Topical Metformin Lotion for Tendinopathy Prevention

The laboratory of Dr. James H-C. Wang at the University of Pittsburgh has demonstrated that a topically applied metformin lotion can prevent the onset of tendinopathy in a mechanically overloaded mouse model—revealing a promising, non-invasive strategy to reduce overuse tendon injuries that commonly affect athletes, workers, and military personnel. The study, published in Scientific Reports (2025), shows that localized metformin delivery mitigates inflammation and tissue degeneration while avoiding systemic drug exposure.

Tendinopathy is a widespread overuse injury affecting millions annually, including a large percentage of active-duty service members. Mechanical overload leads to chronic inflammation, matrix degradation, and functional loss. Current treatment options—such as rest, physical therapy, or corticosteroid injections—are reactive, not preventive, and carry potential side effects or compliance challenges. A portable, preventive, and non-invasive formulation such as this metformin lotion could be deployed at training bases or operational sites to protect against chronic injuries that compromise mission capability.

To address this, Dr. Wang’s MechanoBiology Laboratory, Bethel Musculoskeletal Research Center, Department of Orthopaedic Surgery, formulated a metformin-based topical lotion (ML) applied to the skin over the Achilles tendon prior to repetitive loading. The metformin lotion blocked the release of high-mobility group box 1 (HMGB1) protein from tendon cells, decreased systemic inflammatory markers (IL-1β, PGE₂), preserved collagen alignment, and enhanced AMPK activation while reducing profibrotic TGF-β₁ signaling. These combined effects helped maintain tendon homeostasis under high mechanical stress.

In controlled in-vivo studies, topical metformin application prevented histologic and biochemical signs of tendinopathy after four weeks of treadmill overuse. The lotion was well tolerated and demonstrated consistent tissue penetration and anti-inflammatory efficacy. Because metformin is already FDA-approved for other uses, this work supports rapid translational potential toward human studies in high-risk populations.

Supported in part by the Medical Technology Enterprise Consortium (MTEC) and the U.S. Department of Defense, this research aligns with the DoD priority to develop “Solutions to Accelerate Return-to-Readiness following Musculoskeletal Injuries.” Ongoing efforts include optimizing formulation stability, conducting pharmacokinetic and GLP safety studies, and preparing for early-phase human trials.