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

Year: 2025

Type: article

Abstract: 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.

Source: Frontiers in Systems Biology

DOI: 10.3389/fsysb.2025.1593229

Authors: Cian Sutcliffe, Jack A. Sargeant, Thomas Yates, Melanie J. Davies, Luke A. Baker

Institutions: University of Leicester, National Institute for Health and Care Research, NIHR Leicester Biomedical Research Centre

Language: English

Topic: Diabetes Treatment and Management

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,353