Gout’s Metabolic Risk Factors
Dr. Schlesinger
The final speaker was Naomi Schlesinger, MD, a professor of medicine, endowed chair and chief of the Division of Rheumatology at the Spencer Fox Eccles School of Medicine at the University of Utah, who talked about the treatment of gout and its metabolic risk factors. Dr. Schlesinger noted that colchicine has anti-inflammatory effects that are mediated by inhibition of microtubule polymerization and suppression of neutrophil and inflammasome activity. The use of colchicine has been shown to reduce major adverse cardiovascular events in large randomized trials of patients with coronary artery disease. The COLCOT and LoDoCo2 trials demonstrated that low-dose colchicine (0.5 mg daily) reduced the risk of MI, stroke, coronary revascularization and cardiovascular death by 23–31% compared with placebo, with benefits additive to standard therapies such as statins and antiplatelet agents.14-15 In 2023, the FDA approved low-dose colchicine for secondary prevention in adults with established atherosclerotic disease or multiple cardiovascular risk factors.
A very hot topic of late has been the role of sodium–glucose cotransporter 2 (SGLT2) inhibitors in the treatment of gout. Mechanistically, SGLT2 inhibitors lower serum urate by promoting glycosuria, which competes with urate for reabsorption in the proximal tubule and thus enhances urinary urate excretion. Additional anti-inflammatory effects, such as suppression of IL-1β and downregulation of xanthine oxidase via SIRT-1 signaling, may further contribute to reduced gout flares and cardiovascular risk. Meta-analyses of randomized controlled trials confirm that SGLT2 inhibitors significantly reduce the risk of composite gout outcomes, with dapagliflozin and canagliflozin showing particularly strong urate-lowering effects.16-17 These benefits appear independent of baseline serum urate and are not limited to patients with diabetes, suggesting broader applicability in populations at risk for gout. Thus, SGLT2 inhibitors may offer dual benefit for patients with coexisting diabetes and gout, though the potential benefit for treating gout alone with these medications is less well established and should be considered adjunctive rather than primary therapy.
Even though gout is an old disease, the concepts covered by the speakers were timely and relevant to the clinical audience. Those in attendance looked into the crystal ball of gout and can see a future in which the disease continues to receive the research attention it deserves, leading to improvements in patient care.
Jason Liebowitz, MD, FACR, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.
