SGLT2 Inhibitors Associated With Increased Risk for Genital Infections

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SGLT2 inhibitors increase the availability of glucose in the genitourinary tract; in clinical trial data, their use has been associated with a 3- to 5-fold increase in genital infections.
SGLT2 inhibitors increase the availability of glucose in the genitourinary tract; in clinical trial data, their use has been associated with a 3- to 5-fold increase in genital infections.

Compared with other classes of antidiabetic drugs, sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with an approximately 3-fold higher risk of developing genital infections, according to findings published in Diabetes, Obesity, and Metabolism.

SGLT2 inhibitors are a newer class of antidiabetic medications that increase the availability of glucose in the genitourinary tract. Because of this, clinical trial data have linked SGLT2 inhibitor use to a 3- to 5-fold increase in genital infections, which can predispose patients to poor therapy adherence. The magnitude and consistency of this risk across all subgroups, however, has not been well defined in research. The investigators in this study used 2 US commercial claims databases to compare patients with type 2 diabetes who were treated with SGLT2 inhibitors vs those receiving dipeptidyl peptidase-4 (DPP-4) inhibitors for risk for genital infections, including risk associated with within-individual SGLT2 inhibitors and duration of therapy. The primary outcome was an episode of genital infections, defined as a composite of genital candidal infections, vaginitis, or vulvovaginitis in women, or genital candidal infections, balanitis, balanoposthitis, phimosis, or paraphimosis in men.

In the propensity score-matched cohorts composed of 129,994 women and 156,074 men, the adjusted hazard ratio and excess risk per 1000 person-years for women taking SGLT2 inhibitors compared with DPP-4 inhibitors was 2.80 (95% CI, 2.63-2.99) and 87.4 (95% CI, 79.1-96.7), respectively. For men taking SGLT2 inhibitors compared with DPP-4 inhibitors, the ratios were similar, at 2.66 (95% CI, 2.30-3.08) and 11.9 (95% CI, 9.4-15.0). Similar findings were observed for comparisons of SGLT2 inhibitors with glucagon-like peptide-1 agonists, and the risk was greater in the subgroup of patients aged ≥60 years, with hazard ratios of 4.45 (95% CI, 3.83-5.17) in women and 3.30 (95% CI, 2.56-4.25) in men.

The analysis of individual SGLT2 inhibitors found that canagliflozin was associated with a slightly higher risk for genital infections. However, the researchers noted that the heterogeneity in characteristics of clinical trials in the study made it difficult to estimate risk for individual agents.

Further limitations of the study included systematic exclusion of cases of genital infections with mild underlying symptomology not associated with a medical encounter and potential confounders such as circumcision status or behavioral risks, although the calculated effect sizes were unlikely to be fully explained by these factors.

"The risk [for] genital infections should be evaluated against the glycemic and cardiovascular benefits when prescribing these agents," the researchers concluded.

Reference

Dave CV, Schneeweiss S, Patorno E. Comparative risk of genital infections associated with SGLT2 inhibitors: A real-world retrospective cohort study [published online September 12, 2018]. Diabetes Obes Metab. doi:10.1111/dom.13531

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