3D AI-Mapping of the HFpEF Heart: Does semaglutide remodel cardiac structure?
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…
Semaglutide improves metabolic and histological outcomes and reverses clinically relevant biomarker alterations in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH
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…
Therapeutic efficacy, biomarker signatures, and translatability of semaglutide in the liver biopsy-confirmed GAN DIO-MASH mouse model
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…
Survodutide, a novel dual GLP-1 receptor/glucagon receptor agonist, improves kidney health in a mouse model of advanced diabetic kidney disease
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…
Superior Efficacy and Clinical Translatability of CagriSema Compared to Cagrilintide and Semaglutide in the DIO rats
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…
Differential effects of semaglutide, tirzepatide, and survodutide on energy expenditure in obese mice under thermoneutrality
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…
A Multimodal Rat Brain Atlas and Whole-Brain Imaging Pipeline for Mapping Satiety Pathways and Anti-Obesity Drug Effects
Background & aim: Central regulation of appetite and satiety engages neuronal populations distributed across the brain. The identification of novel drug targets, development of anti-obesity therapeutics, and validation of their mode of action benefit from whole-brain imaging. Light-sheet fluorescence…
Survodutide acts through circumventricular organs in the brain and activates neuronal regions associated with appetite regulation
Abstract: Survodutide is a novel GCG/GLP-1 receptor (GCGR/GLP-1R) dual agonist in clinical development for people with obesity and people with metabolic dysfunction-associated steatohepatitis (MASH). Preclinically, survodutide demonstrated body weight lowering efficacy through decreased energy intake and increased energy expenditure. Here,…