In a male patient taking a sodium‑glucose cotransporter‑2 (SGLT2) inhibitor, are balanoposthitis and upper respiratory symptoms common adverse effects?

SGLT2 Inhibitors and Balanoposthitis/Upper Respiratory Symptoms

Yes, SGLT2 inhibitors significantly increase the risk of balanoposthitis in male patients (approximately 3-fold increase), but they do NOT increase the risk of upper respiratory tract infections. 1

Balanoposthitis Risk Profile

Male patients taking SGLT2 inhibitors face an approximately 2.7-fold increased risk of genital infections including balanitis and balanoposthitis compared to other diabetes medications. 2 The absolute excess risk is 11.9 additional cases per 1,000 person-years in men. 2

Key Risk Factors for Genital Infections in Males:

• Prior history of genital infection is the strongest predictor: men with infection history <1 year ago have a 12.1% one-year absolute risk versus 2.7% in those without prior history 3
• Uncircumcised males are at higher risk than circumcised males 4
• Age ≥60 years increases risk 3.3-fold compared to younger patients 2
• Importantly, baseline HbA1c level does NOT predict infection risk with SGLT2 inhibitors (unlike other diabetes medications) 3

Clinical Characteristics of Genital Infections:

The genital infections associated with SGLT2 inhibitors are typically mild candidal infections (balanitis/balanoposthitis) that respond to brief courses of topical or oral antifungal therapy and rarely recur. 1 Most infections do not require discontinuation of the SGLT2 inhibitor. 5, 6

The increased risk appears within the first month of treatment and remains elevated throughout therapy. 2 There are no meaningful differences in genital infection rates between individual SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin). 2

Upper Respiratory Tract Infections

SGLT2 inhibitors do NOT increase the risk of upper respiratory tract infections or other respiratory infections. 7 Large randomized controlled trials including EMPA-REG OUTCOME and CANVAS showed no difference in respiratory infection rates between SGLT2 inhibitors and placebo. 1

Management Algorithm for Balanoposthitis

Prevention:

• Counsel all male patients on proper genital hygiene before initiating SGLT2 inhibitor therapy 5, 6
• Educate patients about early symptoms (redness, itching, discharge) to facilitate prompt treatment 5

Treatment of Active Infection:

• Treat with standard topical antifungal creams (clotrimazole, miconazole) or oral fluconazole 150 mg single dose 5
• Continue SGLT2 inhibitor during treatment of mild to moderate infections 5, 6
• Resume SGLT2 inhibitor after complete resolution if temporarily held 5

Recurrent Infections (≥4 episodes/year):

• Consider temporary discontinuation if infections markedly impair quality of life 5
• Implement maintenance antifungal therapy (weekly fluconazole 150 mg for 6 months after induction) 5
• Reassess risk-benefit ratio of continuing SGLT2 inhibitor therapy 5, 6

Severe Infections:

• Immediately discontinue SGLT2 inhibitor for Fournier's gangrene (necrotizing fasciitis of the perineum), which requires urgent surgical debridement and broad-spectrum antibiotics 5, 8
• While extremely rare (12 cases over 5 years among 1.7 million patients), Fournier's gangrene is a medical emergency 1

Critical Clinical Decision Points

The cardiovascular and renal benefits of SGLT2 inhibitors generally outweigh the risk of genital infections in most patients. 5, 6, 9 SGLT2 inhibitors reduce all-cause mortality by 49% and heart failure hospitalization by 36-39%. 1

When to Avoid SGLT2 Inhibitors:

• Strong consideration should be given to avoid SGLT2 inhibitors in male patients with a history of severe, recurrent genital infections 4
• Immunocompromised patients may require more careful monitoring 1, 5

When to Continue Despite Infection Risk:

• For patients with chronic kidney disease (eGFR ≥20 mL/min/1.73 m² with albuminuria ≥200 mg/g) or heart failure, Class 1A recommendation supports continued SGLT2 inhibitor therapy 5
• Infection risk alone rarely justifies permanent discontinuation given the substantial mortality benefit 5

Common Pitfalls

• Do not confuse symptoms of euglycemic ketoacidosis (dyspnea, nausea, vomiting, abdominal pain) with genitourinary infection symptoms 1, 5
• Do not assume high HbA1c increases genital infection risk with SGLT2 inhibitors—this relationship does not exist for this drug class 3
• Do not routinely discontinue SGLT2 inhibitors for mild genital infections—most resolve with standard antifungal therapy while continuing the medication 5, 6
• Withhold SGLT2 inhibitors during acute illness, prolonged fasting, or surgery to reduce ketoacidosis risk, not infection risk 5