Bittersweet: infective complications of drug-induced glycosuria in patients with diabetes mellitus on SGLT2-inhibitors: two case reports

Abstract

Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). We present two cases with underlying abnormalities of the urogenital tract in which the GMI were complicated and necessitated cessation of the SGLT2 inhibitor. Case presentations Both cases are patients with T2DM on empagliflozin, an SGLT2 inhibitor. The first case is a 64 year old man with Candida albicans balanitis and candidemia who was found to have an obstructing renal calculus and prostatic abscess requiring operative management. The second case describes a 72 year old man with Candida glabrata candidemia who was found to have prostatomegaly, balanitis xerotica obliterans with significant urethral stricture and bladder diverticulae. His treatment was more complex due to fluconazole resistance and concerns about urinary tract penetration of other antifungals. Both patients recovered following prolonged courses of antifungal therapy and in both cases the SGLT2 inhibitor was ceased. Conclusions Despite their cardiovascular benefits, SGLT2 inhibitors can be associated with complicated fungal infections including candidemia and patients with anatomical abnormalities of the urogenital tract may be more susceptible to these infections as demonstrated in these cases. Clinicians should be aware of their mechanism of action and associated risk of infection and prior to prescription, assessment of urogenital anatomical abnormalities should be performed to identify patients who may be at risk of complicated infection.

The rationale for the need to study sodium-glucose co-transport 2 inhibitor usage in peritoneal dialysis patients

“…47 Another adverse effect that has consistently been reported involves genital mycotic infections related to glycosuria. 48 SGLT2 inhibitors have also been associated with rare but life-threatening Fournier’s gangrene of the perineum. 49 However, since the glycosuric effect of this drug dissipates beyond stage 3 CKD, the risk of euglycaemic DKA, genitourinary infections and even hypoglycaemia should not be of concern in the PD population.…”

Growing importance of urogenital candidiasis in individuals with diabetes: A narrative review

“…Even novel hypoglycemic agents that can induce glycosuria, most notably already mentioned SGLT2 inhibitors, can also increase the risk of genital candidiasis in males (Figure 2 ). For example, a recent report by Bartolo et al [ 73 ] showed the development of balanitis due to C. albicans and subsequent candidemia but also the potential role of other species such as C. glabrata . A severe form of balanoposthitis caused by C. albicans after treatment with SGLT2 was also described in a 57-year-old with type 2 diabetes coupled with oral candidiasis[ 74 ].…”

Sodium-glucose Co-transporter-2 Inhibitors Causing Candida tropicalis Fungemia and Renal Abscess

“…Despite the broad benefits of SGLT2i, several adverse events have been reported, including euglycemic diabetic ketoacidosis, urinary tract infections (UTIs), genital mycotic infections with all the agents, and a risk of lower limb amputation with canagliflozin specifically [ 5 ]. A handful of case reports have described the occurrence of severe invasive fungal infections due to Candida in patients on SGLT2i [ 6‐9 ]. We describe a case of invasive Candida infection in a patient on empagliflozin following a prostate biopsy.…”