Antidiabetic medications and risk of fungal infections
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Diabetes, Antidiabetic Medications, and Fungal Infection Risk
People with diabetes are at a higher risk of developing fungal infections compared to those without diabetes. This increased risk is mainly due to weakened immune function and metabolic changes associated with diabetes, which make it easier for fungi like Candida and Aspergillus to cause infections. Studies show that diabetic individuals have a much higher prevalence of fungal infections, especially in the mouth, toes, urine, and other body sites, with Candida species being the most common culprit. These infections are also more likely to be resistant to common antifungal drugs such as fluconazole and ketoconazole, making treatment more challenging for diabetic patients 758.
SGLT2 Inhibitors and Genital Fungal Infections
Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a class of antidiabetic medications, are linked to an increased risk of genital fungal infections. Research shows that women and individuals with a prior history of genital fungal infections are especially at risk when treated with SGLT2 inhibitors like dapagliflozin. The risk is not significantly affected by age, diabetes duration, body mass index, or other factors, but is clearly higher in women and those with previous infections 38. This association is important for clinicians to consider when prescribing SGLT2 inhibitors to diabetic patients.
Sulfonylureas and Anti-Inflammatory Effects
Some second-generation sulfonylurea antidiabetic drugs, such as glyburide, glisoxepide, gliquidone, and glimepiride, have shown anti-inflammatory effects that may help reduce immune system overreactions during fungal infections like vaginal candidiasis. These drugs can inhibit the release of inflammatory molecules (like IL-1β) during Candida albicans infection, but they do not directly affect fungal growth or survival. This suggests that sulfonylureas might help manage the immune response in fungal infections, though they do not prevent the infection itself .
Diabetes as a Risk Factor for Invasive Fungal Infections
Diabetes itself is a significant risk factor for invasive fungal infections, especially in people with other health conditions such as connective tissue diseases. The risk is even higher when combined with other factors like lung or kidney disease, use of immunosuppressive drugs, or high-dose glucocorticoids. These findings highlight the need for careful monitoring and preventive strategies in diabetic patients, particularly those with additional risk factors .
Challenges in Treating Fungal Infections in Diabetic Patients
Treating fungal infections in diabetic patients is complicated by changes in how the body processes medications. Diabetes can alter the pharmacokinetics and pharmacodynamics of antifungal drugs, making it harder to achieve effective treatment. There is also a higher rate of antifungal resistance among fungal isolates from diabetic patients, which further complicates therapy. More research is needed to optimize antifungal dosing and treatment strategies for this population 57.
Fungal Metabolites as Potential Antidiabetic Agents
Interestingly, some research is exploring the use of fungal metabolites as potential antidiabetic agents. These natural compounds, derived from various fungi, have shown the ability to inhibit enzymes involved in diabetes, such as protein tyrosine phosphatase 1B (PTP1B). While this is a promising area for drug development, it is not directly related to the risk of fungal infections from current antidiabetic medications, but rather highlights the complex relationship between fungi and diabetes management 46.
Conclusion
Diabetic patients are more susceptible to fungal infections, and certain antidiabetic medications, especially SGLT2 inhibitors, further increase this risk, particularly for genital fungal infections. Second-generation sulfonylureas may help control inflammation during fungal infections but do not prevent them. Treating fungal infections in diabetic patients is challenging due to altered drug handling and increased resistance. Clinicians should be aware of these risks and tailor diabetes and infection management accordingly.
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