Why does Jardiance (Empagliflozin) cause candidiasis, but not bacterial infections?

From the Guidelines

Jardiance (empagliflozin) primarily causes candidiasis (yeast infections) rather than bacterial infections due to its mechanism of action as an SGLT2 inhibitor, which increases glucose excretion in the urine and creates a sugar-rich environment that favors the growth of Candida fungi. As an SGLT2 inhibitor, Jardiance increases glucose excretion in the urine, creating a sugar-rich environment in the genital area that specifically favors the growth of Candida fungi 1. Yeast organisms thrive on glucose as a nutrient source, while most pathogenic bacteria don't depend on glucose to the same extent. The increased urinary glucose creates an ideal breeding ground for Candida species, disrupting the normal microbial balance. Additionally, the slightly acidic pH changes in the genital area resulting from Jardiance use further promote fungal growth while many bacteria prefer different pH conditions.

Some key points to consider:

• The risk of genital mycotic infections is higher for women than men, with a meta-analysis of clinical trials reporting that genital mycotic infections occurred in 6% of participants assigned to an SGLT2i, compared with 1% of those assigned to placebo 1.
• Daily hygienic measures may lessen this risk, and most genital mycotic infections are easily treated, but severe cases of Fournier gangrene have been reported 1.
• Good hygiene practices, keeping the genital area dry, and prompt treatment of any yeast infections are important preventive measures for patients using this medication.
• Treatment of vulvovaginal candidiasis should not differ on the basis of human immunodeficiency virus (HIV) infection status; identical response rates are anticipated for HIV-positive and HIV-negative women 1.
• Uncomplicated infection can be effectively treated with either single-dose fluconazole or short-course fluconazole for 3 days, both of which achieve >90% response 1.

Overall, the increased risk of candidiasis associated with Jardiance use can be managed with proper hygiene practices and prompt treatment of any yeast infections, and patients should be counseled on genital hygiene to reduce this risk 1.

From the FDA Drug Label

The adverse reactions were not present at baseline, occurred more commonly on JARDIANCE than on placebo and occurred in greater than or equal to 2% of patients treated with JARDIANCE 10 mg or JARDIANCE 25 mg Female genital mycotic infections include the following adverse reactions: vulvovaginal mycotic infection, vaginal infection, vulvitis, vulvovaginal candidiasis, genital infection, genital candidiasis, genital infection fungal, genitourinary tract infection, vulvovaginitis, cervicitis, urogenital infection fungal, vaginitis bacterial Male genital mycotic infections include the following adverse reactions: balanoposthitis, balanitis, genital infections fungal, genitourinary tract infection, balanitis candida, scrotal abscess, penile infection

The FDA drug label does not answer the question.

From the Research

Jardiance and Candidiasis

• Jardiance, an SGLT2 inhibitor, has been associated with an increased risk of genital mycotic infections, particularly candidiasis 2, 3, 4, 5.
• The mechanism of action of SGLT2 inhibitors, which involves reducing reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria, may contribute to the increased risk of candidiasis 2, 4.
• Studies have shown that the incidence of genital mycotic infections is higher in patients taking SGLT2 inhibitors compared to those taking other diabetes medications, such as DPP4 inhibitors 4.

Why Jardiance Causes Candidiasis but Not Bacterial Infections

• The increased risk of candidiasis associated with Jardiance may be due to the fact that Candida growth and virulence are enhanced in high glucose environments 6.
• The high glucose environment created by SGLT2 inhibitors may promote the adhesion of Candida to vaginal epithelial cells, increasing the risk of infection 6.
• In contrast, bacterial infections may not be as strongly associated with Jardiance because the high glucose environment created by the medication may not have the same effect on bacterial growth and adhesion 4.

Key Findings

• SGLT2 inhibitors, including Jardiance, are associated with an increased risk of genital mycotic infections, particularly candidiasis 2, 3, 4, 5.
• The mechanism of action of SGLT2 inhibitors and the resulting high glucose environment may contribute to the increased risk of candidiasis 2, 4, 6.
• Patients taking Jardiance should be aware of the increased risk of candidiasis and take steps to prevent infection, such as practicing good personal hygiene 5.