The use of SGLT2 inhibitors (SGLT2i) was associated with fewer gout flares and reduced use of gout medication among adults with both gout and type 2 diabetes (T2D), according to results of a new study.

“In addition to the acutely painful joint flares, gout is associated with a high burden of cardiovascular-kidney-metabolic [CKM] comorbidities, including T2D” which afflicts “approximately 25% of individuals with gout,” lead author Natalie McCormick, PhD, an epidemiologist and instructor in medicine at Massachusetts General Hospital, Boston told Medscape Medical News.

“Conventional urate-lowering therapies are recommended for gout flare prevention, but don’t help with the CKM comorbidities, thus necessitating different medication classes for gout and comorbidity care,” she added. “This makes treatment decisions more complex, while increasing pill burden for patients and the potential for drug-drug interactions.”

Since receiving FDA-approval in 2013 as glucose-lowering agents for individuals with T2D, SGLT2i have shown additional benefits in areas including cardiovascular, metabolic, and kidney health.

They have also shown an ability to reduce serum urate levels, and, consequently, gout flares, noted McCormick and colleagues in their study, recently published in Diabetes Care.

However, the specific impact of SGLT2i on reducing the need for additional gout medications in patients with both gout and T2D has not been well examined, the researchers wrote.

Impact on Urate-Lowering Therapy

For the current study, the researchers identified 18,984 adults with gout and T2D with no baseline use of urate-lowering therapy and a mean age of 66 years. They used hazard models and regressions to model a randomization of patients to SGLT2i or DPP-4 inhibitors, with GLP-1 receptor agonists (GLP-1 RAs) as an alternative comparator. The primary outcome was initial dispensing of allopurinol as a urate-lowering therapy.

Overall, the use of SGLT2i was associated with a 38% decreased use of allopurinol, with a hazard ratio (HR) of 0.62 (95% CI, 0.52-0.73). SGLT2i use also was associated with reduced rates of recurrent gout flares (rate ratio [RR], 0.65; 95% CI, 0.60-0.72).

Associations between SLGT2i use and reduced use of gout medication were stronger among individuals who were using diuretics at baseline (P for interaction =.03) and when comparing SGLT2i with GLP-1 RAs, accounting for serum urate and BMI. In addition, the use of SGLT2i was associated with lower rates of dispensing of high-dose glucocorticoids, indomethacin, and colchicine, with RRs of 0.78 (95% CI, 0.74-0.83), 0.85 (95% CI, 0.80-0.92), and 0.87 (95% CI, 0.83-0.92), respectively.

Impact on Rates of Dispensing Diuretics

The most surprising findings from the study were those on diuretic medication use, McCormick told Medscape Medical News.

Rates of dispensing diuretics were lower in patients using SGLT2i compared with both DPP-4 inhibitor and GLP-1 RAs, with RRs of 0.87 (95% CI, 0.85-0.89), and 0.82 (95% CI, 0.80-0.85), respectively, with a notable RR of 0.58 (95% CI, 0.56-0.60) for loop diuretics alone compared with DPP-4 inhibitor.

These results align with findings from randomized, controlled trials of SGLT2i in patients with heart failure, but the researchers did not necessarily expect the same in the current study population, McCormick noted.

When choosing a glucose-lowering agent, consider that patients with T2D and gout may particularly benefit from an SGLT2i for the pleiotropic glucose-lowering and gout benefits, she said. “For patients with a larger urate burden, SGLT2is could be used in combination with conventional urate-lowering therapy,” she added.

The study was limited by the inclusion only of patients with gout and concomitant T2D, and future work should examine the implications for urate-lowering therapy use in patients with other indications for SGLT2i, as numbers accrue, McCormick added.

Data Support Efficient and Effective Care

“Gout patients with diabetes are certainly exposed to harmful agents, such as NSAIDs [nonsteroidal anti-inflammatory drugs] and glucocorticoids,” said Angelo Gaffo, MD, MsPH, professor of medicine at the Heersink School of Medicine at The University of Alabama at Birmingham. “Improving clinical outcomes is urgent and imperative.”

In addition, the burden of gout is rapidly increasing, currently estimated at 5% of the total US population, and the burden is likely greater among individuals with diabetes, said Gaffo, who was not involved in the current study.

The new study results build on prior findings of SGLT2i as useful agents for lowering serum urate and, independently, preventing flares in patients with gout, Gaffo told Medscape Medical News.

“Most of these studies have been done in the context of concurrent diabetes, but some studies have also found these benefits even in individuals without diabetes,” he said.

For patients with the common comorbidities of gout and T2D, “SGLT2is might be the agent of choice to improve gout clinical outcomes and related comorbidities as gout is associated with chronic kidney disease and adverse cardiovascular outcomes through inflammatory pathways,” he added.

Limitations of the current study include the potential for unmeasured confounding, despite careful adjustments, Gaffo noted, therefore, “the natural next step would be to design an interventional study to confirm that patients with gout who receive SGLT2is have improved clinical outcomes,” specifically reduced gout flares.

This study was supported by the National Institutes of Health and by THC-135235 (Preventing Complications From Inflammatory Skin, Joint and Bowel Conditions), a team grant funded by the Canadian Institutes of Health Research.

McCormick reported receiving support through a Career Development Award from the National Institutes of Health but disclosed having no financial conflicts of interest.

Gaffo disclosed consulting for SOBI, PK-Med, Protalix, and Scilex.