SGLT2 Inhibitors Reduce Risk of New Gout Diagnoses in T2D Relative to Sulfonylurea

Natalie McCormick, PhD
Credit: American College of Rheumatology

An analysis of data from a population-level database of type 2 diabetes patients from British Columbia, Canada offers further insight into the benefits of SGLT2 inhibition on risk of gout in people with type 2 diabetes.

With evidence supporting the urate lowering effect of SGLT2 inhibitors in patients with type 2 diabetes, the study builds on previous research from the investigatory team, which was led by Natalie McCormick, PhD, an epidemiologist at Massachusetts General Hospital and Harvard Medical School.¹

“Consistent with their known urate-lowering effects, [SGLT2 inhibitors] may reduce gout risk for those who need a second-line agent after metformin and provide an attractive option to simultaneously address the high burden of gout and cardiometabolic sequelae in patients with diabetes,” wrote investigators.¹

McCormick has led a number of studies examining the effects of SGLT2 inhibitors in patients with gout, including a study at EULAR 2023 assessing risk of recurrent gout flares among people with type 2 diabetes using SGLT2 inhibitors from. In this study, rate of gout flares was lower with SGLT2 inhibitor initiation (52.4 events per 1000 person-years) than with 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).²

The current research endeavor from McCormick and colleagues was designed to further illustrate the effect of SGLT2 inhibitors in patients with type 2 diabetes by examining effects of use within a sequential, propensity score-matched, new-user comparative effectiveness study leveraging data from a Canadian general population database and using target trial emulation framework. The database used by investigators was the Population Data BC database, which is a series of linked administrative databases of all provincially funded emergency department and outpatient medical visits and hospital discharges as well as all dispensed prescriptions in British Columbia, Canada.¹

The primary outcome of interest for the study was incident gout, which was defined as an emergency department visit or hospitalization with a primary discharge diagnosis or an ICD-9/10 code of gout during an outpatient encounter with intra-articular or oral corticosteroids, colchicine, or NSAIDs dispensed within 7 days. Investigators planned to perform Cox proportional hazards and Poisson regressions with 1:1 propensity score matching for their primary analysis, with overlap weighting used as part of the study’s sensitivity analysis.¹

For inclusion in the trial, patients were required to be at least 18 years or older with type 2 diabetes whose first-ever dispensing for SGLT2 inhibitors or sulfonylurea occurred from January 2014 through June 2022. investigators required patients to have a current prescription for metformin at the time of dispensing no prior dispensing of other glucose-lowering medications. Investigator pointed out this analysis excluded patients with a gout diagnosis or dispensing of a gout-specific medication, such as allopurinol, febuxostat, probenecid, or colchicine, unlike their analysis of recurrent gout flares, which included patients with existing gout at baseline.¹

Overall, 34,604 propensity score-matched adults initiating SGLT2 inhibitors or sulfonylurea were identified for inclusion in the study. This cohort had a mean age of 60 (Standard Deviation [SD], 12.4) years, 60% were male, and the mean follow-up was 1.38 years.¹

During the follow-up, there were 105 incident gout cases among the SGLT2 inhibitor cohort (4.27 per 1000 person-years), compared with 159 cases among the 17,302 propensity score-matched patients who initiated sulfonylurea (6.91 per 1000 person-years; This corresponded to an adjusted Hazard Ratio (aHR) of 0.62 (95% CI, 0.48 to 0.80) and RD of −2.6 (95% CI, −4.0 to −1.3) per 1000 person-years. In their sensitivity analysis, application of overlap weighting in place of 1:1 propensity-score matching resulted in an aHR of 0.68 (95% CI, 0.54 to 0.85) and an RD of −2.0 (95% CI, −3.6 to −0.5).¹

Investigators called attention to an analysis of cardiovascular outcomes in their study. These results suggested use was associated with reduced risk of major adverse cardiovascular events (HR, 0.87; 95% CI, 0.77 to 0.98; and RD, −3.58; 95% CI, −6.19 to −0.96) as well as a reduced risk of heart failure.¹

Investigators highlighted multiple limitations in their study to consider before overinterpretation of results. These included the observational nature of the study, inability to access measures for HbA2c, uric acid, or kidney function tests, and lack of data related to race and ethnicity of patients included.¹

“The gout and cardiovascular benefits associated with [SGLT2 inhibitors] in these target trial emulations may guide selection of glucose-lowering therapy in patients with [type 2 diabetes] who are at risk for (or already have) gout needing a second-line agent after metformin,” investigators wrote.¹

References:

1. McCormick N, Yokose C, Lu N, et al. Sodium-Glucose Cotransporter-2 Inhibitors vs Sulfonylureas for Gout Prevention Among Patients With Type 2 Diabetes Receiving Metformin. JAMA Intern Med. Published online April 15, 2024. doi:10.1001/jamainternmed.2024.0376
2. Campbell P. SGLT2 inhibitors could lower risk of recurrent gout flares in people with diabetes. HCP Live. June 4, 2023. Accessed April 18, 2024. https://www.hcplive.com/view/sglt2-inhibitors-could-lower-risk-of-recurrent-gout-flares-in-people-with-diabetes.