(A-126) GLP-1 Receptor Agonists and Risk of Osteoarthritis Among Patients with Type 2 Diabetes: A Population-Based Cohort Study

Background: Type 2 diabetes (T2D) increases the risk of osteoarthritis, with both conditions sharing common risk factors including obesity. Glucagon-like peptide-1 receptor agonists (GLP1RA) might regulate osteoarthritis via their weight-reducing and anti-inflammatory effects. Nevertheless, whether the use of GLP1RA is associated with a lower risk of incident osteoarthritis (OA) among patients with T2D remains uncertain.

Objectives: To assess the association between the use of GLP1RA and the risk of OA among patients with T2D

Methods: We conducted a nationwide, population-based cohort study applying a target trial emulation framework. From the National Health Insurance Service database (2010 - 2022) of Korea, eligible patients included adult T2D patients who initiated GLP1RA or dipeptidyl peptidase-4 inhibitors (DPP4I). The index date was defined as the date of study drug initiation. The primary outcome was a composite OA, comprising knee, hip, and hand OA, and secondary outcomes were the individual components of primary outcome, along with incident joint replacement (JR). Applying as-treated approach, patients were followed from the index date until the earliest of outcome occurrence, discontinuation, switching, all-cause death, or study end date (31 Dec 2022). Propensity score fine stratification weighting was applied to balance the covariate distributions between treatment groups. Incidence rates per 100 person-years (IRs) and hazard ratios (HR) with 95% confidence intervals (CIs) were estimated using Poisson regressions and Cox models, respectively. We repeated our analysis by stratifying patients into obese and non-obese, with cutoff value of body mass index 25 kg/m2, to assess possible effect modification.

Results: Among a total of 2 056 824 eligible patients, 9 866 patients started GLP1RA (mean age 45 yrs; 55% male; 67% dulaglutide) and 2 047 158 patients started DPP4I (mean age 56 yrs; 70% male). After weighting, during mean follow-up of 621 days, IR for OA were 3.99 (95% CI, 3.54 – 4.48) and 4.36 (4.34 – 4.38) among GLP1RA and DPP4I users, respectively. Compared to DPP4I, GLP1RA was not associated with a lower risk of OA (HR 0.93, 95% CI, 0.83 – 1.05). The results for the secondary outcomes were consistent with the primary outcome (HR 1.16 [0.52 – 2.59] for JR; 0.92 [0.78 – 1.09] for knee OA; 1.20 [0.62 – 2.34] for hip OA; 4.06 [0.98 – 16.75] for hand OA). We did not find significant effect modification by obesity (obese: HR 0.94 [0.79 – 1.12]; non-obese: 0.88 [0.63 – 1.22]; p for interaction 0.56).

Conclusions: In this nationwide cohort study, the use of GLP1RA was not associated with a lower risk of OA among patients with T2D. Although GLP1RA regulated OA symptoms in obese and osteoarthritic population, they did not prevent OA in patients with T2D.