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Neuroendocrine signature of ME/CFS: Meta-analytic evidence for bioactive cortisol deficit and exaggerated feedback sensitivity.

Mol Psychiatry

Tae-Wook Woo, Yu-Jin Choi, Jun-Yeol Kim +2 more

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a major clinical challenge as a complex multisystemic disorder with no well-established pathophysiological mechanism, characterized by persistent fatigue and post-exertional malaise, along with unrefreshing sleep, cognitive impairment, and impaired stress recovery. Despite decades of investigation into the hypothalamic-pituitary-adrenal (HPA) axis, a definitive neuroendocrine hallmark has remained elusive due to inconsistent findings across various cortisol matrices. Therefore, this systematic review and meta-analysis aimed to provide an integrated understanding of HPA-axis regulation in ME/CFS. We identified 46 case-control studies (comprising 46 independent datasets, including 12 pharmacological challenge studies), involving 1388 ME/CFS patients (71.9% female; mean age 37.3 ± 6.2 years) and 1349 matched healthy controls. Meta-analyses showed lower salivary cortisol at awakening and in the morning. Reductions were also observed in 24-h urinary cortisol and hair cortisol. In pharmacological challenge tests, patients exhibited impaired cortisol release in response to adrenocorticotropic hormone (ACTH) stimulation and exaggerated suppression following glucocorticoid administration. Collectively, these alterations indicate reduced free cortisol availability and enhanced HPA-axis negative feedback sensitivity, consistent with a hyporeactive endocrine state in ME/CFS. This neuroendocrine hypo-reactivity may underlie hallmark clinical features such as unrefreshing sleep, post-exertional malaise, and severe fatigue, as well as cognitive slowing, emotional blunting, and diminished stress resilience frequently observed in ME/CFS and related functional disorders. Integrating neuroendocrine and psychological perspectives may help clarify mechanisms of chronic stress maladaptation and inform psychobiological interventions for fatigue syndromes.

Early GH therapy and neurodevelopmental outcome in a child with compound heterozygous IGF1R variants.

JCEM Case Rep

Mariana Sá Pinto, Mariana Oliveira, Tomás Ferrão +3 more

Causal variants in the IGF 1 receptor (IGF1R) gene are associated with variable degrees of growth and neurodevelopmental impairment. While heterozygous variants often manifest as less severe phenotypes, homozygous loss-of-function mutations are widely regarded as incompatible with life. Biallelic hypomorphic variants are exceptionally rare and their clinical spectrum remains poorly defined. We report the case of a girl born at term after severe symmetric fetal growth restriction (FGR), identified prenatally through trio whole-exome sequencing as carrying compound heterozygous IGF1R variants-c.155G>C (p.Cys52Ser) and c.3476A>G (p.Asp1159Gly). Postnatally, she exhibited microcephaly, dysmorphic features, and marked growth failure. Growth hormone therapy was initiated at 13 months of age, leading to gradual and sustained improvement in head circumference, linear growth, and psychomotor development. We report a rare case of a prenatal diagnosis of compound heterozygous IGF1R variants with early GH treatment. The case broadens current knowledge on IGF1R-related disorders, shows that survival is possible in compound heterozygous states, and suggests a potential benefit of early GH therapy.

Single cell analysis of muscle contracture in cerebral palsy reveals pro-fibrotic and anti-myogenic stem cell populations with altered cell-cell interactions.

Am J Physiol Cell Physiol

Madison Stewart, Lin-Ya Hu, Taryn Loomis +8 more

Development of muscle contractures are common in cerebral palsy (CP) and characterized by high muscle stiffness that limits function and mobility. However, the state of stem cells within contracture, particularly muscle stem cells and fibro-adipogenic progenitors, are largely unknown. This study leverages single cell RNA sequencing technology to determine how specific cell types are altered in the contracture environment. Skeletal muscle biopsies were collected from children with CP or typically developing (TD) children undergoing surgery. The 10X Genomics platform was used on tissue from n=3 patients per condition. Significant changes in CP compared to TD were investigated within individual cell types for differentially expressed genes, gene ontologies, cell subpopulations and predicted interactions. CP muscle stem cells demonstrated significant upregulation of fibrotic genes and down regulation of myogenic genes compared to typically developing. Fibro-adipogenic progenitors in CP showed the emergence of a significant proportion of a highly profibrotic subpopulation, leading to the most dramatically up-regulated genes in CP also being extracellular matrix constituents. Interacting signals between fibro-adipogenic progenitors, muscle stem cells, and immune cells were identified that support contracture progression. Contracture reduces myogenic muscle stem cells and enhances fibrotic signals in muscle stem cells and fibro-adipogenic progenitors that perpetuate contracture. The study reveals specific genes and signaling pathways as therapeutic targets to reduce muscle contracture in children with CP.

Differential effects of human fibromyalgia sera on murine satellite glial cells: comment on the article by Mercado et al.

Clin Exp Rheumatol

Suhail Aamar, Emil Aamar

Liver benefits of early initiation of low-dose GLP-1 receptor agonists in newly diagnosed type 2 diabetes - A case report.

J Family Med Prim Care

Joyce Y Lee, Huy Nguyen, Tan Nguyen

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to exert favorable effects on hepatic biomarkers and liver-related conditions, including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. However, the optimal dosage and duration of GLP-1RA therapy necessary to achieve these extrapancreatic hepatic benefits remain unclear. In this case report, we presented a 28-year-old White Hispanic female with Class I obesity and newly diagnosed type 2 diabetes who demonstrated a marked and rapid normalization of persistently elevated alanine aminotransferase levels following the initiation of subcutaneous semaglutide therapy. This case report highlighted the potential for immediate hepatic improvement with GLP-1RA treatment, exceeding commonly anticipated clinical outcomes in primary care.

Efficacy, Safety and PK of Once-Daily Oral Semaglutide 25 mg for Obesity With and Without Type 2 Diabetes in Comparison With Subcutaneous Semaglutide 2.4 mg: A Model-Informed Drug Development Approach.

Diabetes Obes Metab

Rune Viig Overgaard, Oscar Birkhan, Naveen Rathor +4 more

Semaglutide has previously been approved for weight management and cardiovascular disease as a subcutaneous formulation, and more recently also as an oral formulation. However, there is limited information across oral dose levels, and there are no studies for the 25 mg dose in people with obesity and type 2 diabetes (T2D). To fulfil health authority approval requirements, population pharmacokinetic and exposure-response analyses were used to extrapolate efficacy and safety data from subcutaneous to oral semaglutide.

Enhancing economic modelling in obesity: integrating novel type 2 diabetes progression & obstructive sleep apnea remission - a UK case study.

J Med Econ

Lieven Annemans, Erin Johansson, Erik Spaepen +4 more

This study presents an updated health economic model for evaluating the long-term cost-effectiveness of interventions in overweight and obesity, integrating new clinical evidence from the SURMOUNT clinical trial programme and methodological advancements in type-2 diabetes and obstructive sleep apnea (OSA) modelling.

Therapeutic peptides in gerontology: mechanisms and applications for healthy aging.

Front Aging

Volodymyr Mavrych, Inna Shypilova, Olena Bolgova

Peptide therapeutics represent an emerging frontier in gerontological medicine, targeting fundamental hallmarks of aging including metabolic dysfunction, telomere attrition, tissue repair impairment, and hormonal decline.

Glymphatic System Dysfunction in Epilepsy: Clinical and Translational Perspectives.

Epilepsy Curr

Dong Ah Lee, Ho-Joon Lee, Kang Min Park

Epilepsy has traditionally been viewed as a disorder involving neuronal hyperexcitability and brain network dysfunction. However, growing evidence indicates that recurrent seizures are associated with widespread disturbances in brain homeostasis, including metabolic stress, neuroinflammation, vascular dysregulation, and sleep disruption. These processes extend beyond neurons and involve brain-wide clearance mechanisms that have received limited attention in epilepsy research. The glymphatic system is a specialized pathway that facilitates cerebrospinal fluid-interstitial fluid exchange and promotes the clearance of metabolic waste and neurotoxic solutes from the brain. Glymphatic transport depends on astrocytic aquaporin-4 channels and is strongly modulated by sleep-wake state, which is highly relevant to epilepsy given the close bidirectional relationship between seizures and sleep disturbances. Impaired glymphatic clearance has been linked to protein accumulation, neuroinflammation, and cognitive decline during aging and in neurodegenerative diseases, suggesting that similar mechanisms may contribute to epilepsy-related disease progression. In this review, we summarize current knowledge of glymphatic anatomy and physiology, focusing on advances in neuroimaging. We then synthesize emerging evidence demonstrating glymphatic dysfunction across multiple epilepsy syndromes. We discuss the clinical implications of impaired cerebral waste clearance for disease burden, treatment outcomes, and cognitive dysfunction and highlight potential therapeutic strategies aimed at modulating glymphatic function. Finally, we address the ongoing debates regarding glymphatic mechanisms, imaging biomarkers, and causal relationships in epilepsy. Collectively, the available data suggest that glymphatic system dysfunction represents a system-level abnormality in epilepsy, offering a complementary framework that integrates the metabolic, vascular, and sleep-related aspects of epileptic brain dysfunction.

Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline.

Naunyn Schmiedebergs Arch Pharmacol

Ayman Ali Mohammed Alameen, Hayder M Al-Kuraishy, Mohamed N Fawzy +1 more

Cellular senescence, driven by the interaction between FOXO4 and p53, is increasingly recognized as a crucial mechanism in brain aging and the development of neurodegenerative disorders. The senolytic peptide FOXO4-DRI, which has been thoughtfully designed, selectively disrupts the FOXO4-p53 complex, inducing apoptosis in senescent cells while preserving healthy tissue. In aged mammalian models, administering FOXO4-DRI decreases the accumulation of senescent cells, restores cerebral blood flow and the integrity of the blood-brain barrier (BBB), reverses hippocampal atrophy, and enhances cognitive function. Furthermore, in models of Alzheimer's disease (AD) and tauopathy, this intervention eliminates amyloid-β and pathological tau, leading to improved memory performance. Preliminary human studies involving FOXO4-axis modulators, such as high-dose fisetin, show a reduction in the senescence-associated secretory phenotype (SASP) and enhancements in cognitive and physical measures among older adults. These findings collectively identify the FOXO4-p53 axis as a potential pharmacological target in brain aging and highlight senolytic therapy as a promising strategy for altering diseases to postpone or reverse age-related cognitive decline. This review consolidates recent findings indicating that FOXO4-dependent senescence significantly contributes to neuroinflammation, synaptic dysfunction, and impaired neurogenesis in the aging brain.

Effect of glucose load on metabolism in patients with type 2 diabetes during elective surgery using remifentanil-induced anesthesia:a randomized controlled trial.

J Med Invest

Asuka Kasai, Kohei Fukuta, Noriko Kambe +3 more

This study aimed to explore the effect of intraoperative glucose load on metabolism in patients with type 2 diabetes anesthetized with remifentanil. A total of 30 patients were enrolled and randomly allocated to one of two groups:no glucose or low-dose glucose (0.1 g/kg/h for 1 hour followed by 0.05 g/kg/h for 1 hour). Glucose, adrenocorticotropic hormone, 3-methylhistidine, insulin, cortisol, free fatty acid, ketone bodies, and creatinine were measured at several points before, during, and after general anesthesia. Glucose levels in the low-dose glucose group increased significantly at 1 and 2 hours after glucose infusion compared to their preanesthetic levels and to those in the no glucose group. Two patients in the low-dose glucose group had blood glucose levels exceeding 11.1 mmol/L. Free fatty acids, ketone bodies, and 3-methylhistidine/creatinine did not differ significantly between groups. Ketone body levels were significantly higher at 1 hour than preanesthetic levels in both groups;after 1 hour, however, they did not change in the no glucose group but significantly decreased in the low-dose glucose group. Intraoperative low-dose glucose load may suppress ketogenesis, but clinicians must consider the risk of causing hyperglycemia in patients with type 2 diabetes undergoing remifentanil-induced anesthesia. J. Med. Invest. 73 : 222-228, February, 2026.

Relative Adrenal Insufficiency is Associated With Worse Clinical Outcomes in Patients With Acute Decompensation of Cirrhosis and Hyponatremia.

J Clin Exp Hepatol

Tanmay Jain, Kalyani Sridharan, Rohit Gupta +4 more

Relative adrenal insufficiency (RAI) and hyponatremia are both common in decompensated cirrhosis. The literature is scarce on the prevalence and clinical correlates of RAI in patients with acute decompensation (AD) of cirrhosis and hyponatremia.

Complete glucocorticoid resistance: a lethal disorder in the neonatal period.

JCEM Case Rep

Natalie Segev, Sarah Swauger, K Nicole Weaver +3 more

Generalized glucocorticoid (GC) resistance (Chrousos syndrome) results from impaired GC receptor signaling due to variants in the NR3C1 gene. Severe neonatal presentations are extremely rare. We report an 8-week-old male infant born at 31-week gestation, with progressive respiratory failure, refractory hypotension, hypokalemic alkalosis, anasarca, jaundice, and multiorgan dysfunction. Laboratory evaluation demonstrated persistently elevated serum cortisol [>60 µg/dL (SI: >1655 nmol/L) (reference range 2.5-9.1 µg/dL, SI: 69.0-251.0 nmol/L)], adrenocorticotropic hormone [>2400 pg/mL (SI: >528 pmol/L) (reference range 7.2-63.3 pg/mL, SI: 1.6-13.9 pmol/L)], aldosterone [2036.0 ng/dL (SI: 56 nmol/L) (reference range 7.0-99.0 ng/dL, SI: 0.2-2.7 nmol/L)], and androgens despite treatment with escalating doses of dexamethasone (up to 12 mg, > 2000 mg/m2/day of hydrocortisone-equivalency). Whole-genome sequencing identified 2 NR3C1 variants: a maternally inherited variant of uncertain significance (c.2181+5 G>C) and a de novo likely pathogenic ∼7.9 kb deletion encompassing exon 8. In silico analyses suggested both variants could disrupt the GC receptor ligand-binding domain, potentially resulting in complete loss of GC receptor function. Autopsy demonstrated adrenomegaly with marked proliferation of zona fasciculata, cholestasis with bile duct paucity, and chronic neonatal lung disease. This case represents a rare and fatal manifestation of complete generalized GC resistance. It highlights the broad physiological role of GC in neonatal homeostasis.

Carnosine Augments the Efficacy of Pulmonary Rehabilitation in COPD: Insights from a Preclinical Model.

Clin Sci (Lond)

Ross Vlahos, Suleman Abdullah Almerdasi, Stanley M H Chan +8 more

Pulmonary rehabilitation (PR) improves exercise tolerance and dyspnoea in chronic obstructive pulmonary disease (COPD) but does not address the elevated cardiovascular disease (CVD) risk. Vascular dysfunction, an early CVD feature, is driven by oxidative stress-a shared pathogenic mechanism in COPD and CVD. Carnosine, a bioactive dipeptide with antioxidant and pH-buffering properties, may enhance muscle performance and protect against vascular injury. This study sought to determine whether carnosine supplementation combined with exercise training could modify early CVD features in a preclinical COPD model. Male BALB/c mice were exposed to room air or cigarette smoke (CS; 9 cigarettes/day, 5 days/week, 8 weeks) with or without carnosine (1 mg/mL in drinking water) and with or without treadmill exercise training (50% maximal speed; 30 min/day, 5 days/week). After 8 weeks, blood pressure, exercise capacity, resting heart rate, lung inflammation, systemic oxidative stress, aortic endothelial function, and platelet activation were assessed. CS impaired weight gain, reduced exercise capacity, elevated resting heart rate, and induced airway inflammation (p<0.0001). CS also caused severe endothelial dysfunction and platelet activation (p<0.0001). Exercise alone did not reverse these vascular abnormalities. In contrast, carnosine plus exercise restored weight gain, exercise capacity, and heart rate, preserved endothelial function, and prevented platelet adhesion and activation, without altering airway inflammation. Exercise training alone is insufficient to counteract CS-induced vascular injury. Carnosine supplementation provides synergistic vascular protection, highlighting its potential as an adjunct to PR to mitigate oxidative stress-driven CVD risk in COPD.

Effect of Once-Daily Macitentan 75 mg on the Pharmacokinetics of Sildenafil, Riociguat, or Rosuvastatin in Healthy Male Participants.

J Clin Pharmacol

Dénes Csonka, Cynthia Gargano, Navin Goyal +3 more

Macitentan is an oral, dual ETA/ETB endothelin receptor antagonist, currently approved in adults for the treatment of pulmonary arterial hypertension (PAH) at a once-daily dose of 10 mg. Pre-clinical and clinical data suggest that greater ETB receptor inhibition may result in greater efficacy. This hypothesis is being tested in the Phase 3 UNISUS study (NCT04273945), comparing once-daily macitentan 75 mg versus macitentan 10 mg. The present Phase 1 study (NCT04211272) evaluated the pharmacokinetics and safety of concomitant administration of once-daily macitentan 75 mg at steady state with substrates of either breast cancer resistance protein (BCRP) transporter (e.g., riociguat and rosuvastatin) or cytochrome P450 3A4 (CYP3A4) enzymes (e.g., sildenafil and tadalafil) in healthy male adults. Macitentan was administered once daily at 10 mg on Days 1 and 2, 37.5 mg on Days 3-5, and 75 mg on Days 6-13. Participants received a single oral dose of sildenafil (20 mg) on Days -4 and 13, riociguat (1 mg) on Days -3 and 10, or rosuvastatin (10 mg) on Days -4 and 10. Geometric mean ratios for the maximum concentration and area under the curve of the substrate and 90% confidence intervals showed no clinically relevant effects on exposure for sildenafil, riociguat, or rosuvastatin when administered alone or with macitentan 75 mg. Co-administration of macitentan and the substrates was generally well tolerated. Due to the lack of clinically relevant drug-drug pharmacokinetic interactions, no dose adjustment is deemed necessary when co-administering once-daily macitentan 75 mg with BCRP or CYP3A4 substrates.

Peptidomimetic Long-Acting Growth Hormone-Releasing Hormone Agonists Promote Tissue Perfusion in Hindlimb Ischemia.

J Med Chem

Haodong Shao, Yuling Wu, Mengyu Mao +9 more

Growth hormone-releasing hormone (GHRH) has shown therapeutic potential in the treatment of various diseases. However, the clinical translation of GHRH receptor (GHRH-R) agonists has been hampered by the short half-life and suboptimal activity. Herein, we report a series of hybrid GHRH analogs developed using sulfono-γ-AA peptide-based peptidomimetic optimization. These hybrid peptides exhibit significantly enhanced potency in activating GHRH-R and stimulating growth hormone release while demonstrating markedly improved serum stability (T1/2 > 24 h). Subcutaneous administration of selected peptides in mice with ischemic hindlimb enhanced blood perfusion and preservation of limb function. They also promoted endothelial regeneration and collateral vessel formation, enhancing vascular remodeling and tissue repair. In vitro, the peptides enhanced the angiogenic potential of endothelial cells, primarily through activation of the ERK signaling pathway. Our findings lay a strong foundation for the development of long-acting GHRH-R agonists with promising therapeutic potential for the treatment of vascular and regenerative disease.

Is There a Causal Link Between GLP-1 Receptor Agonists and Non-Arteritic Anterior Ischaemic Optic Neuropathy? A Critique of the Clinical Evidence.

Clin Exp Ophthalmol

Helen V Danesh-Meyer, Joseph F Rizzo

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for managing Type 2 diabetes and obesity, with well-documented and significant cardiometabolic benefits. Recent observational reports and pharmacovigilance data have raised concerns about a possible association between GLP-1RAs-particularly semaglutide- and non-arteritic anterior ischaemic optic neuropathy (NAION), a rare cause of sudden vision loss. While case reports and spontaneous reporting systems suggest a potential signal, these sources are subject to confounding and reporting bias. Observational studies offer mixed findings, with some Scandinavian registry studies reporting elevated risks while large electronic health record EHR) analyses from the U.S. and multi-national databases have reported null or weak associations. Meta-analyses of randomised controlled trials- the gold standard for causal inference- currently lack power to reliably assess this rare outcome but suggest, at most, a comparatively moderate increase in risk (e.g., odds ratio of 2-3). Overall while a causal link cannot be excluded, the numerous studies that assert an 'association' between GLP-1 RA exposure and NAION should motivate larger pooled analyses of RCTs with adjudicated ocular outcome to definitely assess risk.

LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial.

BMJ Open

Ameenah A Alawadhi, Dherar Alroudhan, Dalal J Alsaeed +6 more

Obesity is a global public health issue, with its effects a particular issue in Kuwait. Advances in pharmaceutical treatment (eg, glucagon-like peptide-1s) offer an effective solution, with the magnitude of weight lost something to celebrate. However, this level of weight loss also results in dramatic reductions in lean mass, reflecting loss of muscle mass and muscle strength which can predispose people to sarcopenia. This is a particular issue in people with type 2 diabetes in Kuwait, where the prevalence of muscle weakness is extremely high. Solutions to mitigate this loss of muscle mass and strength are needed, with a pragmatic resistance exercise intervention and increasing dietary protein intake having potential. This trial aims to determine whether resistance exercise and/or protein intake can preserve muscle mass and improve physical function in people with obesity initiating semaglutide/tirzepatide therapy.

Combined antiretroviral therapy with low- or normal-protein, high-calorie diets appears to induce significant deleterious electrocardiographic changes in a rodent model.

Braz J Med Biol Res

B M Chege, P W Mwangi, C G Githinji +1 more

The introduction of combination antiretroviral therapy (cART) has significantly reduced AIDS-related morbidity and mortality. However, the prevalence of age-associated comorbidities, particularly cardiovascular diseases (CVD), has increased, becoming a leading cause of mortality in people living with HIV. This study investigated the interaction between cART regimens and dietary composition on electrocardiographic (ECG) parameters and myocardial histopathology. A total of 120 weanling Sprague Dawley rats were allocated to one of three diets for 15 weeks: normal chow, a calorie-dense low protein (CDLP) diet, or a calorie-dense normal protein (CDNP) diet. Each dietary group was then subdivided into four treatment groups for a further 9 weeks: a standard group (normal saline), Test group 1 (dolutegravir (DTG) plus tesamorelin), Test group 2 (DTG only), and a positive control (classical cART regimen). ECG recordings and histological assessments were performed at week 24. Significant intergroup variations in ECG indices were observed, including Q, R, S, and T wave amplitudes, PR interval, QRS duration, ST height, and QTc (all P<0.0001). Myocardial fibrosis (P<0.0001) was evident in animals from the TG2 (DTG only) and PC (classical regimen) groups maintained on CDLP and CDNP diets. These findings demonstrated that CDLP and CDNP diets, combined with DTG-based or classical cART regimens, exerted deleterious cardiac effects, promoting myocardial fibrosis that disrupts normal electrical conduction and may predispose to arrhythmogenesis. Tesamorelin prevented these effects, implicating growth hormone pathway dysfunction in the underlying pathology.

Semaglutide-Associated Acute Pancreatitis in a Patient With Type 2 Diabetes Mellitus: A Case Report.

Cureus

Piyush Puri, Michael Akhavan, Jonathan Shadan +2 more

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist widely prescribed for type 2 diabetes mellitus and obesity, is generally well tolerated but can be associated with gastrointestinal adverse effects and, rarely, pancreatitis. As its use grows, clinicians must remain aware of potential complications, particularly in patients with additional risk factors. We report the case of a 57-year-old woman with diabetes, hypertension, and hyperlipidemia who presented with acute severe epigastric pain and persistent vomiting shortly after consuming a large, fatty meal. She had been receiving semaglutide for several months. Laboratory studies showed marked leukocytosis, hyperglycemia with an anion gap metabolic acidosis, and a lipase level exceeding 3000 U/L. CT imaging demonstrated acute interstitial edematous pancreatitis with peripancreatic fluid and early concern for necrosis. She was treated conservatively with aggressive intravenous hydration, bowel rest, electrolyte repletion, and analgesia. Her condition improved with supportive care, and she was discharged with close outpatient follow-up. This case highlights the importance of recognizing pancreatitis as a possible multifactorial complication in patients using GLP-1 receptor agonists. This case highlights the need for clinicians to maintain awareness of pancreatitis as a potential adverse effect in patients receiving semaglutide, especially those with additional risk factors such as biliary pathology or dietary triggers. As the use of GLP-1 receptor agonists continues to grow, careful assessment of abdominal symptoms and early recognition of pancreatic inflammation are essential for optimizing outcomes and guiding safe prescribing practices.