SGLT2is Reduce Recurrent Gout Flare More Than DPP-4is in Patients With Diabetes, Study Says

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) may reduce recurrent flares and gout-primary emergency department (ED) visits and hospitalizations for patients with type 2 diabetes (T2D) and gout, according to a study published in Annals of Internal Medicine.

The study’s primary outcome was recurrent gout flares, for which data was pulled from ED, hospitalization, outpatient, and medication dispensing records. Secondary outcomes included myocardial infarction (MI), stroke, genital infection, and osteoarthritis incidence. The study authors compared these outcomes among people with T2D and gout initiating SGLT2is to the outcomes of people initiating dipeptidyl peptidase 4 inhibitors (DPP-4is), another second-line glucose-lowering agent that has not been associated with serum urate levels or cardiovascular risk.

After propensity score matching 1:1, the study included 4075 patients initiating SGLT2is and 4075 patients initiating of DPP-4is, with a mean follow-up of 1.6 years. Most participants (71%) were male and the mean age at baseline was 66 years. Empagliflozin and linagliptin accounted for the majority of SGLT2i and DPP-4i prescriptions, respectively.

Propensity score matching showed a lower gout flare rate among patients taking SGLT2is compared with patients taking DPP-4i, with 52.4 and 79.7 events per 1000 person-years, respectively. This finding reflects a rate ratio (RR) of 0.66 (95% CI, 0.57-0.75) and a rate difference (RD) of -27.4 (95% CI, -36.0 to -18.7) per 1000 person-years, marking nearly 28 fewer gout flare events per 1000 person-years among the SGLT2i group compared with the DPP-4i group.

The authors also found lower rates of gout-primary ED visits and hospitalizations among the SGLT2i group, with an RR of 0.52 (95% CI, 0.32-0.84) and RD of 3.4 (95% CI, -5.8 to -0.9) per 1000 person-years.

“The lower flare rate appeared during the first year of use of SGLT2is (without apparent paradoxical flares) among persons without prior urate-lowering gout therapy; the protective association persisted among demographic subgroups and regardless of diuretic or urate-lowering gout therapy use,” the authors noted. “The absolute risk reduction tended to be larger among persons not using urate-lowering therapy at baseline and was substantially greater among patients with greater gout intensity.”

Looking at secondary outcomes, patients initiating SGLT2is were 31% less likely to experience MI (HR, 0.69; 95% CI, 0.54 to 0.88) than patients initiating DPP-4is, with an RD of -7.6 (95% CI, -12.4 to -2.8) per 1000 person-years. Additionally, patients in the SGLT2i group were 19% less likely to experience a stroke (HR, 0.81; 95% CI, 0.62-1.05).

However, in contrast, SGLT2is were associated with higher risk for genital infections (HR, 2.15; 95% CI, 1.39-3.30) and did not seem to affect the risk of osteoarthritis, as the authors had anticipated (HR, 1.07; 95% CI, 0.95-1.20). These findings were similar when the authors applied propensity score overlap weighting.

“These findings suggest that SGLT2is could have a much-needed ability to simultaneously reduce the burden of recurrent gout flares and coronary sequelae in patients with gout and type 2 diabetes,” the authors said. "Given the pleiotropic cardiometabolic benefits associated with SGLT2is among patients with type 2 diabetes, this class of medications may be a particularly attractive addition to our current urate-lowering therapies to simultaneously address the high burden of gout and cardiometabolic sequelae,” they later added.

Reference

McCormick N, Yokose C, Wei J, et al. Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent gout flares and gout-primary emergency department visits and hospitalizations: a general population cohort study. Ann Intern Med. Published online July 25, 2023. Accessed July 27, 2023. doi:10.7326/M23-0724