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

## TL;DR

This paper explores why SGLT2 inhibitors do not consistently improve physical function in patients, despite other health benefits.

## Contribution

The study identifies physiological changes caused by SGLT2 inhibitors that may hinder physical function improvements.

## Key findings

- SGLT2 inhibitors alter energy homeostasis and pancreatic hormone levels.
- Changes in muscle metabolism and appetite regulation may prevent physical function improvements.
- Current evidence on SGLT2i effects on skeletal muscle and mobility is limited and incomplete.

## 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.