Background & aim: Dyslipidemia, characterized by hyper-cholesterolemia and hypertriglyceridemia, is a central component of metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis. While being highly instrumental in drug development, preclinical models of MASH often fail to recapitulate a human-like lipoprotein profile. To enhance…
Background & aim: Histopathological fibrosis staging is a key endpoint in preclinical drug development for MASH. However, the MASH CRN (Kleiner) system assigns one global stage per biopsy, potentially obscuring subtle treatment-related collagen remodelling and tissue heterogeneity. We developed an…
Background & aim: Aims: Survodutide is a novel long-acting dual glucagon (GCGR)/glucagon-like peptide-1 (GLP-1R) receptor agonist currently in phase-3 clinical development for the treatment of people living with obesity and metabolic dysfunction-associated steatohepatitis. Emerging evidence suggests impaired renal GCGR function…
Background & aim: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in preclinical models of neurodegeneration, with emerging evidence suggesting these effects may be driven by modulation of neuroinflammation. However, the cellular mechanisms underlying GLP-1RA effects on neuroinflammation remain poorly…
Background & aim: Chronic myocardial injury over weeks to months drives cellular hypertrophy and extracellular matrix remodeling, culminating in heart failure with preserved ejection fraction (HFpEF). Traditional 2D histological sectioning may miss or misrepresent the true spatial heterogeneity of localized…
Background & aim: The long-acting glucagon-like peptide-1 (GLP1) receptor agonist semaglutide was recently approved as the first GLP-1–based therapy for people with MASH and moderate-to-severe fibrosis. Clinical studies have demonstrated that semaglutide not only improves liver histology but also reverses…
Background & aim: Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as promising therapeutic candidates for metabolic dysfunction-associated steatohepatitis (MASH). Importantly, semaglutide was recently approved as the first GLP-1-based treatment for people with MASH with moderate-to-severe fibrosis. Translational models that recapitulate…
Background & aim: Glucagon influences kidney function through both direct intrarenal glucagon receptor (GCGR) signaling and indirect humoral pathways. Increasing evidence suggests that renal GCGR activity is impaired in chronic kidney disease (CKD). Survodutide is a novel, long-acting dual GCGR/GLP-1…
Background & aim: Long-acting amylin analogues offer mechanistic complementarity to incretin-based therapies for obesity. Accordingly, CagriSema, a fixed-dose combination of the amylin analogue Cagrilintide and the GLP-1 analogue Semaglutide, has demonstrated superior weight loss compared with either agent alone in recent clinical trials…
Background & aim: Obesity pharmacotherapy has significantly improved weight management, with semaglutide (GLP-1 receptor agonist), tirzepatide (dual GLP-1 and GIP receptor agonist) and survodutide (dual glucagon/GLP-1 receptor agonist) demonstrating substantial efficacy in reducing body weight. These drugs primarily act by…