Comparison of Sodium-Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide-1 Receptor Agonists and Risks of Osteoarthritis and Arthroplasty in Patients With Type 2 Diabetes Mellitus: A Propensity Score-Matched Cohorts Retrospective Study

Diabetes Metab Res Rev. 2025 Jul;41(5):e70051. doi: 10.1002/dmrr.70051.

Abstract

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) may have the potential to lower the risk of osteoarthritis through an anti-inflammatory mechanism. This study compared the risks of new-onset osteoarthritis and joint replacement surgery between new users of SGLT2is and new users of glucagon-like peptide-1 receptor agonists (GLP-1 RAs).

Materials and methods: We conducted a propensity score-matched cohort retrospective study by using data obtained from the TriNetX platform. The Global Collaborative Network of TriNetX includes approximately 131 million patients from 109 health care organisations. First, new users of SGLT2is and GLP-1 RAs among patients with type 2 diabetes mellitus were identified. Two homogeneous groups were established through propensity score matching. The study outcomes were the risks of new-onset osteoarthritis and joint replacement surgery of the hip or knee. Hazard ratios (HRs) along with 95% CIs were calculated using the TriNetX platform.

Results: Initially, the SGLT2is and GLP-1 RA groups comprised 51,177 and 52,977 patients, respectively. After matching, each group comprised 37,676 patients. The mean age of the patients was 59.5 years. Approximately 45% of the patients in both groups were women. The SGLT2is group had significantly lower risks of new-onset osteoarthritis (HR: 0.951; 95% CI: 0.916-0.988) and joint replacement surgery (HR: 0.703; 95% CI: 0.550-0.898) than the GLP-1 RA group.

Conclusions: SGLT2is use was associated with reduced risks of new-onset osteoarthritis and joint replacement surgery compared with GLP-1 RA use in patients with type 2 diabetes mellitus. Future prospective studies are warranted to confirm our findings.

Keywords: arthroplasty; glucagon‐like peptide‐1 receptor agonists; osteoarthritis; sodium‐glucose cotransporter 2 inhibitors.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Arthroplasty* / statistics & numerical data
  • Arthroplasty, Replacement* / statistics & numerical data
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Follow-Up Studies
  • Glucagon-Like Peptide-1 Receptor Agonists*
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis* / epidemiology
  • Osteoarthritis* / etiology
  • Osteoarthritis* / prevention & control
  • Prognosis
  • Propensity Score
  • Retrospective Studies
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucagon-Like Peptide-1 Receptor Agonists