Canagliflozin may reduce gout flare risk in people with type 2 diabetes
medwireNews: Treatment with the sodium-glucose cotransporter (SGLT)-2 inhibitor canagliflozin is associated with a reduction in serum urate concentration and gout flare risk among patients with type 2 diabetes, suggests a post-hoc analysis of the CANVAS Program trials published in The Lancet Rheumatology.
SGLT2 inhibitors “are the newest class of medication for type 2 diabetes and include canagliflozin, dapagliflozin, and empagliflozin, all of which have been approved by the US Food and Drug Administration and the European Medicines Agency,” explains Tuhina Neogi (Boston University School of Medicine, Massachusetts, USA) in an accompanying comment.
In their study, Bruce Neal (The George Institute for Global Health, Sydney, New South Wales, Australia) and colleagues analyzed data from 10,142 participants of the placebo-controlled CANVAS and CANVAS-Renal trials, which demonstrated the cardioprotective benefits of canagliflozin in patients with type 2 diabetes and a high risk for cardiovascular disease. At baseline, 5% of participants had a history of gout, and the average serum urate concentration was 348.9 μmol/L.
The investigators report that average serum urate levels “fell immediately” following treatment initiation in the canagliflozin group, decreasing to approximately 325 μmol/L at the 6-week follow-up, and remained lower among patients treated with canagliflozin versus placebo over a mean total follow-up of 3.6 years.
Average serum urate levels were 23.3 µmol/L lower in the canagliflozin than the placebo arm, equating to a 6.7% mean reduction.
Neal and colleagues note that this magnitude of reduction was “small” compared with that previously reported for canagliflozin (13% average reduction) and “substantially less” than that usually achieved with allopurinol or febuxostat (24–27%).
Nevertheless, they found that canagliflozin use had a strong negative association with gout flare risk. Rates of flare or initiation of gout therapy were 4.1 per 1000 person–years for canagliflozin-treated patients compared with 6.6 per 1000 person–years for those given placebo, giving a significant hazard ratio of 0.53.
“The large protective effect for gout observed with canagliflozin in the CANVAS Program, despite small reductions in serum urate concentration, suggests the possibility of protective mechanisms beyond urate lowering,” the team speculates.
Together, these findings “suggest a possible protective effect for gout from an agent used for the management of diabetes and, if confirmed in dedicated prospective studies, would provide a rationale for the selective use of canagliflozin among people with type 2 diabetes who have gout or are at high risk for gout,” write Neal and coinvestigators.
They add: “The data also raise the question as to whether canagliflozin might be an effective treatment for gout among patients without diabetes, which might be another future area for investigation.”
The commentator agrees that canagliflozin “appears to show potential for being a dual-benefit gout therapy, lowering serum urate and providing potential flare prophylaxis,” but cautions that “consideration of repurposing canagliflozin for gout management is not straightforward” due to potential adverse events including ketoacidosis, amputations, fractures, and acute kidney injury.
“Well conducted, appropriately powered phase 3 trials are warranted for careful benefit–risk evaluation and assessment of canagliflozin’s potential role as a urate-lowering, antiflare therapy,” concludes Neogi.
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