Deep learning-enhanced 3D imaging unveils semaglutide impact on cardiac fibrosis
Background & aim: Myocardial fibrosis (MF), a hallmark of structural cardiac remodelling, drives disease progression across most forms of heart failure and plays a central role in heart failure with preserved ejection fraction (HFpEF). Despite its clinical relevance, effective treatments…
Renal transcriptomic profiling reveals beneficial effects of semaglutide and lisinopril in advanced diabetic kidney disease
Background & aim: Obesity, hyperglycemia and hypertension are critical risk factors for development of diabetic kidney disease (DKD). While emerging evidence suggests that glucagon-like peptide-1 receptor (GLP1R) agonists improve cardiovascular and renal outcomes in type 2 diabetes patients, their mode…
Reproducible and clinically translatable hepatoprotective effects of tirzepatide in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH
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…
Systemic inhibition of soluble TNF significantly changes glial cell populations leading to improved myelin integrity and better functional outcome after experimental stroke
Background & aim: Tumor necrosis factor (TNF) is highly upregulated after ischemic stroke and plays a crucial role in shaping the neuroinflammatory response that follows. Therapies aimed at inhibiting detrimental soluble (sol)TNF-TNF receptor 1 (TNFR1) signaling are gaining interest as…
Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide
Background & aim: Nutrient-stimulated gut hormone peptide YY3e36 (PYY3e36) selectively activates the neuropeptide Y2 receptor (NPY2R) and reduces energy intake in humans. We describe the discovery and pharmacology of the long-acting NPY2R agonist BI 1820237 and its potential bodyweight-lowering efficacy…
Proof-of-concept testing of semaglutide in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH
Background & aim: The long-acting glucagon-like peptide-1 (GLP-1) analogue semaglutide is approved for the treatment of type 2 diabetes and obesity. Recently, semaglutide has been reported to improve liver histopathological outcomes in patients with metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis…
Superior Hepatoprotective Effects of OPK-88006, a Novel GLP-1/Glucagon receptor dual agonist, to Semaglutide and Survodutide in the GAN Diet-Induced Obese and Biopsy-Confirmed Mouse Model of MASH
Background & aim: OPK-88006 is a novel peptide-based, long-acting glucagon-like peptide-1 receptor (GLP1R)/glucagon receptor (GCGR) dual agonist in current preclinical development for metabolic diseases, including obesity and metabolic dysfunction-associated steatohepatitis (MASH). The present study aimed to compare the therapeutic profile…
Tirzepatide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH-HCC with advanced fibrosis
Background & aim: The glucagon-like peptide-1 receptor (GLP1R) 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…