HMN 2026: How Use of glucose-lowering SGLT2i drugs may help patients with gout and diabetes take fewer medications

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.

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).

A team led by Natalie McCormick, Ph.D., of the Rheumatology and Allergy Clinical Epidemiology Research (RACER) Center within the Division of Rheumatology in the Mass General Brigham Department of Medicine, 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?

According to the researchers, 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.

The team emulated a randomized clinical trial using large, population-based datasets. The findings were published in Diabetes Care, in a paper titled “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.”

The study involved 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.

The researchers used statistical techniques to balance baseline characteristics between treatment groups (for example, demographics, number of recent gout flares, etc.), thus mimicking randomization. The team 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.

Key findings

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.

Real-world implications

The 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.

While undertaking this study, the authors say, 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 McCormick would like to pursue further in the future.

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