SGLT2 Inhibitors Could Lower Risk of Recurrent Gout Flares in People with Diabetes

For people with type 2 diabetes, initiating therapy with an SGLT2 inhibitor could reduce risk of recurrent gout flares, according to a new study from the European Congress of Rheumatology (EULAR) 2023 annual meeting.

A new-user, active comparator cohort study, which leveraged data from more than 8000 patients with gout and type 2 diabetes, results of the study suggest initiation of SGLT2 inhibitors was associated with a 34-point difference in rate ratio for recurrent gout flares relative to their counterparts initiating therapy with DPP-4 inhibitors.

Few therapies have experienced the rapid ascent into treatment algorithms across as wide of a range of conditions as the SGLT2 inhibitor class. Just 10 years from the initial approval as an adjunct to diet and exercise for improving glycemic control in type 2 diabetes in March 2013, agents in the class have risen from adjunct for glycemic control to a guideline-recommended medication for heart failure as well as chronic kidney disease. In analyses of these trials, evidence emerged of a potential orate-lowering effect as a result of use.²

The EULAR 2023 study was launched by Natalie McCormick, PhD, Massachusetts General Hospital and Harvard Medical School and colleagues, citing an interest in further exploring this apparent orate-lowering effect and its potential impact on rate of recurrent flares. With this in mind, investigators designed their research endeavor as a new-user, active comparator cohort study leveraging data obtained from administrative health databases from British Columbia, Canada.1

From the administrative health data, investigators obtained information related to all dispensed prescriptions, regardless of funder, from their period of interest, which was defined as January 2014-June 2022. After propensity score-matching investigators identified a cohort of 8150 gout patients with type 2 diabetes for inclusion in their study. This cohort had a mean age of 68 years, 71% were male, and 59% had a history of cardiovascular disease.

The primary outcome of interest for the study was recurrent gout flare counts, which were identified emergency department, hospitalization, outpatient, and medication dispensing records. Investigators pointed out Poisson and Cox proportional hazards models were used to assess for risk of the primary outcome. Additionally, investigators noted plans to stratify results by sex, age, gout intensity, and use of diuretic and orate-lowering therapy.

Upon analysis, results indicate the rate of gout flares was lower with SGLT2 inhibitor initiation (52.4 events per 1000 person-years) than DPP-4 initiation (79.7 events per 1000 person-years), which correlates to a rate ratio (RR) of 0.66 (95% confidence interval [CI], 0.57 to 0.75) and a rate difference (RD) of —27.4 (95% CI, —36.0 to —18.7). When assessing for flares requiring hospitalization or emergency department visit, results of the investigators' analysis indicated the RR was 0.52 (95% CI, 0.32 to 0.84) and the RD was —3.4 (95% CI, —5.8 to —0.9) in favor of SGLT2 initiation.

Investigators pointed out results of their analyses were consistent across subgroups defined by age or sex, with the RR consistent regardless of baseline gout intensity or diuretic or orate-lowering therapy use. Investigators also pointed out the RD was greater in patients with greater gout intensity. Analysis of secondary endpoints of interest suggested SGLT2 initiation was associated with a lower risk of stroke and myocardial infarction, but an increased risk of genital infections relative to DPP-4 inhibitor initiators.¹

With an interest in learning more about the study and its implications, the editorial team of HCPLive Rheumatology sat down with McCormick to discuss the results of the EULAR 2023 study.

Dr. McCormick has no relevant disclosures to report.

1. McCormick N, Yokose C, Wei J, et al. INITIATION OF SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS AND RECURRENT GOUT FLARES IN GOUT PATIENTS WITH TYPE 2 DIABETES: A GENERAL POPULATION-BASED COHORT STUDY. Paper presented at: European Congress of Rheumatology (EULAR) 2023. Milan, Italy. May 31 – June 3, 2023.
2. Campbell P, Iapoce C. 10 years of SGLT2 inhibitors: A Decade of Redefining Cardiometabolic Care. HCP Live. March 29, 2023. Accessed June 2, 2023. https://www.hcplive.com/view/10-years-of-sglt2-inhibitors-a-decade-of-redefining-cardiometabolic-care.