Search Results (300)

Sarcopenia is a prevalent and disabling complication of chronic kidney disease (CKD), associated with frailty, diminished quality of life, and increased morbidity and mortality. Despite its clinical significance, no pharmacological treatments are currently approved to address muscle wasting in this population. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in the management of type 2 diabetes and obesity, have shown potential to support muscle mass and function through pleiotropic mechanisms. These include anti-inflammatory and antioxidant actions, improvements in insulin sensitivity and energy metabolism, and mitochondrial support. Given the high burden of sarcopenia in CKD and the frequent overlap with metabolic and cardiovascular comorbidities, GLP-1RAs may offer a novel therapeutic approach. This review examines the biological plausibility and emerging evidence supporting the role of GLP-1RAs in preserving muscle health in CKD, highlighting the need for targeted clinical trials and mechanistic investigations to establish their efficacy in this high-risk group. Full article

Background/Objectives: The growing prevalence of metabolic-associated steatotic liver disease (MASLD)/metabolic-associated steatohepatitis (MASH) is forecasted to be over 55% by 2040, representing a significant driver of cirrhosis and highlighting demand for effective therapeutic interventions. The therapeutic landscape is evolving with agents, like glucagon-like peptide-1 receptor agonists (GLP-1 RAs), under active investigation. A common concern across emerging therapies is potentially precipitating decompensation in patients with existing cirrhosis, necessitating careful consideration in this population. Case Presentation: A 46 y.o. female with obesity and cirrhosis from MASH and alcohol who underwent a deceased-donor liver transplant developed steatohepatitis within a year post-transplant after gaining 36 kg. Transient elastography revealed controlled attenuation parameter (CAP) 400 dB/m (S3 steatosis) and liver stiffness measurement (LSM) 61.2 kPa (advanced fibrosis). Follow-up biopsy confirmed severe steatohepatitis (NAS 7/8) and advanced fibrosis (F3), attributed to metabolic dysfunction without evidence of alcohol recurrence. She decompensated with ascites and varices, leading to transplant re-enlistment at MELD-Na 29. Despite two years of intensive lifestyle modification, losing 17 kg, and recompensation, her follow-up elastography showed persistent steatosis (S3) and advanced fibrosis (F4). Subsequent allograft biopsy revealed progression to cirrhosis (F4) with ongoing steatohepatitis (NAS 3/8). Tirzepatide was initiated for the development of type 2 diabetes, attributed to steroids used for immunosuppression. After 2 years on tirzepatide, she lost 43.1 kg. Shockingly, her follow-up elastography demonstrated fibrosis regression with LSM 5.5 kPa (F1) and steatohepatitis resolution with CAP 204 dB/m (S0). Follow-up liver biopsy confirmed fibrosis regression to F2-F3 and steatohepatitis resolution (NAS 1/8). Conclusions: This case challenges the widely accepted dogma that liver MASH cirrhosis is irreversible. Using multiple liver fibrosis monitoring modalities, cirrhosis reversal was demonstrated and attributed to mechanisms of GLP-1/GIP RA therapy. This study suggests that GLP-1/GIP RA may be safe in cirrhosis and may result in fibrosis regression. Full article

Aims: Individual weight loss results achieved with Glucagon-like Peptide-1 receptor agonists (GLP-1RA) vary significantly. Our aim was to describe the characteristics of patients with obesity who achieved ≥ 20% total weight loss (TWL) on liraglutide and appraise those findings through the prism of an evolving spectrum of GLP-1RA. Methods: This longitudinal prospective cohort study included 21 patients (90.5% females, age 50 (IQR 17) years, class II/III obesity (Body Mass Index ≥ 35 kg/m²) followed at the Edmonton Adult Bariatric Clinic for 65.1 (IQR 15.5) weeks. All patients received treatment with liraglutide 3.0 mg subcutaneously daily along with involvement in an integrated lifestyle modification program. Results: Liraglutide was well-tolerated, with its benefits experienced by >90% of patients. The vast majority were consistently tracking calories (95.2%, n = 20) and protein intake (90.5%, n = 19), achieving a calorie deficit of 651 (IQR 323) kcal/day, and had their mental health conditions and psychological issues successfully managed. At 16, 26, and 52 weeks, TWL was 14.3% (IQR 3.7), 18.7% (IQR 8.8), and 25.9% (IQR 9.6), respectively (p < 0.001). Over 20% TWL was achieved by 72.2% of patients by week 52. Conclusions: A select number of patients with obesity will attain weight loss that rivals bariatric surgery using liraglutide monotherapy. Despite liraglutide being less effective compared to newer agents on the market, some individuals will respond strongly and should be considered when other therapies are inaccessible. Given the societal burden and numerous challenges faced by people with obesity, GLP-1RA should be pursued in clinical practice to assist in achieving weight loss goals while being convenient and safe. Full article

Substance use disorders (SUDs) remain a major public health challenge, with existing pharmacotherapies offering limited long-term efficacy. Traditional treatments focus on dopaminergic systems but often overlook the complex interplay between metabolic signals, neuroplasticity, and conditioned behaviors that perpetuate addiction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes and obesity, have recently emerged as promising modulators of reward-related brain circuits. This review synthesizes current evidence on the role of glucagon-like peptide-1 (GLP-1) and its receptor in modulating craving and substance-seeking behaviors. We highlight how GLP-1 receptors are expressed in addiction-relevant brain regions, including the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC), where their activation influences dopaminergic, glutamatergic, and GABAergic neurotransmission. In addition, we explore how GLP-1 signaling affects reward processing through gut–brain vagal pathways, hormonal crosstalk, and neuroinflammatory mechanisms. Preclinical studies demonstrate that GLP-1RAs attenuate intake and relapse-like behavior across a range of substances, including alcohol, nicotine, and cocaine. Early-phase clinical trials support their safety and suggest potential efficacy in reducing craving. By integrating findings from molecular signaling, neurocircuitry, and behavioral models, this review provides a translational perspective on GLP-1RAs as an emerging treatment strategy in addiction medicine. We propose that targeting gut–brain metabolic signaling could provide a novel framework for understanding and treating SUDs. Full article

Glucagon-like peptide 1 (GLP-1), a hormone derived from the proglucagon gene, regulates various physiological processes; however, its impact on pregnancy outcomes remains poorly understood. Assessing the effects of GLP-1 on neonates is vital as GLP-1 is increasingly administered during pregnancy. This study evaluates the effect of GLP-1 exposure on maternal complications and neonatal defects in mice. Pregnant female A/J mice received subcutaneous injections of recombinant GLP-1 (rGLP-1; 1000 nmol/kg) on embryonic day 1 (EP, early pregnancy) or day 15 (E15, late pregnancy). Maternal and neonatal body weights, morphology, and mortality were recorded, and mRNA sequencing was conducted to analyze gene expression in neonatal tissues. Maternal body weight decreased following rGLP-1 exposure, and pups born to both the early and late exposure groups experienced significant weight loss. Pups in the late exposure group exhibited uniform skin detachment and a dramatically higher mortality rate than those born to the early exposure group. Further, RT-PCR analysis confirms the significantly increased expression of selected genes in the skin and associated pathogenesis. RNA sequencing of pups’ skin, brain, lung, and liver tissues from the late exposure group showed altered gene expression. Since maternal weight loss, increased neonatal mortality, and altered gene expression have been observed, GLP-1 receptor agonists (GLP-1RAs) should be avoided during pregnancy. Full article

Coronary artery disease (CAD) and its acute manifestation, myocardial infarction (AMI), remain significant global health burdens, with a substantial impact on morbidity and mortality, especially in individuals with Type 2 Diabetes Mellitus (T2DM). The interaction between hyperglycemia, endothelial dysfunction, inflammation, and thrombosis creates a complex pathological environment that contributes to the progression of CAD and its acute complications, including AMI. Over recent years, there has been a shift in the therapeutic approach to CAD, especially in T2DM patients, where pharmacologic agents originally developed for glycemic control have demonstrated notable cardiovascular benefits beyond glucose regulation. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are at the forefront of this paradigm shift. Initially, these agents were designed to improve glycemic control, but their broader cardiovascular protective effects have become increasingly evident, particularly in patients with CAD. This review aims to provide an in-depth exploration of the mechanistic underpinnings of these agents, the clinical data supporting their cardiovascular benefits, and their potential role for patients with CAD. Full article

Obesity is a well-established risk factor for both the incidence and poorer clinical outcomes of Breast Cancer (BC), particularly among hormone receptor-positive postmenopausal women. However, conventional weight loss interventions have yielded limited success in altering cancer prognosis. Recently, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, have emerged as effective pharmacologic agents for sustained weight loss and are under investigation in oncology. This narrative review synthesizes evidence linking obesity to poor BC prognosis and evaluates the therapeutic potential of GLP-1 RAs in this context. Mechanistically, obesity exacerbates tumor progression through hormonal imbalance, chronic inflammation, and adipokine and insulin signaling, targets that may be modifiable through weight reduction. GLP-1 RAs offer multiple benefits, such as appetite suppression, delayed gastric emptying, and enhanced insulin sensitivity. Clinical studies in BC patients have shown weight loss ranging from 2.3% to 5%, likely attenuated by concurrent endocrine therapy. Preliminary data suggest that GLP-1 RA use does not increase the risk of cancer recurrence and may reduce cardiovascular morbidity. However, prospective studies are needed to confirm long-term oncologic safety and efficacy. Disparities in access and cost remain barriers to widespread adoption. Nevertheless, GLP-1 RAs represent a promising adjunct to manage obesity among BC patients, potentially improving metabolic health and long-term cancer outcomes. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have evolved from glucose-lowering agents to transformative therapies across multiple organ systems. This comprehensive review synthesizes current evidence on the mechanisms, established applications, and emerging therapeutic frontiers of GLP-1 RAs. Methods: We conducted a systematic literature search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception through May 2025, using controlled vocabulary and free-text terms related to GLP-1 RAs, their mechanisms, and clinical applications. Results: GLP-1 RAs demonstrate pleiotropic effects through fundamental cellular mechanisms, including enhanced mitochondrial function, anti-inflammatory actions, improved cellular quality control, and comprehensive metabolic regulation. Established applications demonstrate robust efficacy in diabetes management (HbA1c reductions of 1.5–2.0%), obesity treatment (weight loss of 7–24%), and cardiovascular protection (14–20% reduction in major adverse cardiovascular events, or MACE). Emerging applications span neurological disorders, dermatological conditions, respiratory diseases, and novel applications in addiction medicine and autoimmune disorders. Conclusions: GLP-1 RAs represent a paradigmatic shift toward multi-system therapeutic intervention, with expanding evidence supporting their role as comprehensive metabolic modulators. Full article

The liver’s susceptibility to age-related diseases, including hepatocellular carcinoma (HCC), is increasingly linked to progressive epigenetic alterations that disrupt gene regulation, promote fibrosis, and impair regeneration. While glucagon-like peptide-1 receptor agonists (GLP-1RAs) are well-established in the treatment of type 2 diabetes and obesity, emerging evidence suggests they may also exert protective effects on the liver through the modulation of epigenetic pathways. In this perspective, we explore the hypothesis that GLP-1RAs may help restore a healthier epigenetic state in the aging liver by influencing mechanisms such as DNA methylation, histone modification, and non-coding RNA activity. These effects could reduce chronic inflammation, hepatic stellate cell activation, and fibrotic remodeling, key steps in the path to HCC. Preclinical studies have shown GLP-1RAs can affect transcriptional regulation and fibrotic markers, and early clinical data support improvements in liver function and structure in patients with metabolic liver disease. We highlight the need for further research to clarify these mechanisms in aging populations and propose that GLP-1RAs hold potential as a novel therapeutic strategy to reduce liver cancer risk by targeting the epigenetic contributors to disease progression. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes mellitus and obesity. However, their sustained effect on delaying gastric emptying raises new challenges in gastrointestinal endoscopy performed under sedation. This narrative review aims to summarize current evidence on the impact of GLP-1 RAs on gastric motility and to propose clinical strategies to mitigate associated procedural risks. Methods: A narrative review was conducted integrating findings from scintigraphy, capsule endoscopy, gastric ultrasound, and existing clinical guidelines. Emphasis was placed on studies reporting residual gastric content (RGC), anesthetic safety outcomes, and procedural feasibility in patients undergoing endoscopy while treated with GLP-1 RAs. Results: GLP-1 RAs significantly increase the prevalence of clinically relevant RGC, despite prolonged fasting, with potential implications for airway protection and sedation safety. Although the risk of pulmonary aspiration remains low (≤0.15%), procedural delays, modifications, or cancellations can occur in up to 30% of cases without adapted protocols. Several professional societies (AGA, ASGE, AASLD) advocate for individualized management based on procedure type, symptomatology, treatment phase, and point-of-care gastric ultrasound (POCUS), in contrast to the systematic discontinuation recommended by the ASA. Conclusions: Effective management requires personalized fasting protocols, risk-based stratification, tailored anesthetic approaches, and interprofessional coordination. We propose a clinical decision algorithm and highlight the need for training in gastrointestinal pharmacology, POCUS, and airway management for endoscopists. Future priorities include prospective validation of clinical algorithms, safety outcome studies, and the development of intersocietal consensus guidelines. Full article

Obstructive sleep apnea (OSA) syndrome is a severe, debilitating, and pervasive sleep disorder. OSA mainly affects people with obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia and is strongly associated with cardiovascular complications. Based on the bidirectional relationship between T2DM and OSA, the latter represents a risk factor for the former, and, vice versa, people with T2DM have a high risk of OSA. Mechanical and hormonal factors, inflammatory mediators, and a dysregulated autonomic nervous system contribute to the mechanisms underlying the disease. Treatment of OSA is necessary even if the available remedies are not always effective. In addition to traditional treatments, including lifestyle adaptations and bariatric surgery, CPAP equipment, i.e., a breathing device ensuring continuous positive pressure to keep the airways open during sleep, represents the most common treatment tool. More recently, pharmacological research has paved the way to newer seemingly effective therapeutic strategies involving, in particular, two hypoglycemic agent classes, i.e., sodium–glucose co-transporter 2 inhibitors (SGLT2-is) and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP1-ras). This narrative review provides an update on all of the above. Full article

Background: Type 2 diabetes mellitus (T2DM) increases sepsis risk due to immune dysfunction and chronic inflammation. Antidiabetic medications, while primarily used for glycemic control, may modulate sepsis susceptibility through immune and inflammatory pathways. This study investigates the association between antidiabetic medication use and sepsis risk in T2DM patients. Methods: A longitudinal cohort study was conducted using clinical registry data from 5009 T2DM patients at the University Hospital, Debrecen, Hungary (2016–2020). Sepsis cases were identified via ICD-10 code A41, and antidiabetic medication use was categorized using ATC codes. Baseline comorbidities and laboratory parameters were extracted. Chi-square and Wilcoxon rank–sum tests assessed associations between sepsis and categorical/numerical variables, respectively. Time-adjusted multivariate logistic regression evaluated predictors of sepsis risk, with odds ratios (ORs) and 95% confidence intervals (CIs) reported. Results: Age, hypertension, ischemic heart disease, nephropathy, elevated blood glucose, C-reactive protein, and creatinine also independently increased sepsis risk. Insulin use was associated with a 2.6-fold increased sepsis risk (OR = 2.6, 95% CI: 2.09–3.34, p < 0.001), while SGLT2 inhibitors (OR = 0.56, 95% CI: 0.34–0.91, p = 0.02) and GLP-1 receptor agonists (OR = 0.39, 95% CI: 0.19–0.79, p = 0.009) were protective. Conclusions: Insulin-treated patients may require closer infection monitoring, while SGLT2 inhibitors and GLP-1 RAs could be prioritized in high-risk individuals. These findings highlight the potential to inform risk stratification and guide personalized antidiabetic therapy to reduce sepsis risk in T2DM. Full article

Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) alleviate stress on multiple organs. SGLT2i has been demonstrated to benefit heart failure, hemodynamic regulation, and renal protection while GLP-1RA on the other hand has been shown to demonstrate a strong impact on glycemic management, weight loss, and atherosclerotic cardiovascular disease. This review will aim to understand and evaluate the mechanistic rationalization, clinical evidence, and the potential therapeutic treatment of SGLT2 inhibitors and GLP-1 receptor agonists to treat individuals who have CKM syndrome. This analysis also assesses whether combination therapy can be a synergistic approach that may benefit patients but is still underutilized because of the lack of clear guidelines, the associated costs, and disparities in accessibility. Therefore, in this review, we will be discussing the combination therapy’s additive and synergistic effects, current recommendations and clinical evidence, and mechanistic insights of these GLT2 inhibitors and GLP-1 receptor agonists in CKM syndrome patients. Overall, early and combination usage of GLP-1RA and SGLT2i may be essential to demonstrating a significant shift in modern cardiometabolic therapy toward patient-centered care. Full article

Sodium–glucose co-transporter-2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP-1 RAs) are now established as cornerstone therapies for patients with type 2 diabetes mellitus (T2DM), given their cardiovascular and renal protective properties. However, their use in patients with peripheral artery disease (PAD) remains controversial due to concerns raised in early trials about potential increases in lower limb complications, particularly amputations. This narrative review examines current evidence on the association between SGLT2is and GLP-1 RAs in PAD-related outcomes, including limb events, amputation risk, and cardiovascular and renal endpoints. Drawing from randomized controlled trials, real-world cohort studies, and systematic reviews, we provide an integrated perspective on the safety and utility of SGLT2is and GLP-1 RAs in individuals with PAD, highlight patient selection considerations, and identify areas for future investigation. Full article

Background and Aim: Type 2 diabetes (T2D) continues to pose a significant public health challenge worldwide. Among therapeutic options, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have proven effective in optimizing glycemic control and improving cardiometabolic profiles. Semaglutide, now available in an oral formulation, represents a modern strategy to improve patient adherence while supporting glucose and weight regulation. This study primarily investigated the effects of oral semaglutide on key metabolic indicators and secondary endpoints included cardiovascular risk markers (blood pressure and lipid profile) and patient-reported quality of life (QoL). Study Design and Methods: A longitudinal, prospective observational study was conducted involving patients with T2D across two Italian healthcare facilities. Participants were assessed at baseline (T0) and at three subsequent intervals—6 months (T1), 12 months (T2), and 18 months (T3)—following the initiation of oral semaglutide use. Key Findings: Out of 116 participants enrolled, 97 had complete and analyzable data. Across the 18-month follow-up, significant improvements were observed in glycemic parameters, with a notable reduction in HbA1c levels (T0 vs. T3, p = 0.0028; p ≤ 0.05, statistically significant). Self-reported outcomes showed enhanced quality of life, especially in treatment satisfaction and perceived flexibility (T0 vs. T3, p < 0.001). Conclusions: Daily administration of 14 mg oral semaglutide in individuals with T2D resulted in substantial benefits in glycemic regulation, weight reduction, cardiovascular risk management, and overall patient satisfaction. These findings reinforce its potential role as a sustainable and effective option in long-term diabetes care from both a clinical and public health perspective. Full article