SGLT2 inhibitor canagliflozin reduces gout flares in type 2 diabetes: CANVAS Program

Delhi: Canagliflozin (Invokana) -- a medication used for the treatment of type 2 diabetes (T2D) -- lowered serum urate and reduced the risk of gout flare in T2D patients, finds a recent study published in The Lancet Rheumatology. The study was a post-hoc analysis of data from two large clinical trials -- CANVAS and CANVAS-Renal -- that assessed the cardiovascular and renal safety of canagliflozin compared with placebo in patients with type 2 diabetes.

Gout is a metabolic disorder characterized by increased uric acid in the blood and the deposition of amorphous urate crystals that cause a vigorous inflammatory reaction in the joints, kidneys, and soft tissues. It is characterized by sudden, severe attacks of pain, swelling, redness, and tenderness in the joints, often the joint at the base of the big toe. Gout symptoms may come and go, but there are ways to manage symptoms and prevent flares.

Management of gout remains poor, reflecting inadequate urate-lowering therapy doses, poor adherence, and insufficient therapeutic options for patients who are unable to take or have inadequate responses to available therapies. Patients with gout often have numerous comorbidities that require additional medications, adding complexity to their medication regimen.

Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that increases urinary glucose excretion and improves glycemic control, weight control, albuminaria and blood pressure in T2D patients. Treatment with canagliflozin reduces serum urate concentration in patients with type 2 diabetes with similar effects observed for other SGLT2 inhibitors. However, there is no information on whether SGLT2 inhibitors protect against gout.

The current CANVAS clinical trial program by Prof Bruce Neal, University of New South Wales, Sydney, Australia, and colleagues aimed to investigate the effect of canagliflozin compared with placebo on gout.

In the CANVAS Program, people with type 2 diabetes and an elevated risk of cardiovascular disease were randomly assigned to receive either canagliflozin (100 or 300 mg) or placebo.

• Mean follow-up was 3·6 years (SD 2·0) and mean serum urate concentration was −23·3 μmol/L lower in participants treated with canagliflozin than in those who received placebo, equating to a 6·7% reduction in serum urate.


• During follow-up, 80 individuals reported an episode of gout flare and 147 commenced a drug for gout.


• The occurrence of gout flare or the need for treatment for gout was lower in participants treated with canagliflozin than in those who received a placebo (HR 0·53).


• The proportional reduction for gout flare adverse events (2·0 patients with an event per 1000 patient-years in the canagliflozin group vs 2·6 patients with an event per 1000 patient-years in the placebo group; 0·64) was similar in size to that for commencement of a drug for gout (3·3 vs 5·4 patients with an event per 1000 patient-years; 0·52) and hyperuricemia (1·8 vs 2·5 patients with an event per 1000 patient-years; 0·59).

Read Also: Canagliflozin not only lowers blood sugar but also reduces kidney failure risk in Diabetes

"This agent (canagliflozin) appears to show potential for being a dual-benefit gout therapy, lowering serum urate and providing potential flare prophylaxis and thereby potentially reducing the need for separate flare prophylaxis with agents that are often contraindicated or poorly tolerated in patients with gout," Tuhina Neogi, Boston University School of Medicine, Boston, MA, USA, wrote in an accompanying comment.

DOI: https://doi.org/10.1016/S2665-9913(19)30078-5