Do DPP4i (Dipeptidyl Peptidase-4 inhibitors) and SGLT2i (Sodium-Glucose Cotransporter 2 inhibitors) increase the risk of genitourinary infections?

DPP4i and SGLT2i Impact on Genitourinary Infections

SGLT2i increases the risk of genital mycotic infections, while DPP4i does not increase risk and may actually moderate the infection risk when used in combination with SGLT2i.

SGLT2i and Genitourinary Infection Risk

• SGLT2i therapy is associated with a significantly higher risk of genital mycotic infections (6% of patients on SGLT2i vs. 1% on placebo) 1
• Women are at substantially higher risk than men for genital infections when using SGLT2i (HR 3.64) 2
• History of prior genital infection is the strongest predictor of infection risk with SGLT2i (up to 4.38 times higher risk if infection occurred within 1 year before initiation) 2
• One-year absolute risk of genital infection with SGLT2i is highest for those with history of prior infection (females 23.7%, males 12.1%), compared to those without (females 10.8%, males 2.7%) 2

DPP4i and Genitourinary Infection Risk

• DPP4i therapy is not associated with increased risk of genitourinary infections 3
• When DPP4i and SGLT2i are used in combination, the risk of genital tract infections is approximately 50% lower compared to SGLT2i alone (risk ratio 0.51) 4
• Pharmacovigilance data shows that combination therapy with DPP4i appears to reduce the frequency of genitourinary infections associated with SGLT2i (proportional reporting ratio of 0.74) 4

Risk Factors and Management

• Key risk factors for genitourinary infections with SGLT2i include:

  • Female sex 2
  • History of prior genital infection 2
  • Unlike other diabetes medications, baseline HbA1c is not associated with infection risk for SGLT2i 2

• Management strategies for patients on SGLT2i:

  • Counsel patients on proper genital hygiene before and during therapy 5
  • Most genital mycotic infections can be treated with standard antifungal therapy without discontinuing SGLT2i 5
  • Consider temporary discontinuation of SGLT2i in severe or recurrent UTIs 5
  • Discontinue SGLT2i immediately for severe infections or Fournier's gangrene 5

Special Considerations

• Older adults (≥65 years) may not have significantly increased risk of genitourinary infections with SGLT2i compared to other antidiabetic medications like GLP1-RA 6
• SGLT2i should be used cautiously in patients with recurrent or severe urinary tract infections 1
• For patients with chronic kidney disease, SGLT2i benefits on kidney and cardiovascular outcomes generally outweigh the risk of genitourinary infections 1
• Additional research is needed to determine the role of SGLT2i in patients post-transplant, as immunosuppression may modify infection risks 1

Clinical Decision-Making Algorithm

1. Assess patient's baseline risk for genital infections:

   • Female sex (3.6× higher risk) 2
   • History of prior genital infection (up to 4.4× higher risk) 2

2. For high-risk patients (women with history of genital infections):

   • Consider combination therapy with DPP4i and SGLT2i to reduce infection risk 4
   • Provide thorough education on hygiene and early symptom recognition 5

3. For patients with recurrent genitourinary infections:

   • Consider alternative antidiabetic agents if infections become burdensome 1
   • If SGLT2i benefits outweigh risks, implement preventive strategies and close monitoring 5

4. For all patients on SGLT2i:

   • Monitor for symptoms of genitourinary infections during follow-up visits 5
   • Treat most infections with standard therapy without discontinuing SGLT2i 5
   • Discontinue SGLT2i only for severe infections or Fournier's gangrene 5

In conclusion, while SGLT2i increases risk of genital mycotic infections, combination with DPP4i appears to moderate this risk. Patient selection, education, and monitoring are key to managing this common side effect.