Fecha de publicación: -- Fuente: PubMed "nature biotechnology" Mol Ther Adv. 2026 Oct 15;34(4):201868. doi: 10.1016/j.omta.2026.201868. eCollection 2026 Dec 10.ABSTRACTCystic fibrosis (CF) is a life-threatening autosomal recessive disease caused by loss-of-function mutations in the CF transmembrane conductance regulator (CFTR) gene. Although highly effective CFTR modulator therapies (HEMT) have transformed outcomes for many individuals, substantial unmet needs remain, and CF-related metabolic diseases are increasingly recognized as an important therapeutic frontier. Emerging evidence, including our recent work in the CF rabbit model, implicate sodium-glucose cotransporters (SGLTs) as key contributors to CF pathophysiology. This review provides an overview of SGLT biology and the therapeutic use of SGLT inhibitors in metabolic diseases. It summarizes preclinical studies of SGLTs in CF, which have shown that SGLT1 is upregulated in CF human airway epithelial cells and across disease-relevant tissues in CF rabbits in a mutation-independent manner, and that pharmacological SGLT blockade with dual SGLT1/2 inhibitors such as sotagliflozin attenuates endoplasmic reticulum (ER) stress, reduces tissue pathology, and improves survival of CF rabbits. This review calls for expanded preclinical research and future clinical trials to evaluate SGLT1-potent inhibitors as adjunctive therapies to CFTR modulators. As a mutation-agnostic, multi-systemic approach, SGLT1 inhibition holds potential for addressing the extrapulmonary and metabolic manifestations of CF.PMID:42999678 | PMC:PMC13743517 | DOI:10.1016/j.omta.2026.201868