SGLT2 inhibitors ‘substantially’ reduce gout risk in patients with type 2 diabetes
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SAN DIEGO — Sodium-glucose cotransporter-2 inhibition may reduce the risk for gout by as much as 40% to 60% among certain patients with type 2 diabetes treated with metformin, according to data presented at ACR Convergence 2023.
“Our objective was to emulate recent clinical trials and compare incident gout risk among metformin-treated patients with type 2 diabetes initiating SGLT2 inhibitors vs. other second-line treatments,” Natalie McCormick, MD, of Massachusetts General Hospital, told attendees.
SGLT2 inhibitors may reduce cardiovascular and all-cause mortality risk, along with lowering risk for heart failure and chronic kidney disease progression, she added. In addition, clinical trials of SGLT2 inhibition have shown reductions in serum urate levels.
McCormick and colleagues conducted a new-user, active comparator, population-based cohort study using administrative health data for nearly all residents of British Columbia, Canada, from Jan 2014 to June 2022. The analysis included all dispensed prescriptions regardless of funder, according to the researchers. The comparator drugs included dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP1-RA) or sulfonylureas. Incident gout served as the primary endpoint.
The comparison of SGLT2 inhibitors vs. DPP-4 inhibition included 27,791 patients. This group was 58% men, with a mean age of 61 years. The comparison of SGLT2 inhibitors vs. GLP1-RA included 19,875 patients, of whom 44% male, with a mean age of 57 years. Lastly, the comparison of SGLT2 inhibition vs. sulfonylurea featured 71,625 patients, of whom 60% were men, with a mean age of 59 years. Baseline characteristics were balanced across treatment groups.
“All the treatment groups were mutually exclusive,” McCormick said. “Patients were followed from the time of first dispensing of medication to the end of study, deregistration, discontinuation, initiation of a comparator medication or death.”
According to the researchers, SGLT2 inhibition reduced incident gout risk (weighted HR = 0.54; 95% CI, 0.39-0.74) compared with DPP-4i initiation. In addition, similar reductions in gout risk were observed in the comparisons between SGLT2 inhibition and GLP1-RA (weighted HR = 0.39; 95% CI, 0.24-0.62) and SGLT2 inhibitors vs. sulfonylureas (weighted HR = 0.61; 95% CI, 0.46-0.80). Age, sex and baseline diuretic use failed to impact these outcomes, the researchers wrote.
“Our findings were consistent across subgroups,” McCormick said.
Meanwhile, safety data showed that initiation of SGLT2 inhibitors was associated with an increased risk for genital infection compared with the other interventions. No difference in osteoarthritis risk was reported across treatment groups.
“Along with their known cardiovascular and survival benefits, SGLT2 inhibitors could reduce risk for incident gout substantially for patients with type 2 diabetes needing a second-line agent after metformin,” McCormick said. “Given that gout now affects 12 million U.S. adults with high cardiometabolic comorbidity burden and persistent premature mortality, this agent could help address the whole disease burden of gout.”
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N. Lawrence Edwards, MD, MACP, MACR
One of the very important abstracts at this year’s American College of Rheumatology Convergence was this study by Natalie McCormick, MD, and her collaborators from Massachusetts General Hospital and Vancouver. Multiple previous studies have shown a clear association between the glycosuria induced by SGLT2 inhibitors and enhanced urinary excretion of uric acid, and a lower incidence of gout. However, this active comparative study, compares SGLT2 inhibitors taken along with metformin to the other adjunctive therapies added to metformin, concerning the development of gout.
The SGLT2 inhibitor with metformin outperformed the other two combinations with weighted HRs between 0.61 and 0.39.
Gout remains a poorly treated disease. This is generally attributed to patients’ non-adherence to therapy or the physician’s inadequate dosing of urate-lowering therapy. Many also blame the multiple comorbidities associated with gout that distract the treating physician away from focusing on hyperuricemia and gout. Two of these comorbidities are hypertension and type 2 diabetes, which occur in 74% and 26% of gout patients, respectively, according to NHANES 2007-2008 data.
We know that losartan helps lower serum urate while other antihypertensive therapies, including other angiotensin II receptor blockers, have the opposite effect. When we relay this information to the primary care physician, we are helping to focus more attention to gout. Similarly, we now have a new standard treatment that lowers serum urate and decreases the development of gout while effectively treating type 2 diabetes, a disease the primary care physicians are more likely to be focused on.
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McCormick N. Abstract 742. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego (hybrid meeting).
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