SGLT1 inhibition in cystic fibrosis: From preclinical evidence to clinical potential.
- 1Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
- 2Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
- 3Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Abstract
Cystic 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.
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BibTeX
@article{liang2026sglt1,
title = {{SGLT1 inhibition in cystic fibrosis: From preclinical evidence to clinical potential.}},
author = {Xiubin Liang and Yang Liu and Shijing Jia and Kezhong Zhang and Jie Xu},
journal = {Molecular therapy. Advances},
year = {2026},
month = oct,
doi = {10.1016/j.omta.2026.201868},
url = {https://europepmc.org/article/MED/42999678},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - SGLT1 inhibition in cystic fibrosis: From preclinical evidence to clinical potential.
AU - Xiubin Liang
AU - Yang Liu
AU - Shijing Jia
AU - Kezhong Zhang
AU - Jie Xu
PY - 2026
DA - 2026/10/15
JO - Molecular therapy. Advances
DO - 10.1016/j.omta.2026.201868
UR - https://europepmc.org/article/MED/42999678
AB - Cystic 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.
SN - 3117-387X
ER -