Exploring the disconnect: mechanisms underpinning the absence of physical function improvement with SGLT2 inhibitors

Current evidence suggests sodium-glucose cotransporter 2 inhibitors (SGLT2i) do not consistently improve patient physical function, despite improvements in clinical symptoms and reductions in both adiposity and body weight. We highlight heterogenous methodologies in SGLT2i physical function trials....

Full description

Saved in:
Bibliographic Details
Main Authors: Cian Sutcliffe, Jack A. Sargeant, Thomas Yates, Melanie J. Davies, Luke A. Baker
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Systems Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fsysb.2025.1593229/full
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Current evidence suggests sodium-glucose cotransporter 2 inhibitors (SGLT2i) do not consistently improve patient physical function, despite improvements in clinical symptoms and reductions in both adiposity and body weight. We highlight heterogenous methodologies in SGLT2i physical function trials. We then provide context to these findings by collating new data which describes how reduced glycaemia with SGLT2i alters numerous physiological processes and discuss how these alterations may diminish or prevent expected functional improvements. Alterations include changes to energy homeostasis, pancreatic hormones, muscle metabolism, physical activity, and appetite regulation. Current evidence in humans is limited and the mechanistic interaction between SGLT2i, skeletal muscle, and physical function remains incompletely understood. Future investigations must embed comprehensive molecular techniques within suitably designed clinical trials to determine how skeletal muscle health and patient mobility is influenced by acute and long term SGLT2i prescription.
ISSN:2674-0702