Women at significant risk for urinary, genital infections while using SGLT2i
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SAN DIEGO — Women with autoimmune and rheumatic conditions are at a significant risk for adverse events during treatment with sodium glucose cotransporter 2 inhibitors, according to data presented at ACR Convergence 2023.
“In recent years, sodium glucose cotransporter 2 (SGLT2) inhibitors have emerged as a novel treatment for myriad indications beyond diabetes mellitus, including cardiovascular disease, kidney disease, heart failure, obesity and atherosclerosis prevention,” Emily G. Oakes, BA, of Brigham and Women’s Hospital, in Boston, told Healio. “Alongside the demonstrated effectiveness of these medications in clinical trials, adverse events associated with SGLT2-inhibitor use, such as infections, urinary and genital infections in particular, are also well-documented.”
Due to the theoretical infection risk, patients with autoimmune rheumatic diseases have not been included in SGLT2-inhibitor clinical trials, she added.
“The risk for adverse events associated with SGLT2 inhibitors among patients with autoimmune rheumatic diseases is not well-established,” Oakes said.
To compare adverse events associated with SGLT2-inhibitor use in patients with and without autoimmune rheumatic diseases, Oakes and colleagues analyzed patients seen throughout the Mass General Brigham hospital network. Eligible patients included those with two or more diagnostic codes associated with autoimmune rheumatic diseases who had been prescribed either dapagliflozin (Farxiga, AstraZeneca), canagliflozin (Invokana, Janssen), or empagliflozin (Jardiance, Boehringer Ingelheim) between Jan. 1, 2016, and Dec. 10, 2021.
Each patient with autoimmune rheumatic diseases was matched based on age, sex and race to an individual without an autoimmune disease who had been prescribed the same SGLT2 inhibitor. From 519 participants in each group, the final analysis included 466 in the patient group and 427 controls. The mean age for both cohorts was 64 years, with women comprising 61% of the study population. Participants in the patient group were more likely to be past smokers.
The most medication was empagliflozin, accounting to 78% of prescriptions. Patients in the autoimmune group demonstrated a baseline A1c level of 8.08 mg/dL, compared with 8.10 mg/dL among controls.
The researchers identified 12 categories of adverse events and discontinuations. The most common were yeast infections, which occurred in 9.9% of the patient cohort and in 6.1% of controls (P = .04), they wrote. Myalgias and weakness were also more common in the patient group, 3.4% vs. 0.9% (P = .01).
Participants in the patient group reported significantly shorter duration of SGLT2-inhibitor use — 8.7 months vs. 12.6 months (P < .0001) — and time to adverse event — 0.62 years vs. 0.96 years (P < .0001).
According to the researchers, the multivariable analysis demonstrated a significant increased risk for adverse events in the patient group, compared with controls (HR = 1.74; 95% CI, 1.33-2.29). This trend persisted after adjusting for glucocorticoid and use of disease-modifying antirheumatic drugs (HR = 1.80; 95% CI, 1.34-2.4).
“We identified a significant, greater than 75% overall higher adverse event risk in patients with autoimmune rheumatic diseases relative to comparators without these diseases,” Oakes said, adding that these primarily included genitourinary adverse events such as yeast infections and urinary tract infections.
There was also a separation between the two groups in terms of event-free survival over time, according to Kaplan Meier analysis (all log-rank P < .001).
Meanwhile, women were significantly more likely than men to experience adverse events (P < .00001), according to the researchers. Moreover, women in the patient group were more than twice as likely as women without an autoimmune rheumatic condition to experience an adverse event, even after adjusting for glucocorticoid and immunosuppressant use (HR = 2.05; 95% CI, 1.47-2.85).
“In our sex-stratified analyses, females in both groups were most affected,” Oakes said. “Female patients with rheumatic disease demonstrated 4.5-times greater incidence of adverse events compared to the lowest risk group — males without autoimmune rheumatic diseases — and nearly doubled risk compared to the next highest risk group — females without autoimmune rheumatic diseases. Males with rheumatic disease, however, did not appear to be at a significantly increased risk compared with men without.”
The findings may point the direction of future study, according to Oakes.
“We believe that these findings warrant further testing of safety and efficacy of SGLT2 inhibitors among patients with rheumatic disease to provide a cost-benefit analysis of SGLT2-inhibitor utilization in this population,” she said.
“Providers may consider infection and adverse event risk more heavily when prescribing SGLT2 inhibitors to patients with comorbid rheumatic disease, in particular women who appear to have the greater risk of adverse event,” Oakes added. “Rheumatologists now should be aware of potentially increased infection risks, in particular increased risk for urinary and genital infections for women, inform their patients, and beware of the potential for infections after prescription.”
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Oakes EG, et al. Abstract #0741 Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego (hybrid meeting).
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