Publication:

Modulation of the gut-brain axis through selective inhibition of the sodium-glucose cotransporter type 1: physiological and therapeutic implications

The sodium-glucose cotransporter type 1 (SGLT1) is fundamental in intestinal glucose absorption. Its selective inhibition modulates the gut-brain axis by increasing carbohydrate delivery to the distal ileum, which stimulates the secretion of incretins such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) by enteroendocrine L-cells. Objectives were to analyze the physiological bases and clinical evidence of gut-brain axis modulation through SGLT1 inhibition, as well as its therapeutic implications. Systematic literature review (2019-2026) in PubMed, Scopus, and Cochrane regarding SGLT1 kinetics, incretin release, postprandial glycemic control, and the safety profile of selective and dual inhibitors. Intestinal SGLT1 inhibition delays glucose absorption, triggering a sustained endogenous release of GLP-1 and PYY. This afferent signaling, mediated by the vagus nerve to hypothalamic centers, promotes early satiety. Clinically, inhibitors like sotagliflozin demonstrate efficacy in reducing postprandial hyperglycemia and inducing weight loss. The gastrointestinal safety profile is associated with controlled malabsorption that favorably modifies microbiota composition. SGLT1 inhibition represents a comprehensive therapeutic approach. By activating the physiological pathways of the gut-brain axis, it offers significant benefits in metabolic control, positioning itself as a promising strategy for diabetes and obesity management.