From the Guidelines
SGLT2 inhibitors can affect the skin, increasing the risk of genital mycotic infections, such as vulvovaginal candidiasis in women and balanitis in men, as well as other skin-related adverse effects like cutaneous candidiasis, necrotizing fasciitis, and Fournier's gangrene. The mechanism of action of SGLT2 inhibitors, which involves increasing glucose excretion in the urine, creates a favorable environment for fungal growth, leading to these skin-related adverse effects 1.
- Genital mycotic infections are a common adverse effect of SGLT2 inhibitors, with a significant increase in risk compared to placebo, as seen in the EMPA-REG OUTCOME trial 1 and other studies 1.
- Cutaneous candidiasis and other fungal infections can also occur, although the risk is lower compared to genital mycotic infections 1.
- Necrotizing fasciitis and Fournier's gangrene are rare but serious skin-related adverse effects associated with SGLT2 inhibitors, with a few reported cases in the literature 1.
- Dose and renal function are important considerations when using SGLT2 inhibitors, as the dose should be reduced in patients with moderate renal impairment and discontinued in severe renal impairment to minimize the risk of adverse effects 1.
- Sex-related differences in the risk of skin-related adverse effects have been observed, with women experiencing a higher incidence of genital mycotic infections and urosepsis compared to men 1.
From the Research
SGLT2 Inhibitors and Skin Effects
- SGLT2 inhibitors have been associated with skin disorders, including rash, photosensitivity, and urticaria 2
- A study using ipragliflozin found that it reduces the expression of genes involved in skin barrier and moisturizing functions, which may contribute to skin disorders 3
- Another study suggested that ipragliflozin-specific serious skin disorders may be related to its interaction with melanin and its retention in skin tissue 4
- However, a pooled post hoc analysis of the CANVAS Program and CREDENCE trials found that canagliflozin, an SGLT2 inhibitor, does not increase the risk of non-genital skin and soft tissue infections in people with type 2 diabetes mellitus 5
Skin-Related Adverse Events
- Skin and subcutaneous tissue disorders have been reported as adverse events with SGLT2 inhibitors, with a higher reporting odds ratio for ipragliflozin compared to other SGLT2 inhibitors 2, 4
- Severe adverse skin events have been reported, mainly in females aged 18-65 using SGLT2 inhibitors as a single antidiabetic regimen 2
- However, not all SGLT2 inhibitors have been associated with an increased risk of skin-related adverse events, with canagliflozin showing no significant difference in non-genital SSTI rates compared to placebo 5
Mechanisms and Risk Factors
- The mechanisms underlying the association between SGLT2 inhibitors and skin disorders are not fully understood, but may involve changes in skin microenvironment and interaction with melanin 3, 4
- Risk factors for non-genital SSTIs, including younger age, male sex, higher body mass index, and lower estimated glomerular filtration rate, have been identified 5