Comparative effects of SGLT2 inhibitors and GLP-1 receptor agonists on osteoarthritis risk in patients with type 2 diabetes mellitus: A multi-institutional cohort study

Objectives Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated metabolic and anti-inflammatory benefits, which may influence the risk of osteoarthritis (OA) in patients with type 2 diabetes mellitus (T2DM). However, their comparative impact on OA incidence remains unclear. This study aimed to evaluate and compare the effects of SGLT2 inhibitors and GLP-1 RAs on the risk of developing OA in patients with T2DM. Methods A retrospective cohort study was conducted using the TriNetX database, including adults with T2DM who were newly prescribed either SGLT2 inhibitors or GLP-1 RAs between January 2017 and December 2019. After propensity-score matching, 452,445 patients were included in each group. The primary outcome was OA incidence over five years. Secondary outcomes included knee OA, hip OA, total knee arthroplasty (TKA), total hip arthroplasty (THA), and major joint injections. Results The SGLT2 inhibitor group had a significantly lower risk of OA compared with the GLP-1 RAs group (HR, 0.921; 95% CI, 0.895–0.946), with a greater reduction observed for knee OA (HR, 0.831; 95% CI, 0.783–0.882). No significant differences were observed in THA or TKA risk. SGLT2 inhibitor users also had fewer major joint injections (HR, 0.915; 95% CI, 0.882–0.951). Conclusions Among patients with T2DM, SGLT2 inhibitors were associated with a lower risk of OA, particularly knee OA and joint injections, compared to GLP-1 RAs. These findings support further investigation into the potential association between SGLT2 inhibitor use and lower OA-related outcomes.