Natalie McCormick, PhD, of the Rheumatology and Allergy Clinical Epidemiology Research (RACER) Center within the Division of Rheumatology in the Mass General Brigham Department of Medicine, is the lead author of a paper published in Diabetes Care, " Gout-Related Medication Use After Initiating Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Gout and Type 2 Diabetes: Population-Based Target Trial Emulation Studies ."
Q: What challenges or unmet needs make this study important?
Gout, a type of inflammatory arthritis caused by a buildup of uric acid (urate) in the body, affects 5.1% of U.S. adults (over 12 million), including 10% of those aged 65 or older. Urate is produced by the body when breaking down compounds called purines and normally dissolves in the blood, but when levels are high, they can precipitate out as monosodium urate crystals which can deposit in the joints. In addition to acutely painful joint flares and damage, gout often occurs alongside cardiovascular-kidney-metabolic (CKM) conditions . For example, one in four U.S. adults with gout also has type 2 diabetes and this same statistic applies to gout and chronic kidney disease.
Conventional urate-lowering therapies (ULTs) are recommended for flare prevention, but they don't help with the CKM comorbidities, making it necessary for patients with co-occurring conditions to take medications in different classes to treat both. This makes treatment decisions more complex, while increasing pill burden for patients and the potential for drug interactions.
Q: What central question(s) were you investigating?
Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are approved for the treatment of type 2 diabetes, heart failure and chronic kidney disease, and have also been shown to decrease serum urate levels and the need for diuretic medications (a major risk factor for gout flares). Therefore, we wondered, could SGLT2i use by patients with gout reduce their need for conventional ULTs and acute flare medications, including NSAIDs, colchicine and high-dose glucocorticoids?
The latter would be particularly attractive since patients with gout tend to be at high risk for the cardiovascular, gastrointestinal, kidney and metabolic adverse effects of these flare medications.
Q: What methods or approach did you use?
We emulated a randomized clinical trial using large, population‑based datasets. We captured over 18,000 patients with diagnoses of gout and type 2 diabetes who filled a new prescription for a glucose-lowering treatment—either SGLT2i, dipeptidyl peptidase 4 inhibitors (DPP-4i) or glucagon-like peptide 1 receptor agonists (GLP1-RA)—and were not currently using ULTs.
We used statistical techniques to balance baseline characteristics between treatment groups (for example, demographics, number of recent gout flares, etc.), thus mimicking randomization. We then followed patients over time to compare the probability of individuals in each treatment arm starting ULTs, as well as rates of gout flares and prescriptions for gout flare treatments and diuretics.
Q: What did you find?
Compared to DPP-4i, SGLT2i use was associated with a 38% lower probability of starting allopurinol, a common urate-lowering drug. Patients using SGLT2i had fewer prescriptions for NSAIDs, colchicine and high-dose glucocorticoids, and had fewer gout flares. They also had fewer prescriptions for diuretic medications, especially loop diuretics. These findings were consistent in different sensitivity analyses, including when comparing SGLT2i to GLP1-RA, and in a repeat analysis in an external dataset.
Q: What are the real-world implications, particularly for patients?
Our findings hold promise for those living with gout and type 2 diabetes (and for clinicians treating them). SGLT2i use could reduce their exposure to NSAIDs and glucocorticoids, which often have adverse effects, by lowering their use of gout-related medications. More broadly, SGLT2i use may streamline care for this patient population and reduce their medication burden.
Q: How might you build on these findings?
While undertaking this study, it was fascinating to learn more about polypharmacy (typically defined as regularly taking at least five medications), including how it's measured, its prevalence, the implications and potential ways it can be addressed. Polypharmacy hasn't been well studied in gout, so that's an avenue I'd like to pursue further in the future.
Authorship: In addition to McCormick, Mass General Brigham authors include Chio Yokose, Deborah Wexler, Sharan Rai, Greg Challener, Ran Abuhasira and Hyon Choi.
Paper cited: McCormick N., et al. "Gout-Related Medication Use After Initiating Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Gout and Type 2 Diabetes: Population-Based Target Trial Emulation Studies." Diabetes Care. DOI: 10.2337/dc25-1713
Funding: This work was supported by grants from the National Institutes of Health (NIH): (R00-AR080243) and (R01- AR065944).
Disclosures: McCormick, Burrack, Yokose, Lu, Rai, Challener, Aviña-Zubieta and Abuhasira have no disclosures. Wexler reports serving on Data Monitoring Committees for Novo Nordisk. In the last 36 months, McCoy has received unrelated research support from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH), National Institute on Aging (NIA) of the NIH, Patient Centered Outcomes Research Institute (PCORI), National Center for Advancing Translational Sciences (NCATS) and the American Diabetes Association. She also served as a consultant to EmmiEducate® (Wolters Kluwer) and the Yale-New Haven Health System's Center for Outcomes Research and Evaluation, and has received speaking honoraria and travel support from the American Diabetes Association. Choi reports research support from Horizon and LG Chem, and consulting fees from Ani, LG Chem, Horizon, Shanton and Protalix.
