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30-04-2024 | Gout | Editor's Choice | News

SGLT2 inhibitors show gout prevention benefit over sulfonylureas in type 2 diabetes

Author: Matthew Williams

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medwireNews: Treating adults with type 2 diabetes with sodium-glucose cotransporter (SGLT)2 inhibitors instead of sulfonylureas reduces the risk for incident gout and gout flares in addition to offering cardiovascular benefits, finds a study published in JAMA Internal Medicine.

While earlier studies with SGLT2 inhibitors have revealed an association for gout protection compared with dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 receptor agonists, there is a lack of comparative evidence with sulfonylureas, “the second most widely used class of glucose-lowering medication after metformin,” explain Hyon Choi (Harvard Medical School, Boston, Massachusetts, USA) and colleagues.

The researchers analyzed data from nationwide Canadian administrative databases on emergency department and outpatient medical visits, hospital discharges, and dispensed prescriptions records, for people with type 2 diabetes who were already receiving metformin and started treatment with SGLT2 inhibitors, primarily empagliflozin, or sulfonylureas between 2014 and 2022.

Their propensity score-matched comparative effectiveness study, which used a target trial emulation framework, included 34,604 people with type 2 diabetes who did not have gout at baseline (mean age 60 years; 60% men).

Over a mean follow-up of 1.38 years, 105 (0.61%) of the 17,302 patients in the SGLT2 inhibitor group developed incident gout, compared with 159 (0.92%) of the 17,302 patients in the sulfonylurea group, equating to a significant 38% reduced risk after taking into account confounding factors such as sociodemographic factors, diabetes duration and complications, comorbidities, gout risk factors, and relevant medications. The respective rates per 1000 person–years were 4.27 versus 6.91, with a rate difference of 2.64.

Moreover, SGLT2 inhibitor use was associated with 66% fewer incident gout events that resulted in emergency room visits or hospitalization.

The observed benefit with SGLT2 inhibition persisted irrespective of sex, age, and baseline diuretic use, the team reports, although the rate difference was greater among patients considered at increased risk for gout, including men, older patients, and those using diuretics at baseline.

To assess the comparative effectiveness for reducing recurrent gout flares, the investigators also used propensity score matching to compare SGLT2 inhibitor and sulfonylurea use in 5388 patients (mean age 64 years at index date; 76% men) who had gout at baseline. They found that the risk for recurrent flares was a significant 33% lower for the 2694 patients in the SGLT2 inhibitor group than the 2694 patients in the sulfonylurea group, corresponding to 21 fewer flares per 1000 person–years, at 45.0 versus 66.0, respectively.

Choi et al explain that previous meta-analyses have shown that SGLT2 inhibitors reduce serum urate levels, with the primary mechanism thought to be via increased glycosuria. However, the known benefits of SGLT2 inhibitors for reducing cardiometabolic outcomes may also play a part, they suggest.

Indeed, the study’s secondary outcome of major adverse cardiovascular events was less common among patients in the SGLT2 inhibitor group than the sulfonylurea group, with 456 events compared with 503 in the sulfonylurea group over a mean follow-up of 1.4 and 1.3 years, respectively. This corresponded to a significant 13% reduced risk for patients taking SGLT2 inhibitors and an adjusted rate difference of 3.6 per 1000 person–years, at 18.9 versus 22.4, respectively.

While the investigators did not have access to laboratory measures such as glycated hemoglobin, uric acid, or kidney function tests nor environmental and lifestyle exposures, they say it is unlikely that these factors would confound the choice between the two treatments with respect to gout risk, since neither was “approved or clinically considered for gout risk or care in practice during the study period.”

They conclude: “The gout and cardiovascular benefits associated with SGLT2 [inhibitors] in these target trial emulations may guide selection of glucose-lowering therapy in patients with [type 2 diabetes] who are at risk for (or already have) gout needing a second-line agent after metformin.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Intern Med 2024; doi:10.1001/jamainternmed.2024.0376

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