone review summarizing the development history of mazdutide (Xinermei®), a dual glucagon receptor (GcgR) and glucagon-like peptide-1 receptor (GLP-1R) agonist co-developed by Eli Lilly and Innovent Biologics. The review traces the compound's path to its first regulatory approval in China in June 2025 for long-term body weight management in adults with obesity (BMI ≥28 kg/m²) or overweight with comorbidities (BMI ≥24 kg/m²), alongside diet and physical activity. A subsequent Chinese approval for glycemic control in type 2 diabetes followed in September 2025. The article also notes ongoing clinical investigations into metabolic dysfunction-associated fatty liver disease, obstructive sleep apnea, and alcohol use disorder. As a "First Approval" narrative review, it consolidates developmental milestones rather than presenting original trial data. It does not independently report clinical outcomes, efficacy effect sizes, or safety data from primary studies, limiting the ability to assess the strength of underlying evidence directly from this article alone.
Review
This review examines the expanding cardiovascular applications of glucagon-like peptide-1 (GLP-1) receptor agonists, a class of peptide-based agents originally developed for type 2 diabetes management. The authors synthesize molecular mechanistic data alongside clinical evidence from major cardiovascular outcome trials (CVOTs) to characterize how GLP-1 agonists may reduce risk across conditions including atherosclerosis, heart failure, stroke, and vascular dementia. Proposed mechanisms discussed include anti-inflammatory, anti-atherogenic, endothelial-protective, and direct cardioprotective effects. The review highlights findings from multiple CVOTs reporting reductions in major adverse cardiovascular events (MACEs), myocardial infarction, stroke, and cardiovascular mortality. Notably, the SELECT trial is cited as evidence extending potential benefit to non-diabetic individuals with obesity and established CVD. The review also addresses emerging dual GLP-1/GIP agonists such as tirzepatide and its own CVOT data. The authors acknowledge important limitations, including high drug costs, unresolved long-term safety questions, and real-world implementation barriers. As a narrative review, this paper does not generate primary data and is subject to the inherent risk of selective literature synthesis. It provides a useful conceptual overview but does not independently establish causality or efficacy.
Journal of clinical medicine · Sep 2025DOI ↗