SGLT2 inhibitors score big, this time in gout

Patients initiated on gliflozins or flozins – also called sodium-glucose co-transporter 2 (SGLT2) inhibitors – for type 2 diabetes (T2D) who were previously on metformin had reductions in the incidents of gout of up to 60 percent compared with other second-line agents in a recent study.

Hazard ratios for gout with SGLT2 inhibitors were 0.54 vs dipeptidyl peptidase-4 (DPP4) inhibitors, 0.39 vs glucagon-like peptide 1 (GLP1) analogues, and 0.61 vs sulfonylurea agents. “These results were all highly significant,” said study author Dr Natalie McCormick from the Massachusetts General Hospital in Boston, Massachusetts, US. “The same patterns were seen even in those subgroups stratified by age, sex, and co-treatment with diuretics.”

Studies support the urate-lowering effect of SGLT2 inhibitors

The findings did not come as a surprise as SGLT2 inhibitors prevent glucose reabsorption and have been shown to lower serum urate levels in some studies, she added. [Expert Opin Investig Drugs 2010;19:1581-1589; Ann Intern Med 2020;172:186-194]

Excessive uric acid precipitates into crystalline urate crystals, which manifest as acute episodes of painful arthritis and form gout, McCormick explained. [Lancet Rheumatol 2021;3:e58–70]

“Interestingly, we have studies showing that patients with T2D on SGLT2 inhibitors had a reduced gout risk,” said McCormick. [Diabetes Obes Metab 2022;24:135-141]

This, and the current findings, expand the potential utility of SGLT2 inhibitors beyond glucose-lowering and cardio-renal protection.

She clarified that although the disease mechanisms in gout and T2D are not directly related, both conditions share a few risk factors, such that the likelihood of having one is markedly higher if an individual also has the other condition. “However, the extent to which metformin therapy might have confounded the data was not clear, as the use of the drug was not systematically tracked.”

SGLT2 inhibitors vs other glucose-lowering agents

McCormick and her team analysed data from British Columbia’s universal healthcare system which recorded all prescription drugs dispensed, on top of clinical and utilization data.

Included in the analysis were patients with ICD-9/10 codes for diabetes who started second-line medications (SGLT2 or DPP4 inhibitors, GLP1 analogues, or sulfonylureas) from 2014 through 2021 among metformin users. [EULAR 2023, abstract OP0258]

Primary endpoints (indicating gout onset) include emergency department visits or hospital admissions for gout or a gout-coded drug prescription.

Mycotic genital infections and osteoarthritis diagnoses were also assessed, with higher rates of mycotic genital infections expected in those receiving SGLT2 inhibitors compared with the other medication classes.

Each group was matched with the SGLT2 inhibitor users based on age, sex, disease duration, rates of major diabetic complications, and previous healthcare utilization.

In the group with DPP-4 inhibitors as the comparator, the mean age was 61 years, 58 percent were men, with a diabetes duration of 10 years. Almost half of the cohort had a major complication such as retinopathy.

Overall, 52,000 patients were treated with SGLT2 inhibitors, 13,000 received DPP4 inhibitors, 5,000 had GLP1 analogues, and 42,000 were treated with sulfonylureas.

McCormick said there was consistency of results across the subgroups and because the data were population-based, generalizability was feasible.

The study was supported by Arthritis Research Canada.