CHP-281

CHP-281 is a potent and highly selective small molecule inhibitor of the sodium-glucose cotransporter 1 (SGLT1), developed by Chugai Pharmaceutical. Unlike SGLT2 inhibitors that primarily act in the kidneys to promote glucose excretion, CHP-281 targets SGLT1 in the brush border membrane of the small intestine, where it is responsible for the absorption of dietary glucose and galactose. By inhibiting this transporter, CHP-281 delays and reduces intestinal glucose absorption, thereby blunting postprandial glycemic excursions. Furthermore, the presence of unabsorbed glucose in the distal small intestine triggers the release of incretin hormones, such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), from enteroendocrine L-cells. This dual mechanism—local inhibition of glucose uptake and systemic enhancement of incretin secretion—makes CHP-281 a candidate for the treatment of type 2 diabetes mellitus and metabolic disorders such as obesity. Research has demonstrated its efficacy in improving glucose tolerance and reducing body weight in preclinical models.