# Metformin Administration Protects Against Deltoid Tendon Damage Through Activation of Notch Signaling

## TL;DR

Metformin, a diabetes drug, may protect tendons by activating a key signaling pathway, offering new therapeutic benefits beyond blood sugar control.

## Contribution

This study reveals metformin's novel role in protecting tendons via Notch signaling activation in diabetic and aged models.

## Key findings

- Metformin-treated T2DM patients showed lower tendon surgery rates and improved tendon structure.
- Metformin upregulates HES1 and downregulates MMP3, indicating tendon protection through Notch signaling.
- Metformin activates Notch signaling in tenocytes from diabetic mice and aged monkeys.

## Abstract

Type 2 Diabetes Mellitus (T2DM) is a growing global health concern that is associated with severe complications including diabetic tendinopathy. In this study, we found that T2DM patients had a significantly higher prevalence of tendon surgery compared to non‐T2DM patients, which were alongside impaired ECM and cell adhesion. Notably, metformin‐treated T2DM patients had a lower prevalence of tendon surgery compared to other medications, along with improved tendon fiber structure, downregulation of tendon damage marker MMP3, and upregulation of HES1, a Notch signaling effector gene. Metformin also activates Notch signaling in cultured tenocytes, and tendons from diabetic mice and aged monkey. These findings highlight metformin's potential to protect tendons by activating Notch signaling, offering novel insights into its therapeutic benefits beyond glucose regulation.