Exploring Pathophysiological Processes Shared Between Type 2 Diabetes Mellitus and Osteoarthritis

Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are highly prevalent chronic disorders with increasing global burdens that frequently coexist and share common risk factors, including obesity, aging and chronic low-grade inflammation. This narrative review aims to summarize current evidence regarding the epidemiological, clinical and molecular links between T2DM and OA and to highlight potential therapeutic implications. Growing evidence suggests that T2DM contributes to OA development and progression through multiple interconnected mechanisms. These include advanced glycation end-product (AGE) accumulation, oxidative stress, chronic inflammation, extracellular matrix degradation, impaired autophagy, ferroptosis, mesenchymal stem cell dysfunction and microvascular impairment within joint tissues. In addition, shared genetic and molecular pathways, including AGE-RAGE, IL-17, PI3K/Akt/mTOR and LGR6/Wnt/β-catenin/NRF2 signaling, further support a biological connection between the two diseases. Clinically, T2DM is associated with increased OA severity, enhanced pain sensitization, accelerated disease progression and higher rates of joint arthroplasty. Emerging evidence also suggests that antidiabetic agents, particularly metformin and glucagon-like peptide 1 receptor agonists, may exert disease-modifying effects through anti-inflammatory, metabolic and chondroprotective mechanisms. Overall, T2DM and OA should be regarded as interconnected metabolic-inflammatory disorders. Improved understanding of their shared mechanisms may facilitate earlier intervention, therapeutic repurposing and integrated multidisciplinary management strategies to reduce disease burden and improve patient outcomes.