Research Hub
The living record of
peptide science.
PubMed studies synced daily. Active clinical trials. Evidence updates when the science materially changes. Monthly synthesis for practitioners.
Layer 1
Study feed
Predicted 10-Year Cardiovascular Disease Risk Reduction with Tirzepatide Use Over Three Years for Primary Prevention of Cardiovascular Disease in Obesity.
Eur J Prev Cardiol
Naveed Sattar, Mamas Mamas, Runjia Li +7 more
This post hoc analysis assessed the durability of tirzepatide for primary cardiovascular disease (CVD) prevention in obesity, based on predicted CVD risk, in the SURMOUNT-1 (SM-1) 3-year study.
Insulin Resistance and Cutaneous Squamous Cell Carcinoma: A Narrative Review of Molecular Mechanisms.
Iran J Med Sci
Dedi Ardinata, Tengku Ibnu Alferraly, Ariyati Yosi +1 more
Although the association between diabetes and cutaneous squamous cell carcinoma (cSCC) is well recognized, the specific role of insulin resistance (IR) as an independent driver of cSCC pathogenesis remains underexplored. This review synthesized emerging evidence on the ultraviolet (UV)-independent molecular mechanisms by which IR promotes cSCC initiation and progression. Hyperinsulinemia activates the insulin-like growth factor-1 receptor (IGF-1R), which triggers both the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathways, stimulating keratinocyte proliferation and suppressing apoptosis. In parallel, hyperglycemia-driven formation of advanced glycation end products (AGEs) and oxidative stress cause deoxyribonucleic acid (DNA) damage and impair tumor suppressor functions, notably that of tumor protein p53 (TP53). The resulting reactive oxygen species (ROS) activate nuclear factor-kappa B (NF-κB), establishing a chronic inflammatory milieu that remodels the tumor microenvironment through cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and by upregulating matrix metalloproteinases (MMPs). These processes collectively facilitate the malignant transformation of actinic keratosis (AK) to invasive cSCC. The analysis in the present study identified novel therapeutic targets and reaffirmed the importance of further studies on microbiome interactions and lifestyle interventions for IR-associated cSCC.
Acromegaly Secondary to Ectopic Growth Hormone-Releasing Hormone Secretion From Metastatic Bronchial Carcinoid Tumor: A Case Report.
Cureus
Samreen F Anees, Irfaan A Abid
Bronchial carcinoid tumors are malignant neuroendocrine tumors that typically arise from enterochromaffin cells found in the epithelial lining of the lungs. We report a case of a 62-year-old female who was diagnosed with an atypical bronchial carcinoid tumor and subsequently underwent left pneumonectomy in December 2002. A year later, the patient developed metastases to the liver, bone, and pancreas. Over the subsequent decade, she developed clinical features of acromegaly and had persistently elevated insulin-like growth factor 1 (IGF-1) levels. Further investigation of the metastatic lesions revealed ectopic production of growth hormone-releasing hormone (GHRH). The patient underwent multiple cycles of chemotherapy for her metastatic lesions. She also continues to require long-term therapy with octreotide (Sandostatin) and pegvisomant to control IGF-1 levels. This case highlights the rarity of ectopic GHRH secretion from metastatic bronchial carcinoid tumors and emphasizes the importance of long-term surveillance and multidisciplinary management.
Glucagon-Like Peptide-1 (GLP-1)-Based Therapies and Heart Failure Outcomes: A Scoping Review of Contemporary Randomized Controlled Trials.
Cureus
Jenika Patel, Deep Patel, Maria Pino
Glucagon-like peptide-1 (GLP-1)-based therapies have been observed to produce cardiovascular benefits in cardiometabolic diseases; however, their impact on heart failure-specific outcomes is only becoming known through dedicated randomized controlled trials (RCTs). This scoping review consolidates the most recent randomized data that examine how GLP-1-based therapies affect heart failure-specific symptoms, functional capacity, and the occurrence of clinical events. Literature searches were conducted in PubMed, Google Scholar, and CINAHL for RCTs and prespecified analyses between 2021 and 2026 evaluating GLP-1-based therapies and reporting heart failure-specific outcomes. Five RCT-based studies met inclusion criteria, including randomized trials and prespecified RCT-derived analyses evaluating semaglutide and tirzepatide. Among patients with heart failure with preserved ejection fraction (HFpEF) and obesity, semaglutide significantly improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and 6-minute walk distance compared to placebo. Tirzepatide exhibited improvements across symptoms and functional and event-based outcomes, with prespecified trajectory analyses confirming favorable shifts in New York Heart Association functional class, Patient Global Impression of Severity, health-related quality of life, and background heart failure medication use. Among patients with type 2 diabetes mellitus and chronic kidney disease, semaglutide was associated with a significantly reduced rate of cardiovascular death or worsening heart failure events. Although the available evidence comes from a small number of recent randomized and prespecified RCT-based studies, current findings suggest that GLP-1-based therapies are associated with improvements in symptoms and functional capacity and reductions in heart failure events in certain patient populations, especially those with HFpEF and obesity. These beneficial effects support a potential role for the integration of GLP-1-based therapies in population-specific heart failure management.
Microfluidic-assisted formulation of hydrophobic ion pairing-Based solid lipid nanoparticles for semaglutide delivery.
Int J Pharm
Ilaria Arduino, Rosa Maria Iacobazzi, Alessia Pontrelli +6 more
Semaglutide is a glucagon-like peptide-1 receptor agonist widely used for the treatment of type 2 diabetes and obesity. Despite its clinical efficacy, oral administration remains challenging because of its limited gastrointestinal stability, poor epithelial permeability, and low affinity for lipid-based delivery systems. In the present study, a combined hydrophobic ion pairing (HIP) and solid lipid nanoparticle (SLN) approach was explored to improve semaglutide incorporation and delivery-related properties. Semaglutide was complexed with the cationic lipid DOTAP at different molar ratios (1:0-1:18) and subsequently incorporated into cetyl palmitate-based SLNs produced by microfluidic mixing using a herringbone device. The resulting formulations were characterized in terms of particle size, ζ-potential, encapsulation efficiency, morphology, solid-state organization, colloidal stability, release behavior, mucus interaction, cytocompatibility, and epithelial permeability. Among the various formulations prepared, the one prepared with a molar ratio semaglutide: DOTAP of 1:18 and a peptide concentration of 10% (w/w) (F10) showed the best results, combining particle sizes of less than 300 nm with almost complete encapsulation efficiency and a highly positive ζ-potential. FTIR, DSC, TGA and SAXS analyses confirmed the correct formation of the complex and its incorporation into the lipid matrix. The F10 formulation demonstrated good stability under simulated gastrointestinal conditions and a sustained-release profile. The formulation also exhibited strong interactions with mucus, whilst retaining the ability to diffuse through the mucin network. Cytocompatibility studies demonstrated acceptable cell viability at relevant concentrations, whilst permeability experiments through Caco-2 monolayers revealed an approximately 6-fold increase in apparent permeability compared to free semaglutide. Therefore, these findings indicate that the combination of DOTAP-mediated hydrophobic ion pairing and microfluidic-assisted SLN production represents a potentially promising strategy for improving semaglutide encapsulation, gastrointestinal stability, and epithelial transport, while maintaining a favorable balance between mucus interaction and mucodiffusion.
Acute Unilateral NAION following Tirzepatide Therapy: A Case Report.
Case Rep Ophthalmol
Jela Valášková, Dmytro Bondarchuk, Peter Kadlic +2 more
Dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists, such as tirzepatide, have significantly advanced the management of type 2 diabetes mellitus and obesity. However, emerging safety signals have raised concerns regarding rare ocular adverse events.
Trends in glucagon-like peptide-1 receptor agonist utilization and expenditure in Croatia.
J Int Med Res
Andrej Belančić, Marta Kučan Štiglić, Almir Fajkić +5 more
IntroductionGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes and obesity by improving glycemic control, promoting weight loss, and reducing cardiovascular risk. This study aimed to evaluate national trends in GLP-1 RA utilization and expenditure in Croatia between 2010 and 2024.MethodsWe conducted a nationwide, retrospective analysis using the International Medical Statistics and IQVIA pharmaceutical databases. Utilization was measured in defined daily doses per 1000 inhabitants per day, and financial expenditure was expressed in euros. Trends were contextualized within evolving clinical evidence, guideline recommendations, and healthcare reimbursement policies.ResultsTotal noninsulin antidiabetic drug consumption more than doubled between 2010 and 2024, with the use of GLP-1 RAs rising from negligible at the time of market entry to that worth 15.99 defined daily doses per 1000 inhabitants per day in 2024, representing 16.1% of total prescriptions. Expenditure on GLP-1 RAs reached 42.07 million euros in 2024, accounting for 42.7% of total noninsulin antidiabetic spending. Semaglutide emerged as the dominant agent according to both utilization and cost, followed by dulaglutide and liraglutide. Obesity-specific indications were underutilized, largely due to lack of reimbursement.ConclusionsGLP-1 RA prescribing has increased substantially in Croatia over the past decade, reflecting their growing therapeutic importance. However, economic constraints, restrictive reimbursement, and sociocultural barriers continue to limit access, particularly in obesity care. Our findings highlight the need to align reimbursement frameworks and clinical practice with emerging evidence to maximize the cardiometabolic and public health benefits of GLP-1 RAs.
Risk of Dementia after initiation of GLP-1 RA versus long-acting insulin in patients with type 2 Diabetes mellitus.
J Prev Alzheimers Dis
Chien-Hung Lin, Peir-Haur Hung, Mu-Chi Chung +2 more
Recent studies suggest a decreased risk of dementia in patients treated with glucagon-like peptide-1 receptor agonist (GLP-1 RA). In this study, we compare the risk of dementia associated with GLP-1 RA versus long-acting insulin in adults aged over 50 years with type 2 diabetes (T2DM) using real-world administrative data from a large Taiwan cohort DESIGN: A population-based retrospective cohort study SETTING: We analyzed 10,783 propensity score-matched pairs of adults with T2DM who initiated either GLP-1 RA or long-acting insulin from Taiwan's National Health Insurance Research Database (2011-2021).
Impact of GLP-1 Analogue Therapy on Gastrointestinal Outcomes in Patients with Irritable Bowel Syndrome: A Real-World TriNetX Analysis.
Dig Dis Sci
Sajjad Ahmed Khan, Anurag Marasini, Alisha Shrestha +7 more
Glucagon-like peptide-1 (GLP-1) receptor agonists are increasingly prescribed for diabetes and obesity, conditions that frequently coexist with irritable bowel syndrome (IBS). Their effects on gastrointestinal motility and visceral sensitivity raise the possibility of therapeutic benefit in IBS, but real-world evidence remains limited. This study evaluated the association between GLP-1 receptor agonist initiation and subsequent gastrointestinal outcomes in patients with IBS using a large federated electronic health records network.
A Review of Randomized Controlled Trials for Vitiligo Therapies Published Between 2013 and 2023.
Cureus
Natalia Maverakis Ramirez, Zachary J Jaeger, Delphine J Lee
Vitiligo is a depigmentation disorder whose treatment remains a serious challenge. While it is generally accepted that topicals and phototherapy are helpful for generalized symmetric disease, randomized controlled trials (RCTs) provide the best evidence for treatment. Our objective was to identify and summarize RCTs for vitiligo from 2013 to 2023. A systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO) was performed per PRISMA guidelines. We searched CENTRAL, ClinicalTrials.gov, Embase, PubMed, and Web of Science for RCTs using keywords such as 'vitiligo' and/or 'treatment' or 'intervention.' A total of 652 studies underwent full-text review, and 151 studies met the inclusion criteria. We focused our study on RCTs using the vitiligo area scoring index (VASI) as the primary outcome measure, leading to 36 studies. We further narrowed our focus to studies that could be aggregated into the intervention categories: phototherapy and systemic combination therapy (n=10), topical and topical combination therapy (n=15), and systemic monotherapy (n=5).  Treated versus control subjects showed statistically improved VASI after the following interventions were added to phototherapy: oral psoralen, oral minipulsed prednisone, implanted afamelanotide, topical ethyl vanillate, topical bimatoprost, and oral vitamins A and E. Effective topical therapies were ruxolitinib, calcipotriol and betamethasone, tacrolimus and mometasone, and microdermabrasion and tacrolimus. None of the systemic monotherapies was superior to their corresponding comparator.
Suppression of early pro-inflammatory senescent signature post-radiotherapy mitigates chronic bone damage.
J Bone Miner Res
David Achudhan, Jacob Orme, Ritika Sharma +8 more
Cellular senescence has been implicated in the pathophysiology of radiotherapy-associated bone loss. Based on our previous work, clearance of senescent cells using genetic and pharmacological tools alleviates the anomalies associated with radiation-associated bone deterioration. The pro-inflammatory senescence associated secretome referred to as senescence associated secretory phenotype (SASP), is a hallmark of cellular senescence. The modulation of SASP by senomorphic drugs, potentially can suppress the pro-inflammatory secretome of senescent cells, irrespective of the underlying senescence mechanism. In this study we tested a senomorphic drug, ruxolitinib, a Janus kinase inhibitor (JAKi), during acute and chronic radiotherapy related effects on the bone. Our clinical data indicate an early increase in several pro-inflammatory SASP proteins following radiotherapy of spinal metastasis in prostate cancer patients. Longitudinal assessment of SASP-related genes confirmed this acute elevation in several SASP markers in systemic circulation following irradiation of male mouse femurs. In studies done in male mice, following three preclinical radiotherapy regimens of 30Gy (5 x 6Gy), 60Gy (5 x 12Gy) and a single dose of 24Gy, suppression of SASP by JAKi was efficacious in suppressing radiation-induced bone damage. In comparison and as shown before, the senolytic combination of D+Q was also able to alleviate radiation-associated bone loss. Early and intermittent suppression of SASP using JAK inhibitors in male mice alleviated chronic bone deterioration, diminished telomere dysfunction, lowered senescence and SASP marker expression and reduced bone-marrow adiposity. Overall, our study shows that early targeting of SASP proteins could be a potential therapeutic to prevent radiotherapy-related chronic bone loss and risk of fractures.
Comparative reproductive toxicity of 6:2 FTS and PFOS in female zebrafish (Danio rerio): From histopathology to molecular response.
Ecotoxicol Environ Saf
Zehui Zhang, Dandan Huang, Bai Gao +7 more
6:2 Fluorotelomer sulfonate (6:2 FTS), a substitute for perfluorooctane sulfonate (PFOS), is frequently detected in aquatic environments, yet its reproductive toxicity remains incompletely understood. In this study, 480 adult female zebrafish were randomly assigned to five groups: DMSO control, PFOS (0.25 and 5 μg/L), and 6:2 FTS (0.25 and 5 μg/L), with 96 fish per group and three replicate tanks. After 42 days of exposure, PFAS bioaccumulation was assessed using three fish per group; separate sets of six fish per group were used for ovarian oxidative stress, HPG-axis-related hormones, HPG-axis-related gene expression, and reproductive performance; ovarian histopathology was examined using four fish per group; offspring development was assessed using 120 embryos per group; and integrated biomarker response version 2 (IBRv2) was applied. Data are presented as mean ± SEM, with significance set at p < 0.05. Compared with PFOS, 6:2 FTS showed lower bioaccumulation in the maternal liver, ovary, brain, and offspring, but still exhibited relative accumulation in ovarian tissue. Moreover, the ovarian oxidative stress induced by 6:2 FTS was relatively mild. Both compounds disrupted HPG-axis function, increasing gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) levels while decreasing follicle-stimulating hormone (FSH), testosterone (T), and estradiol (E2) levels. Consistently, gnrh-family genes and lhβ were upregulated, whereas fshβ and 17β-hsd were downregulated. These endocrine disturbances were associated with abnormal oocyte development, increased follicular atresia, reduced spawning output, and higher offspring malformation risk. IBRv2 analysis indicated that although 6:2 FTS caused lower overall toxicity than PFOS, it still impaired reproduction mainly through HPG-axis disruption. These findings demonstrate the reproductive risk of 6:2 FTS and support careful safety evaluation of PFAS alternatives.
Case Report: Oral semaglutide-associated depression in a patient with type 2 diabetes mellitus: a dose-dependent recurrence confirmed on rechallenge and managed with vortioxetine-bupropion combination therapy.
Front Psychiatry
Abdulrahman S Alanazi, Basmah A Alanazi
Oral semaglutide carries a neuropsychiatric safety profile that continues to evolve. Large clinical trials have not, at the group level, demonstrated excess psychiatric adverse events-but pharmacovigilance databases and case reports have documented a signal for depression and suicidal ideation in individual patients. A dose-dependent onset with rechallenge has not, to our knowledge, been previously described for the oral formulation, though such an association cannot be established from a single observation.
Incretin analogues as cardiovascular agents: a state-of-the-art review.
Front Endocrinol (Lausanne)
Diego Araiza-Garaygordobil, Jorge Rico-Fontalvo, Betsabe Hernández-Balbuena +2 more
Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist tirzepatide have evolved over the past decade from glucose-lowering antidiabetic agents into a cardiovascular drug class with proven outcome benefit across multiple clinical scenarios. This state-of-the-art review synthesizes the cardiovascular evidence base for incretin analogues, organized by clinical scenario, and addresses the structural challenges that constrain their deployment in low- and middle-income countries (LMICs). We review the pharmacology and proposed cardiovascular mechanisms, including direct effects on the vascular endothelium, macrophage inflammation, and epicardial adipose tissue, alongside indirect benefits mediated by weight loss, glycemic control, and blood pressure reduction. We summarize the evidence in five clinical scenarios: type 2 diabetes with established atherosclerotic cardiovascular disease or high cardiovascular risk; overweight or obesity with established cardiovascular disease but without diabetes; obesity-related heart failure with preserved ejection fraction; chronic kidney disease; and symptomatic peripheral artery disease. Pipeline agents (retatrutide, CagriSema, survodutide, orforglipron, zenagamtide, and MariTide) are reviewed alongside their ongoing cardiovascular outcome trials. A dedicated section examines the global access perspective, including the disproportionately high burden of cardiometabolic disease in LMICs, the limited representation of regional populations in pivotal trials, and the structural barriers of cost and reimbursement that constrain access. We close with a practical algorithm for the clinician, an honest assessment of evidence gaps, and a calibrated outlook on the next generation of incretin-based cardiovascular therapy.
Retrospective implementation of BSE age-specific NT-proBNP criteria for triage of suspected heart failure.
Br J Cardiol
Andrew Chisom Madu, Brian Li, Daniela Toumazi +5 more
Measuring the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) can help to triage patients with suspected acute heart failure (HF), towards confirmatory transthoracic echocardiography. It has a high negative-predictive value, however, it is not specific due to the influence on its levels by comorbidities. The British Society of Echocardiography (BSE) have published criteria for the triage of those with suspected HF, for inpatient echocardiography, using age-specific NT-proBNP cut-off values. This study aims to evaluate the diagnostic utility of these recommendations for triaging inpatient echocardiography requests to diagnose acute HF. We analysed data from consecutive inpatients who had an echocardiogram requested between 1 and 15 March 2024, at two secondary care hospitals in the East of England. NT-proBNP results were paired to these requests. Patients were then grouped into the three BSE NT-proBNP cut-off levels and compared. The main outcome of interest was the diagnostic yield for HF using these criteria. There were 159 patients included in the final analysis: 100 (62.9%) met the NT-proBNP BSE threshold; 65 (65.0%) of these had an inpatient echocardiogram, of which 39 (60.0%) were diagnosed with HF. There were 59 (37.1%) who did not meet the BSE threshold: 29 (49.2%), however, had an inpatient echocardiogram, with nine (31.0%) subsequently diagnosed with HF. Review of these nine patients revealed other valid reasons for echocardiography request: therefore, no cases were truly missed. Patients who had atrial fibrillation (AF) had a similar diagnostic yield for HF compared with those who did not (AF + HF diagnosis 54.0% vs. no AF + HF 67.9%; p=0.385). In conclusion, the BSE's age-related NT-proBNP criteria for inpatient echocardiography provides a safe and viable framework for triaging inpatient requests towards a diagnosis of HF. This approach could reduce the burden on stretched services, allowing resources to be directed more appropriately.
Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis.
Lancet Diabetes Endocrinol
Johannes F E Mann, Sunil V Badve, Florian M M Baeres +18 more
The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials.
Dysregulated neuroendocrine stress response and blood pressure management burden are linked to remote diffusion-weighted imaging lesions after intracerebral hemorrhage: a prospective pilot study.
Hypertens Res
Motohiro Okumura, Takeo Sato, Yuki Tsujimoto +12 more
Remote diffusion-weighted imaging lesions (RDWILs) after intracerebral hemorrhage (ICH) are associated with unfavorable outcomes and reflect secondary microvascular injury in the setting of systemic stress responses and autonomic dysfunction due to ICH. However, association of RDWILs with neuroendocrine stress markers and acute blood pressure (BP) control remain unclear. We evaluated whether stress hormone levels and the duration of intravenous nicardipine infusion, as an index of post-ICH BP management burden, were associated with RDWILs. Patients with ICH enrolled in a prospective study (October 2020-December 2022) were analyzed. RDWILs were defined as diffusion restriction located ≥ 10 mm from the hematoma. Plasma concentrations of the hypothalamic-pituitary-adrenal (HPA) axis markers-adrenocorticotropic hormone and cortisol-and the sympathetic-adrenomedullary (SAM) axis markers-dopamine, adrenaline, noradrenaline, and urinary total metanephrine-were measured in the subacute phase. Post-ICH BP management burden was indexed by days of intravenous nicardipine required to achieve and maintain systolic BP < 140 mmHg. Among 39 patients (median age 54 years; 67% male), 7 (18%) had RDWILs. In unadjusted analyses, dysregulated HPA-axis- (lower adrenocorticotropic hormone and higher cortisol) and higher SAM-axis-related stress markers (higher dopamine, noradrenaline, and urinary total metanephrine), and longer nicardipine duration were significantly associated with RDWILs. These associations were consistent in exploratory adjusted models. Dopamine, noradrenaline, and urinary total metanephrine were also positively associated with nicardipine infusion duration. Dysregulated HPA-axis- and higher SAM-axis-related stress markers, and longer nicardipine duration were each associated with RDWILs. Higher SAM-axis-related stress markers were also associated with post-ICH BP management burden.
Delayed growth of SK-ES-1 Ewing sarcoma tumor xenografts is associated with reduced Trk and IGF1R pathway markers.
Oncotarget
Bruna Almeida Dos Santos, Nat xE Lia Hogetop Freire, Livia Fratini +10 more
Copyright: &copy; 2026 dos Santos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Ewing sarcoma (ES) is an aggressive childhood tumor. We have previously shown that tropomyosin receptor kinase (Trk) neurotrophin receptors regulate viability, and the Trk and multi-kinase inhibitor K252a restores sensitivity to chemotherapy, in ES cells. Here, we show that administration of K252a in mice transiently delays ES tumor growth and reduces expression and phosphorylation of multiple targets. BALB/c nu/nu nude mice inoculated with SK-ES-1 ES cells were given daily intraperitoneal (i.p.) injections of K252a for 18 days. Immunohistochemical analysis of tumors was performed to quantify the expression and phosphorylation of Trk receptors, phosphoinositide 3-kinase (PI3K), and insulin-like growth factor 1 receptor (IGF1R). Treatment with K252a led to a partial and transient delay in ES tumor growth and reduced the expression and phosphorylation of TrkA, TrkB, PI3K, and IGF1R. Combined treatment with K252a and the IGF1R inhibitor NVP-ADW742 was more effective in reducing ES cell viability than each compound alone. Associations between genes encoding Trks, PI3K, and IGF1R and overall survival (OS) in patients with ES was examined. Significant associations between expression of NTRK genes and patient OS were found, indicating that NTRK genes should be further evaluated as biomarkers for prognosis in patients with ES.
The new era of MASH pharmacotherapy: a comprehensive review of FDA-approved and emerging agents.
Front Gastroenterol (Lausanne)
Abeer Qasim, Rayan Alataa, Fnu Veena +1 more
Metabolic dysfunction-associated steatohepatitis (MASH), formerly nonalcoholic steatohepatitis (NASH), is a progressive liver disease and a leading cause of cirrhosis and liver-related mortality worldwide, affecting approximately 3%-5% of the global adult population and up to 30%-40% of individuals with type 2 diabetes mellitus (T2DM) or those attending dedicated diabetes and endocrine centers. For decades, treatment was limited to lifestyle interventions. The years 2024 and 2025 marked a paradigm shift with the first-ever FDA approvals of pharmacologic agents for MASH.
Diagnostic and Management Pitfalls of SGLT2 Inhibitor-Associated Ketoacidosis in the ICU: Lessons Following Cardiac Surgery and GLP-1 Agonist Interaction.
Case Rep Crit Care
Ana Paula García Pérez, Damián Gutiérrez-Zárate, Karina Rosas-Sánchez +2 more
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are cornerstones in the treatment of Type 2 diabetes (T2D), but their use is associated with diabetic ketoacidosis (DKA), a potentially life-threatening complication in the critical care setting. We present two cases of male patients with T2D who developed SGLT2i-associated ketoacidosis under different stressors: the first following coronary artery bypass graft (CABG) surgery and the second after the addition of semaglutide to his therapeutic regimen. Both patients presented with high anion gap metabolic acidosis, ketonuria, and plasma glucose levels < 200 mg/dL. Management required intravenous insulin protocols and glucose supplementation to reverse ketosis. This report emphasizes the need for preoperative suspension protocols and close monitoring of changes in combination therapy to avoid diagnostic delays in the intensive care unit.