Search Results (290)

Both diabetes mellitus (DM) and stroke are major global health challenges with high morbidity and mortality. DM is a major risk factor for stroke, contributing to both increased incidence and worse clinical outcomes. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), as well as dual agonists like tirzepatide, have demonstrated significant cardiovascular benefits, raising interest in their potential cerebrovascular effects. This narrative review examines the pathophysiological links between DM and stroke and summarizes recent clinical evidence on the efficacy of GLP-1 RAs and dual GLP-1/GIP receptor agonists (GLP-1/GIP RAs) in stroke prevention and management. Current evidence from large cardiovascular outcome trials supports the role of GLP-1 RAs in reducing major adverse cardiovascular events, including stroke, primarily in the context of primary and secondary prevention. Findings suggest that semaglutide and liraglutide may reduce non-fatal stroke incidence, decrease hospitalizations, and improve neurological outcomes in patients with prior stroke. Comparative analyses of major trials suggest that, although stroke reduction may be a class effect of GLP-1 RAs, meaningful differences exist between individual agents, likely due to variations in pharmacokinetics, receptor affinity, and study populations. Additionally, much of the evidence in acute stroke derives from early-phase or ongoing trials, warranting cautious interpretation. Novel therapies, including orforglipron and retatrutide, as well as combinations like Maridebart cafraglutide and CagriSema, may expand future therapeutic options for individuals at high cerebrovascular risk. GLP-1-based therapies show promising neurovascular effects, but large-scale, long-term studies are needed to define their role in post-stroke management and cerebrovascular risk reduction. Overall, GLP-1 RAs should currently be regarded primarily as agents for long-term vascular risk reduction rather than established therapies for acute stroke. While potential neuroprotective effects are emerging, these require confirmation in adequately powered randomized trials. Future studies should aim to identify the patient subgroups most likely to benefit and to determine whether specific agents confer advantages in acute cerebrovascular contexts. A better understanding of the mechanisms underlying potential neuroprotection will be essential to determine whether these therapies can be effectively integrated into stroke management strategies. Full article

Alcohol use disorder (AUD) remains a crucial public health challenge worldwide. The currently available medications for AUD remain limited in the number and efficacy, meaning that the development of new treatments is of critical importance. Agonists of glucagon–like peptide–1 receptor (GLP–1RAs) have recently received attention as a potential anti–addiction treatment, particularly in AUD. This review presents data from preclinical studies in rodents and non–human primates, registered clinical trials, observational studies, and social media posts, investigating the effects of GLP–1RAs on alcohol–related behaviors and consumption. Several GLP1–RAs and tirzepatide (a dual agonist of GLP–1R and glucose–dependent insulinotropic polypeptide receptor; GIP–R) reduced alcohol consumption and alcohol–seeking behaviors, alcohol–induced locomotor stimulation and memory of alcohol reward, and suppressed relapse drinking in rodents. In addition, they prevent acute alcohol from activating the mesolimbic dopamine system. There are limited human data on the role of the GLP–1 system in AUD. In registered clinical trials, exenatide, semaglutide, and dulaglutide reduced alcohol consumption. Pharmacoepidemiologic studies documented a decreased risk of alcohol–related events in AUD patients using various GLP–1RAs and tirzepatide. Together, existing preclinical and clinical data suggest that GLP–1 is involved in the AUD process and imply the role of GLP1–RAs as a tentative treatment for AUD. Full article

Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has transformed obesity and diabetes management. However, its expanding use among reproductive-age women raises concerns about potential effects on early placental development. We examined semaglutide’s impact on two human trophoblast cell lines: Swan71 (invasive extravillous) and BeWO (syncytiotrophoblast-like). Cells were treated with semaglutide (100 nM) for 24 h, and proliferation, viability, mitochondrial respiration, oxidative stress, signaling pathways, and invasiveness were evaluated. Semaglutide significantly reduced proliferation in Swan71 cells and increased it in BeWO cells, with no significant change in viability for Swan71 and a slight increase for BeWO. Western blot analysis revealed altered phosphorylation of key signaling proteins, including mTOR, p70S6K, 4EBP1, AKT, and ERK, as well as increased AMPK phosphorylation, indicating a shift toward catabolic signaling. Reactive oxygen species (ROS) accumulation increased markedly, accompanied by altered oxygen consumption rates—reduced in Swan71 cells and elevated in BeWO cells. Functionally, semaglutide suppressed Swan71 invasion through Matrigel by approximately three-fold. These findings suggest that semaglutide induces oxidative and metabolic stress in trophoblasts and is associated with altered mTOR-mediated signaling and reduced invasive potential. Such cellular alterations may contribute to compromised placental development and uterine vascular remodeling if exposure occurs near conception. While clinical data remain limited, this study provides mechanistic insight supporting caution in the use of semaglutide during the periconception period and underscores the need for targeted reproductive safety studies. Full article

Obesity contributes to an increase in the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and is diagnosed when hepatic steatosis is accompanied by at least one of the following factors: obesity or overweight, diabetes mellitus, or signs of metabolic abnormalities. MAFLD is a term that encompasses a wide range of liver disorders, ranging from simple steatosis to metabolic steatohepatitis, which can progress to cirrhosis and eventually, hepatocellular carcinoma (HCC). Lipotoxicity generated by a high-fat diet causes liver inflammation, therefore, blocking inflammatory pathways is considered a promising strategy to prevent MAFLD progression. Inflammatory responses and oxidative stress are linked to endoplasmic reticulum stress, thereby activating the unfolded protein response (UPR) pathway. Although drugs such as resmetirom and semaglutide have recently been approved for the treatment of MAFLD, there is still a need to identify complementary therapies with different mechanisms of action. In this context, the present study evaluated the hepatoprotective effect of ellagic acid through the modulation of mRNAs of proteins in the UPR-Perk pathway in a murine model fed a high-calorie diet. This study revealed that the high-calorie diet activated the UPR pathway in response to stress, increasing the expression of the Grp78, Eif2ak3, Eif2α, Ddit3, Atf4, and Nfe2l2 genes in the liver and epididymal adipose tissue. Ellagic acid modulated the pathway genes and reduced levels of glucose, total cholesterol, HDL and VLDL, triglycerides, insulin, and glycated hemoglobin, and could therefore be considered a hepatoprotective agent. Full article

Background/Objectives: Lean metabolic dysfunction-associated steatotic liver disease (lean MASLD) is an increasingly recognized phenotype occurring in individuals with normal body mass index (BMI), despite clinically important hepatic and cardiometabolic risk. This narrative review summarizes current evidence on its epidemiology, pathophysiology, diagnostic challenges, clinical outcomes, and management. Methods: A narrative literature review was conducted using PubMed, Embase, and Cochrane Library from database inception to March 2026. Relevant studies on lean MASLD/lean NAFLD, including cohort studies, meta-analyses, clinical trials, consensus statements, and practice guidelines, were prioritized. Results: Lean MASLD reflects interactions between visceral adiposity, insulin resistance, genetic susceptibility, sarcopenia, dietary and lifestyle factors, vitamin D deficiency, and gut microbiome alterations. Diagnosis is challenging because BMI and aminotransferase levels may underestimate metabolic vulnerability, MASH, or clinically significant fibrosis. Available data suggest increased liver-related events, liver-related mortality, and all-cause mortality compared with individuals without steatotic liver disease, although comparisons with non-lean MASLD remain heterogeneous. Resmetirom and semaglutide have expanded treatment options for noncirrhotic MASH with moderate to advanced fibrosis, but lean patients are underrepresented in pivotal trials. Conclusions: Lean MASLD is an underrecognized but clinically important phenotype. Earlier recognition, fibrosis risk stratification, sarcopenia assessment, cardiometabolic optimization, and lean-specific therapeutic research are needed to improve outcomes. Full article

Background/Objectives: Poly(lactic-co-glycolic acid) (PLGA) microspheres are widely used in long-acting injectable (LAI) formulations because PLGA exhibits well-established biocompatibility and undergoes controlled hydrolytic degradation into metabolizable byproducts. However, optimization of microspheres typically requires time-consuming in vitro testing. Therefore, we developed a predictive machine learning model for early-stage and full time-dependent release profiles of drug-loaded PLGA microspheres. Methods: Using a published dataset comprising 321 release profiles from 89 drugs, we first developed a classification model to identify slow-release behavior (≤20% release within 3 days) and subsequently integrated the predicted early-release probability into a regression model to estimate cumulative release over time. Results: Among tree-based ensemble models, XGBoost achieved the lowest mean absolute error (MAE = 0.126) and highest Pearson correlation coefficient (r = 0.831). SHapley Additive exPlanations (SHAP) analysis revealed that drug and polymer molecular weight, predictive slow-release probability, and polymer concentration substantially influence release behavior. We also assessed this framework with external datasets. Drug release data for olaparib-loaded PLGA microspheres were obtained in-house, whereas those for semaglutide-based microspheres were obtained from the published literature. In both datasets, this framework demonstrated low MAE values (0.096 and 0.068, respectively). Conclusions: This suggests that the proposed framework can predict in vitro drug release and support efficient optimization of PLGA-based LAI formulations. Full article

Background: Glucagon-like peptide-1 (GLP-1)-based therapies offer significant cardiometabolic benefits. Obesity-related heart failure with preserved ejection fraction (HFpEF) arises from a complex interplay of increased lipids, chronic inflammation, and metabolic disturbances. These factors not only exacerbate the disease but also affect GLP-1 pathways, supporting the potential role of GLP-1-based therapies in targeting this condition. Objective: This review aimed to synthesize the current evidence on GLP-1-based therapy in HFpEF, focusing on mechanisms of action, clinical outcomes, and practical significance. Methodology: A narrative review using PubMed and Scopus was conducted, including studies published between January 2020 and March 2026. Evidence from randomized trials, pooled analyses, mechanistic studies, and observational data was incorporated. Results: GLP-1-based therapies, including semaglutide and tirzepatide, demonstrated significant improvements in symptoms, exercise capacity, and quality of life. These benefits are closely linked to weight loss, reduced inflammation, and improved congestion indices. Tirzepatide use has also been associated with a reduction in heart failure-related complications. The underlying mechanisms likely involve coordinated effects on metabolism, inflammation, hemodynamics, and cardiac remodeling. Current evidence suggests that its efficacy in improving morbidity rates is stronger than its efficacy in reducing mortality rates. Conclusions: GLP-1-based therapies offer a promising, phenotypically targeted approach to managing obesity-associated HFpEF. However, their long-term effects on mortality remain unclear, highlighting the need for further research. Further studies should refine patient selection and define optimal clinical integration. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and newer dual-incretin therapies have become central to the treatment of diabetes mellitus and obesity, with benefits extending beyond glycemic control. Their expanding use has prompted growing interest in their potential ocular effects. Experimental data support plausible protective mechanisms, including reduction in oxidative stress and neuroprotective effects on retinal and optic nerve tissues. Clinical evidence, however, remains heterogeneous. In diabetic retinopathy, the main concern appears to be transient early worsening associated with rapid glycemic improvement rather than direct retinal toxicity. A potential semaglutide-associated signal for non-arteritic anterior ischemic optic neuropathy has raised concern, although the absolute risk appears low and causality remains unproven. Emerging studies also suggest possible beneficial associations with glaucoma, ocular surface diseases, and certain retinal vascular outcomes, whereas the evidence regarding age-related macular degeneration and cataract remains conflicting or preliminary. Overall, ocular outcomes associated with incretin-based therapies seem to reflect a complex interplay among drug-specific pharmacology, systemic metabolic changes, and individual patient susceptibility rather than a class effect. Baseline ophthalmic assessment and individualized follow-up may be advisable in selected high-risk patients. Further prospective ophthalmology-focused studies are needed to clarify long-term safety and identify the patients most likely to benefit or develop adverse events. Full article

Introduction: Self-medication has become a growing concern, especially in the current era of digitalization. The ubiquitous access to social media platforms has been associated with this behaviour due to factors like body image leading to weight loss obsession and seeking solutions to achieve the ideal body image and weight. Aims: This research also examined the relationship between Social Media Usage and Self-Medication, Weight Loss Obsession, and further Intention to Use Ozempic (semaglutide) among university students in the United Arab Emirates. Methods: The researchers used a cross-sectional design and gathered data from students enrolled at Al Ain University, United Arab Emirates. Data were analyzed using SPSS (Version 29) and SmartPLS software (Version 4). Descriptive statistics and Partial Least Squares Structural Equation Modelling (PLS-SEM) were employed to examine relationships among variables based on the Self-Medication Theory by Khantzian. Results: It was found that Social Media Usage was significantly linked with Self-Medication behaviour among the students. Also, this usage makes individuals conscious about weight and body image as important concerns. Finally, Social Media Usage was also significantly linked with Intention to Use Ozempic for weight loss without medical prescriptions and doctor consultations. Conclusions: It is concluded that self-medication for weight loss disregards the significance of maintaining a well-balanced diet and regular exercise, leading to serious health risks, i.e., nutritional deficiencies, metabolic disorders, and negative effects on mental well-being. Educating and informing young individuals about the importance of adopting healthy and sustainable weight loss processes is important, underlining the need for professional guidance, nutrition education, and promoting a positive body image. This approach may help reduce the harmful outcomes associated with self-medication for weight loss. Full article

Background: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use has increased exponentially as studies show significant benefits in cardiovascular and renal diseases and obesity. Accessibility to the public also increased after compounding pharmacies began direct-to-consumer distribution. Gastrointestinal side effects are common; however, hypersensitivity reactions are rare. Case Presentation: A 50-year-old female with a history of obesity, hypertension, and lisinopril-induced angioedema presented to the Emergency Department with swelling of the lips, tongue, and throat developing four hours after her first injection of compounded semaglutide for weight loss. She was treated with epinephrine, corticosteroids, and antihistamines, but due to progressive airway edema, she required intubation and mechanical ventilation for four days. After extubation, she reported accidentally injecting a ten-fold higher dose (2 mg) of semaglutide than was appropriate for the first dose. The hospitalization was complicated by hypoglycemia requiring dextrose infusion, but was otherwise unremarkable, and she was discharged home on day 7. Based on the temporal onset after semaglutide injection, this presentation was most consistent with GLP-1 RA-induced angioedema. While she also had a history of lisinopril-induced angioedema five years earlier, and had been taking valsartan for hypertension, the remoteness of the lisinopril exposure made this less likely. Conclusions: Semaglutide use may be associated with severe angioedema within hours of administration. Given the overlapping indications and patient populations, angioedema appearing in patients taking both GLP-1 RAs and ACE inhibitors may become increasingly common and present a diagnostic dilemma. Diagnosis of hypersensitivity to GLP-1 RAs can be supported with history and positive skin testing. Clinicians should be aware that inexperienced patients are at the highest risk of dosing errors. Full article

The obesity–metabolic syndrome–diabetes continuum is driven by interconnected mechanisms including insulin resistance, dysfunctional adiposity, chronic inflammation and progressive cardio–renal–metabolic injury. This triggered a need for therapies that extend beyond glucose lowering alone. The benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as disease-modifying drugs include weight loss, cardiovascular risk reduction, glycemic control and renal protection. However, treatment burden, adherence issues and access restrictions may limit the long-term effects of injectable formulations. One significant translational development that aims to close this gap is oral GLP-1-based treatments. In this review, we examine the mechanistic rationale, formulation science and clinical development of oral GLP-1 RAs. Oral semaglutide is presented as the first validated proof of concept for systemic peptide delivery by the gastrointestinal route. The biological barriers to oral peptide absorption, including enzymatic degradation, low epithelial permeability, pharmacokinetic variability and epithelial safety constraints, are critically discussed. Enabling technologies such as SNAC-based gastric absorption, nanocarriers, mucoadhesive systems and stability-optimization platforms are evaluated. Evidence from the PIONEER program and related studies demonstrating meaningful glycemic and weight-loss efficacy, acceptable safety and clinical utility in patients with type 2 diabetes and chronic kidney disease is further synthesized. Beyond first-generation oral peptide platforms, we discuss the emerging landscape of non-peptide oral GLP-1 RAs, dual and triple incretin agonists, precision dosing strategies and model-informed drug development. Oral GLP-1-based therapeutics are shifting from a formulation breakthrough to a broader translational strategy for disease modification across the obesity–metabolic syndrome–diabetes continuum. Long-term renal outcomes, access and implementation barriers remain important priorities for future research. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have revolutionized the management of type 2 diabetes mellitus (T2DM) by providing robust glycemic control alongside significant cardioprotective and renoprotective benefits. This review synthesizes current mechanistic, preclinical, and clinical evidence regarding the impact of GLP-1RAs on retinal microvasculature and summarizes the current clinical evidence of GLP-1RA-induced retinal complications. GLP-1RAs exert pleiotropic effects on the retinal microvasculature, offering protection by amelioration of endothelial function, reduction in oxidative stress, inflammation, microvascular remodeling, and preservation of the blood–retinal barrier (BRB). Despite these mechanistic advantages, emerging clinical data have raised concerns regarding potential retinal adverse events associated with GLP-1RA therapy. Observational studies and pharmacovigilance analyses have suggested possible associations with non-arteritic anterior ischemic optic neuropathy (NAION), diabetic macular edema (DME), vitreous hemorrhage, retinal detachment, macular hole formation, and progression of diabetic retinopathy (DR), particularly in the context of semaglutide use. Most evidence comes from retrospective studies or secondary endpoints, limiting causal inference. Retinal complications associated with GLP-1RAs remain heterogeneous and inconclusive, requiring careful evaluation of potential risks across diverse patient populations. Future research should conduct large, randomized trials with standardized ocular endpoints, detailed imaging, and stratified analyses to clarify GLP-1RA retinal safety. Full article

The recent redefinition of steatotic liver diseases, introducing metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), reflects a growing consensus among liver societies and marks a paradigm shift in disease classification. MASLD subsumes former categories of nonalcoholic fatty liver disease (NAFLD) and incorporates metabolic criteria alongside moderate alcohol intake, while MASH replaces nonalcoholic steatohepatitis (NASH), aligning terminology with disease mechanisms. This evolution clarifies the diagnostic criteria and minimizes stigma, facilitating more consistent epidemiological and clinical investigations. Recent advances in noninvasive diagnostics, including vibration-controlled transient elastography, magnetic resonance elastography, shear-wave elastography, and the Enhanced Liver Fibrosis test, have improved the identification and stratification of patients with advanced fibrosis. Current guidelines recommend targeted screening in populations at elevated metabolic risk, enabling earlier intervention and personalized management. Population studies indicate that MASLD affects over one-third of adults and is a major contributor to cardiovascular and metabolic morbidity. Therapeutic progress is highlighted by the approval of novel agents such as resmetirom and semaglutide for the treatment of MASH with fibrosis. Emerging dual and triple agonists, as well as sodium–glucose cotransporter inhibitors, offer additional promise, although further research is required to define their long-term efficacy and safety. As the disease prevalence escalates globally, the integration of multidisciplinary care, the ongoing refinement of diagnostic tools, and the expansion of therapeutic options will remain essential to optimizing outcomes for affected individuals. Full article

Adverse Drug Reactions (ADRs) represent a major public health concern due to their impact on patient safety. In Spain, the Spanish Agency of Medicines and Medical Devices, through the FEDRA database, coordinates the reporting of suspected ADRs under real-world conditions of use, contributing to the continuous updating of safety information. In this context, community pharmacist, through Professional Pharmaceutical Care Services, plays a key role in the early detection of ADRs and Drug-Related Problems (DRPs). This article describes the case of a 70-year-old polymedicated woman included in a Personalized Dosage System (PDS). Following the substitution of diazepam with clonazepam and an increase in the dose of semaglutide, the patient developed urinary incontinence, nausea and abdominal pain. Coordinated intervention between the community pharmacy and primary care enabled adjustment of the clonazepam dose, optimization of semaglutide administration and discontinuation of unnecessary naproxen use. These measures resulted in improved treatment tolerance and safety, as well as optimization of pharmacotherapy. Full article

Background: Obesity is a heterogeneous chronic disease in which eating behavior phenotypes may influence treatment response. Yet, anti-obesity medication (AOM) selection is still largely guided by anthropometric and metabolic parameters, with limited use of behavioral phenotyping in routine practice. We evaluated whether multidimensional eating behavior changes, measured by the Brazilian Eating Behavior Phenotype Scale (Escala de Fenótipos do Comportamento Alimentar, EFCA), differ across commonly used AOMs in a real-world cohort. Methods: We conducted a retrospective, observational, real-world study in obesity outpatient care settings in São Paulo, Brazil. Adults with obesity (18–65 years) treated with a single principal AOM for 6 months and paired baseline/6-month follow-up EFCA and anthropometric data were included. Analyses focused on early responders (≥5% total body weight loss at 3 months). Five AOM groups available in Brazil were analyzed: semaglutide (oral or subcutaneous), naltrexone/bupropion, sibutramine, topiramate, and tirzepatide. Outcomes included percent weight loss, EFCA total score, and five EFCA subscales (hedonic, emotional, compulsive, hyperphagic, disorganized). Within-medication behavioral changes were assessed using paired tests and standardized effect sizes (Cohen’s dz, 95% CI), summarized in heatmap form. Results: The analytical cohort comprised 66 early responders with paired EFCA assessments at baseline and 6 months. EFCA profiling revealed distinct behavioral response fingerprints across AOMs. Effect size mapping showed predominantly large behavioral effects (many dz ≥ 0.8) in hedonic, emotional, hyperphagic, and compulsive domains. Strongest signals included emotional eating reductions with naltrexone/bupropion (dz 2.04), tirzepatide (dz 1.77), semaglutide (dz 1.52), and topiramate (dz 1.54); hedonic reductions with tirzepatide (dz 2.06), semaglutide (dz 1.55), and naltrexone/bupropion (dz 1.52); hyperphagic reductions with tirzepatide (dz 1.50) and semaglutide (dz 1.34); and compulsive reductions with topiramate (dz 1.41) and consistent effects across tirzepatide, semaglutide, and sibutramine (≈dz 0.95–0.96). Disorganized eating showed heterogeneous/attenuated responsiveness, from near-null with tirzepatide (dz 0.03) to large but imprecise effects in smaller groups (e.g., topiramate dz 1.24, wide CI). Conclusions: In this responder-enriched real-world cohort, AOMs showed distinct and reproducible EFCA behavioral signatures, supporting a clinically actionable phenotype-informed framework to prioritize, sequence, and monitor obesity pharmacotherapy beyond nonspecific weight reduction, while highlighting disorganization as a potential target for adjunctive behavioral strategies. Full article