0233: Differential Effects of GLP-1 Receptor Agonists versus SGLT2 Inhibitors on Hypoglycemia and Infection Risk in Diabetic Patients with Inflammatory Arthritis

Background/Purpose: While both SGLT2 inhibitors and GLP-1 receptor agonists improve glycemic control in type 2 diabetes (T2D), their safety profiles, particularly regarding hypoglycemia and infection risk, may differ in patients with inflammatory conditions. This study compared these outcomes in patients with T2D and inflammatory polyarthropathy treated with either drug class.

Methods: This retrospective cohort study analyzed data from the TriNetX global health research network, identifying adult patients with T2D and inflammatory polyarthropathy receiving either SGLT2 inhibitors (n=3,377) or GLP-1 receptor agonists (n=4,733). After propensity score matching (n=2,838 per group), we evaluated the incidence of hypoglycemia, respiratory infections, urinary tract infections, sepsis, and other infection-related outcomes over a 5-year follow-up period.

Results: Patients treated with SGLT2 inhibitors experienced higher rates of sepsis (8.1% vs 5.9%, HR 1.609, 95% CI 1.318-1.965, p< 0.001) and acute kidney injury (16.9% vs 13.6%, HR 1.371, 95% CI 1.216-1.547, p< 0.001) compared to those on GLP-1 receptor agonists. Hypoglycemic events were more common in the SGLT2 inhibitor group (1.8% vs 1.1%, HR 1.594, 95% CI 1.028-2.472, p=0.036). The SGLT2 inhibitor cohort also showed higher rates of endocarditis/valve disorders (3.8% vs 2.9%, HR 1.478, 95% CI 1.098-1.990, p=0.043) and bacteremia (3.4% vs 2.4%, HR 1.627, 95% CI 1.205-2.196, p=0.001). Pneumonia incidence was similar between groups. Acute respiratory distress was more frequent with SGLT2 inhibitors (11.0% vs 6.7%, HR 1.699, 95% CI 1.480-1.949, p< 0.001).

Conclusion: In patients with T2D and inflammatory polyarthropathy, treatment with GLP-1 receptor agonists was associated with lower risks of serious infections, acute kidney injury, and hypoglycemia compared to SGLT2 inhibitors. These findings suggest that GLP-1 receptor agonists may offer a more favorable safety profile in this specific patient population. Clinicians should consider these differences when selecting glucose-lowering agents for patients with T2D and inflammatory arthritis.