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SAN DIEGO -- Rates of certain infections and other adverse effects were substantially higher in patients receiving sodium-glucose cotransporter-2 (SGLT-2) inhibitors when they also had rheumatoid arthritis or other systemic autoimmune rheumatic diseases (SARDs), a researcher reported here.

Women were particularly affected, according to Emily Oakes, BA, of Brigham & Women's Hospital in Boston, speaking at the American College of Rheumatology's annual meeting. A fully adjusted model indicated that risk of any adverse event was doubled in female SARD patients taking SGLT-2 inhibitors (HR 2.05, 95% CI 1.47-2.85) compared with non-SARD patients on these medications.

Yeast infections and myalgia and muscle weakness were the adverse effects increased the most with SGLT-2 inhibitors in SARD patients, Oakes noted. In her analysis of some 900 patients prescribed these drugs, 9.9% of SARD patients suffered yeast infections versus 6.1% in the absence of SARD (P=0.04). Muscular symptoms were reported in 3.4% of those with SARDs as opposed to 0.9% in those without (P=0.01).

SGLT-2 inhibitors, also known as gliflozins, are prescribed primarily for type 2 diabetes and also for heart failure patients at high risk for acute cardiovascular events. These drugs force the kidneys to excrete glucose from the blood. Because this mechanism increases the sugar content of urine, the urinary tract and, in women, the vaginal area become more hospitable to bacteria and fungi that feed on sugars. (Jardiance) warn of increased risk for urinary tract and vaginal infections.

For SARD patients, Oakes explained, the problem could be magnified insofar as these individuals typically take medications that suppress immune function to some degree. Her group sought to examine this possibility through records of patients prescribed SGLT-2 inhibitors in the Mass General Brigham hospital system.

The researchers identified 466 SARD patients who initiated SGLT-2 inhibitor treatment during 2016-2021. They then looked for non-SARD patients also starting on these medications who matched the SARD group as closely as possible by age, sex, and specific gliflozin drug, ending with 427 to serve as controls. Comparisons were adjusted for other factors including body mass index, race-ethnicity, smoking status, concomitant anti-rheumatic drugs, year of gliflozin initiation, and the indication for gliflozin use.

Patients' mean age was 64 and about 60% were women. Just over two-thirds were white, and some 40% had a smoking history. BMI values averaged about 33. Three-quarters had taken empagliflozin.

Roughly half of the SARD patients had rheumatoid arthritis, and almost one-quarter had psoriatic arthritis. Other SARDs including lupus, Sjogren's syndrome, systemic sclerosis, and inflammatory myositis were also represented. Some 37% of the SARD group were using corticosteroids, 17% were on hydroxychloroquine, 26% took targeted anti-rheumatic drugs, and 28% were on traditional immunosuppressants.

Individual adverse events were relatively infrequent; yeast infections were the most common and these were seen in less than 10% of the overall population. As a result, the study was somewhat underpowered to address specific types of adverse events. Only for yeast infections and muscular pain or weakness did the between-group differences meet the threshold for statistical significance. But many other event types showed trends toward increased risk in SARD patients: urinary tract infections (5.6% vs 3.3%), non-infectious urinary symptoms (1.5% vs 0.7%), and vaginal itching or irritation (3.0% vs 1.2%). Rates of diabetic ketoacidosis, perhaps the most serious risk with SGLT-2 inhibitors, were identical in SARD versus non-SARD patients.

The data suggested that women were more at risk than men for increased adverse effects with SARDs. For events of any type, male SARD patients faced a nonsignificant risk increase of just 37% (HR 1.37, 95% CI 0.69-2.70), although this too could reflect the relatively small number of people involved, and the fact that men aren't subject to certain adverse effects linked to SGLT-2 inhibitors (most notably, vaginal yeast infections).

Limitations to the analysis included the relatively small number of patients and the reliance on administrative data. As well, the small numbers precluded examining whether particular types of SARD treatment were more likely than others to show increases in adverse events with gliflozin use. Oakes also pointed out a potential for confounding by unmeasured factors, such as use of medications other than those prescribed for SARDs.

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