Gout-Related Medication Use After Initiating Sodium Glucose Co-Transporter-2 Inhibitors in Patients with Gout and Type 2 Diabetes: Population-Based Target Trial Emulation Studies.

Objectives: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower serum urate and are associated with lower risk of recurrent gout flares. We used target-trial emulation to compare rates of allopurinol initiation and use of anti-inflammatories (high-dose glucocorticoids, NSAIDs, colchicine) and diuretics (prototypic serum urate-raising medication) among patients with gout using SGLT2i versus dipeptidyl peptidase-4 inhibitors (DPP-4i; primary comparator), with glucagon-like peptide-1 receptor agonists (GLP1-RA) as an alternative comparator. Research Design and Methods: From a general population database, we identified patients with gout and comorbid type 2 diabetes and used Cox proportional hazards and Poisson regressions with inverse probability of treatment weighting to emulate randomisation to SGLT2i or DPP-4i/GLP1-RA. We also replicated the analysis in an EHR dataset with further adjustment for serum urate and BMI. Results: Among 26,739 adults with gout and type 2 diabetes (mean age 66), 67% had polypharmacy. Allopurinol initiation was lower among SGLT2i initiators than DPP-4i, with hazard ratio 0.62 (95% CI: 0.52, 0.73). Associations were stronger among those using diuretics at baseline (p-interaction=0.03) and persisted when comparing SGLT2i to GLP1-RA, and accounting for serum urate and BMI in the secondary dataset. SGLT2i was also associated with lower rates of high-dose glucocorticoid, NSAID, colchicine, and diuretic dispensing, with rate ratios of 0.78 (0.74, 0.83), 0.85 (0.80, 0.92), 0.87 (0.83, 0.92), and 0.87 (0.85, 0.89), respectively. Conclusions: For patients with gout and type 2 diabetes, SGLT2i may reduce gout-related medication use, which could, in turn, reduce exposure to the harmful cardiovascular-kidney-metabolic effects of NSAIDs and glucocorticoids in this high-risk population.