More Evidence Backs Gout Benefit for Gliflozin Agents

MILAN — Canadian patients taking sodium-glucose cotransporter-2 (SGLT-2) inhibitors for type 2 diabetes saw reductions in rates of incident gout, ranging from about 40% to 60% relative to three other classes typically added to metformin, a researcher reported here.

With data covering some 100,000 type 2 diabetes patients in British Columbia, hazard ratios for developing gout with SGLT-2 inhibitor treatment were 0.54 versus dipeptidyl peptidase-4 (DPP-4) inhibitors, 0.39 versus glucagon-like peptide-1 (GLP-1) analogs, and 0.61 versus sulfonylurea agents, all of which were highly significant, according to Natalie McCormick, PhD, of Massachusetts General Hospital in Boston.

Similar patterns were seen for patient subgroups stratified by age, sex, and co-treatment with diuretics, McCormick told attendees at the European Alliance of Associations for Rheumatology (EULAR) annual meeting.

The findings aren’t a surprise. SGLT2 inhibitors such as dapagliflozin (Farxiga) and empagliflozin (Jardiance) were found to reduce serum urate — high levels of which are gout’s basic cause — in early trials. That, of course, suggested a benefit in gout risk. Although the disease mechanisms in type 2 diabetes and gout aren’t directly related, the conditions share many risk factors, such that the likelihood of having one is markedly higher if an individual also has the other.

A subsequent observational study confirmed an association between SGLT-2 inhibitor therapy and lower gout incidence. However, McCormick explained, the degree to which metformin treatment, which is common but not universal in type 2 diabetes, might have confounded those data was unknown, as use of the drug wasn’t systematically tracked.

Study Details

Consequently, her group believed it necessary to examine SGLT-2 inhibitors among patients who were all taking metformin. The team drew on data from British Columbia’s universal healthcare system, in which all dispensed prescription drugs are recorded along with standard clinical and utilization data. In particular, the researchers focused on patients with ICD-9/10 codes for diabetes who started second-line medications (SGLT-2 or DPP-4 inhibitors, GLP-1 analogs, or sulfonylureas) from 2014 through 2021 after having been on metformin.

Primary endpoint events indicating gout onset include emergency department visits or hospital admissions for gout or a gout-coded drug prescription. As a check on the data quality, McCormick and colleagues also counted mycotic genital infections and osteoarthritis diagnoses; higher rates of the former would be expected in patients receiving SGLT-2 inhibitors versus the other medication classes, while rates of the latter should not differ. (And indeed, both were confirmed.)

Each of the three comparison groups matched the SGLT-2 inhibitor users with those given other medications by baseline factors including age, sex, disease duration, rates of major diabetic complications, and previous healthcare utilization. Thus, in the group with DPP-4 inhibitors as the comparator, mean age was 61, 58% were men, diabetes duration was 10 years, and roughly half had a major complication such as retinopathy. (In the interest of time, McCormick didn’t show all the baseline data for the other groups; she said they were similar except that women were more likely to receive GLP-1 analogs as opposed to the other comparator drugs.)

Overall, some 52,000 patients were given SGLT-2 inhibitors, about 13,000 received DPP-4 inhibitors, 5,000 took GLP-1 analogs, and 42,000 were put on sulfonylureas.

McCormick acknowledged that these were administrative data that did not cover all potential confounding variables. But the overall thrust of the data matched the previous findings, and she cited the “consistency across subgroups” and the fact that the data were population-based, thus “enhancing the generalizability.” She also said follow-up was more than twice as long as in the previous U.S.-based study.