Can Vildagliptin (Dipeptidyl peptidase-4 inhibitor) cause Urinary Tract Infections (UTIs)?

Vildagliptin and Urinary Tract Infections

Based on current evidence, vildagliptin (a DPP-4 inhibitor) is not associated with an increased risk of urinary tract infections (UTIs), unlike SGLT2 inhibitors which are known to cause genitourinary infections. 1

DPP-4 Inhibitors and UTI Risk

• DPP-4 inhibitors, including vildagliptin, work by increasing endogenous GLP-1 levels through inhibition of the DPP-4 enzyme, enhancing insulin secretion and inhibiting glucagon secretion in a glucose-dependent manner 1
• The common adverse effects of DPP-4 inhibitors do not include UTIs in the major guidelines and clinical studies 1
• The primary side effects of vildagliptin reported in clinical trials include headache, nasopharyngitis, cough, constipation, dizziness, and increased sweating - not UTIs 2

Comparison with SGLT2 Inhibitors

• Unlike DPP-4 inhibitors, SGLT2 inhibitors (such as dapagliflozin, empagliflozin, and canagliflozin) are well-documented to cause genitourinary tract infections 1
• SGLT2 inhibitors reduce glucose levels by inhibiting renal tubular SGLT2, promoting urinary glucose excretion, which creates an environment favorable for bacterial growth 1
• Studies show that patients treated with SGLT2 inhibitors have a 3.70 higher risk of UTI compared to those treated with non-SGLT2 inhibitors (95% CI 2.60-5.29) 3
• The incidence rate of UTI with SGLT2 inhibitors has been reported as high as 33.49% compared to 11.72% in non-SGLT2 inhibitor groups 3

Clinical Considerations for DPP-4 Inhibitors

• Vildagliptin and other DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin) reduce HbA1c levels by 0.4% to 0.9% 1
• DPP-4 inhibitors alone do not increase the risk of hypoglycemia and have a neutral or mild effect on weight gain 1
• When prescribing vildagliptin for patients with renal dysfunction, dosage must be reduced according to medication instructions 1
• The VERIFY trial demonstrated that initial combination therapy of metformin and vildagliptin is superior to sequential addition of medications for extending primary and secondary failure 1

Monitoring and Management

• When choosing antidiabetic medications for patients with a history of recurrent UTIs, SGLT2 inhibitors should be used with caution, while DPP-4 inhibitors like vildagliptin represent a safer alternative 1
• For patients at high risk of UTIs (female gender, older age), DPP-4 inhibitors may be preferred over SGLT2 inhibitors 3
• Regular monitoring for signs and symptoms of UTIs is recommended for all diabetic patients, regardless of medication choice, as diabetes itself is a risk factor for UTIs 4

Special Populations

• In older adults with diabetes, medication choice should consider the risk of adverse effects including UTIs 1
• For patients with renal dysfunction, vildagliptin dosage must be adjusted, but it does not increase UTI risk 1
• The dipeptidyl peptidase-4 inhibitor linagliptin requires no dosage adjustments in patients with liver or renal insufficiency 1

In conclusion, while SGLT2 inhibitors are clearly associated with an increased risk of genitourinary infections, the available evidence does not indicate that vildagliptin or other DPP-4 inhibitors increase the risk of UTIs in patients with type 2 diabetes mellitus.