Work

SGLT1 inhibition in cystic fibrosis: From preclinical evidence to clinical potential

Year: 2026

Type: review

Abstract: ) 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.

Source: Molecular Therapy Advances

DOI: 10.1016/j.omta.2026.201868

Authors: Xiubin Liang, Yang Liu, Shijing Jia, Kezhong Zhang, Jie Xu

Institutions: University of Michigan, Michigan Medicine, Wayne State University

Language: English

Topic: Cystic Fibrosis Research Advances

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases