Is it advisable to switch a patient with type 2 diabetes (T2D) and frequent urinary tract infections (UTIs) from a Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor to a Dipeptidyl Peptidase-4 (DPP4) inhibitor, such as sitagliptin or saxagliptin?

Switching from SGLT2 Inhibitor to DPP-4 Inhibitor in Patients with Recurrent UTIs

Yes, switching from an SGLT2 inhibitor to a DPP-4 inhibitor is advisable for patients with type 2 diabetes experiencing frequent urinary tract infections, as recurrent genital or urinary infections are a recognized indication to discontinue SGLT2 inhibitors and consider alternative glucose-lowering agents. 1

When to Switch: Clinical Decision Algorithm

SGLT2 Inhibitors Should Be Discontinued If:

• History of recurrent genital candidiasis 1
• Recurrent urinary tract infections (the clinical scenario in question) 1
• History of diabetic ketoacidosis 1
• Active diabetic foot ulcers or severe peripheral arterial disease (particularly with canagliflozin) 1
• eGFR consistently <30 mL/min/1.73 m² (though this threshold is evolving) 1

Evidence on UTI Risk with SGLT2 Inhibitors:

The mechanism of SGLT2 inhibitors creates glucosuria, which theoretically increases infection risk. However, the evidence is mixed:

• Real-world data shows increased UTI incidence: One Thai observational study found UTI incidence of 33.49% in SGLT2 inhibitor users versus 11.72% in non-users, with a 3.70-fold higher risk (95% CI 2.60-5.29) 2
• Clinical trial data is more reassuring: Pooled safety data from 12 dapagliflozin trials showed only modest increases in diagnosed UTIs (4.3-5.7% vs 3.7% placebo), with most infections being mild-to-moderate and responding to standard treatment 3
• Recent cross-sectional data: A 2024 study of 328 patients found no statistical difference in UTI rates between SGLT2 inhibitor users and non-users 4

Clinical interpretation: While controlled trials show minimal risk, real-world practice reveals that some patients do experience problematic recurrent UTIs. Guidelines appropriately recognize this as a reason to switch therapy 1.

DPP-4 Inhibitor Selection

First Choice: Linagliptin or Sitagliptin

Linagliptin is preferred if:

• eGFR <45 mL/min/1.73 m² - requires no dose adjustment at any level of renal function 1, 5
• Simplicity of dosing is prioritized (5 mg once daily regardless of kidney function) 5

Sitagliptin is appropriate if:

• eGFR ≥45 mL/min/1.73 m² - standard 100 mg once daily 5
• eGFR 30-44 mL/min/1.73 m² - reduce to 50 mg once daily 5
• eGFR <30 mL/min/1.73 m² - reduce to 25 mg once daily 5

Avoid Saxagliptin in This Context:

• Saxagliptin increases heart failure hospitalization risk by 27% (HR 1.27,95% CI 1.07-1.51) 1, 5, 6
• Not recommended in patients with type 2 diabetes and high risk of heart failure 1, 5

Important Caveats When Making This Switch

1. Cardiovascular and Renal Protection is Lost

This is the most critical consideration:

• SGLT2 inhibitors reduce cardiovascular death, heart failure hospitalization, and slow CKD progression 1
• DPP-4 inhibitors are cardiovascular-neutral - they show safety but no benefit for major adverse cardiovascular events or mortality 1, 5
• If the patient has established ASCVD, heart failure, or CKD with albuminuria, strongly consider GLP-1 receptor agonists instead of DPP-4 inhibitors, as they provide cardiovascular and renal benefits without the UTI risk 1

2. Reduced Glucose-Lowering Efficacy

• SGLT2 inhibitors reduce HbA1c by approximately 0.5-1.0% 1
• DPP-4 inhibitors reduce HbA1c by approximately 0.4-0.9% 5, 7
• The glucose-lowering effect is comparable but slightly less potent with DPP-4 inhibitors 5

3. Weight Effects Differ

• SGLT2 inhibitors promote weight loss (2-3 kg on average) 1
• DPP-4 inhibitors are weight-neutral 5, 7

4. Discontinue Any Existing DPP-4 Inhibitor Before Starting GLP-1 RA

If you later decide to add a GLP-1 receptor agonist for cardiovascular protection, you must discontinue the DPP-4 inhibitor first, as they should never be used together 1

Practical Implementation Steps

At the Time of Switch:

1. Stop the SGLT2 inhibitor immediately 1
2. Start DPP-4 inhibitor (linagliptin 5 mg daily or sitagliptin 100 mg daily if eGFR ≥45) 5
3. If on sulfonylurea or insulin: Consider reducing sulfonylurea dose by 50% or basal insulin by 20% to minimize hypoglycemia risk, though DPP-4 inhibitors have minimal hypoglycemia risk as monotherapy 1, 5
4. Continue metformin if already prescribed and eGFR ≥30 mL/min/1.73 m² 1

Monitoring After Switch:

• Recheck HbA1c in 3 months to assess glycemic control 5
• Monitor for UTI resolution - if UTIs persist, investigate other causes (poor glycemic control, anatomical abnormalities, incomplete bladder emptying) 4
• Monitor renal function at least every 3-6 months if eGFR <60 mL/min/1.73 m² 1
• Reassess cardiovascular risk factors - if ASCVD, heart failure, or progressive CKD develops, strongly reconsider adding GLP-1 RA 1

Alternative Strategy: Consider GLP-1 Receptor Agonist Instead

For patients with:

• Established ASCVD 1
• Heart failure 1, 6
• CKD with albuminuria 1
• Need for substantial weight loss 1

GLP-1 receptor agonists (liraglutide, semaglutide, dulaglutide) are superior to DPP-4 inhibitors because they:

• Reduce major adverse cardiovascular events and cardiovascular death 1
• Do not increase UTI risk 1
• Provide greater HbA1c reduction (1.0-1.5%) 1
• Promote significant weight loss (3-5 kg) 1

The main barriers are cost, need for injection (though oral semaglutide is available), and gastrointestinal side effects (nausea) 1.