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,…
Background: Injectable peptide-based glucagon-like peptide-1 receptor (GLP1R) agonists (GLP1RAs) are effective treatments for obesity and diabetes but are limited by patient compliance and scalability challenges. In contrast, non-peptide small-molecule GLP1RAs offer the advantage of oral delivery but are relatively inactive…
Background & aim: Glucagon-like peptide-1 receptor agonists, such as semaglutide, induce substantial weight loss but may adversely affect muscle mass. This is of particular concern in older adults with obesity, who are vulnerable to sarcopenia. Accordingly, obesity treatments should be…
Background & aim: Translational rodent models of glomerulosclerosis are essential in drug discovery for chronic kidney disease (CKD). The anti-glomerular basement membrane (anti-GBM) model in mice represents a clinically relevant model as it exhibits key features of albuminuria and glomerulosclerosis.…
Background & aim: Transferrin receptor-1 (TfR1) transcytosis-mediated delivery of therapeutic monoclonal antibodies across the blood-brain barrier (BBB) is a promising concept in drug development for CNS disorders. In this study, we investigated brain delivery and effects on plaque burden of…
Background & aim: The current understanding of diabetic kidney disease (DKD) has significant gaps regarding the underlying pathogenesis. In this study, we aimed to characterize the temporal progression of DKD using a state-of-the-art mouse model of hypertension-accelerated disease, integrating kidney…
Background & aim: NLT-101 is a first-in-class compound that functions by proximity engagement with a target in the nuclear envelope that mediates its activity. NLT-101 is in preclinical development for metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis driven indications. The present…
Background & aim: The glucagon-like peptide-1 receptor (GLP-1R) and gastric inhibitory polypeptide receptor (GIPR) dual agonist tirzepatide is currently approved for the treatment of obesity and type 2 diabetes. In a recent phase 2b trial (SYNERGY-NASH) in patients with metabolic-dysfunction…
