Best diabetes drug for gout outcomes

3 minute read

SGLT2 inhibitors are better at reducing gout flares and heart attack in patients with diabetes and gout than DPP-4 inhibitors, according to a large observational study.

A large study has found that people with type 2 diabetes and gout had better gout and cardiovascular outcomes when treated with SGLT2 inhibitors compared with DPP-4 inhibitors.

Type 2 diabetes is among the many cardiometabolic comorbidities accompanying gout, which also include metabolic syndrome, chronic kidney disease and cardiovascular disease.

“Thus, gout care interventions that can simultaneously address both gout flares and cardiometabolic risk would be ideal,” the authors wrote in the Annals of Internal Medicine.

SGLT2 inhibitors, which have pleiotropic cardiometabolic renal benefits and reduce serum urate levels in people with and without type 2 diabetes, are a potential candidate.

Researchers analysed a database of British Columbian residents, which identified over 15,000 patients with both gout and type 2 diabetes who initiated either SGLT2 inhibitors or DPP-4 inhibitors.

They found that patients on SGLT2 inhibitors had a 34% lower rate of recurrent gout flare and a 48% lower rate of flares requiring ED visit or hospitalisation than those on DPP4 inhibitors over the following year or two. Myocardial infarctions were 31% less likely among SGLT2 inhibitor patients, though there no significant difference for stroke between groups.

The most common prescriptions were empagliflozin (SGLT2i) and linagliptin (DPP-4i).

“The absolute risk reduction tended to be larger among persons not using urate-lowering therapy at baseline and was substantially greater among patients with greater gout intensity,” the authors wrote.

However, the authors noted, being less potent urate-lowering agents, SGLT2 inhibitors could not replace current prototypic urate-lowering agents needed by many patients with gout.

“If a patient has relatively mild hyperuricemia, SGLT2i treatment alone could sufficiently lower their serum urate to the target level of <0.36mmol/L without urate-lowering therapy (ULT) such as allopurinol or febuxostat,” rheumatology professor and co-author Hyon Choi of Harvard Medical School told Rheumatology Republic.

If SGLT2 inhibitors were indicated for the patient’s comorbidities, then this option would be killing “two birds with one stone”, Professor Choi said.

“However, if patients have more substantial hyperuricemia or features of advanced cases such as subcutaneous tophi, SGLT2i is unlikely to replace conventional ULT, but could be used as an adjunct therapy to help lower ULT dose requirement, with additional cardiometabolic benefits,” said Professor Choi.

The researchers also compared the results for SGLT2 inhibitors with patients taking GLP1-RAs, which are also known to reduce serum urate levels. They found that SGLT2 inhibitors were associated with around half the rate of ED visits and hospitalisations as GLP1-RAs.

The main limitation of the study was that only gout flares receiving medical attention were captured. Data was also limited by the lack of measures such as serum urate and HbA1c levels to indicate disease severity.

“This general population-based study showed that SGLT2i initiation was associated with lower risk for recurrent gout flares (the cornerstone of clinical gout care) and gout-primary ED visits and hospitalisations, along with myocardial infarction, compared with DPP-4is in patients with prevalent gout and type 2 diabetes,” concluded the authors.

“Given the pleiotropic cardiometabolic benefits associated with SGLT2is among patients with type 2 diabetes, this class of medications may be a particularly attractive addition to our current urate-lowering therapies to simultaneously address the high burden of gout and cardiometabolic sequelae.”

Annals of Internal Medicine 2023, online 25 July

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