Why Sitagliptin Does NOT Need to Be Held During Infections
Sitagliptin (a DPP-4 inhibitor) is generally well tolerated and can be continued during acute infections, unlike metformin and SGLT2 inhibitors which must be stopped. 1
Key Distinction: DPP-4 Inhibitors vs. Other Diabetes Medications
The confusion likely stems from "sick day rules" that apply to other diabetes medications, not DPP-4 inhibitors:
Medications That MUST Be Held During Acute Illness 1
- SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) – risk of dehydration and diabetic ketoacidosis 1
- Metformin – risk of lactic acidosis if dehydration or acute kidney injury develops 1
- ACE inhibitors/ARBs – risk of acute kidney injury with volume depletion 1
- Diuretics (loop, thiazide, potassium-sparing) – worsen dehydration 1
- NSAIDs – increase acute kidney injury risk 1
Medications That Can Be Continued 1
- DPP-4 inhibitors (sitagliptin, linagliptin, saxagliptin, alogliptin) – "generally well tolerated and can be continued" 1
- Insulin – should not be stopped, though doses may need adjustment 1
Why Sitagliptin Is Safe During Infections
DPP-4 inhibitors work in a glucose-dependent manner, meaning they only stimulate insulin secretion when blood glucose is elevated, which minimizes hypoglycemia risk even during reduced oral intake. 1, 2
Key safety features:
- No dehydration risk – unlike SGLT2 inhibitors which cause osmotic diuresis 1
- No lactic acidosis risk – unlike metformin 1
- Minimal hypoglycemia risk when used alone 1, 2
- Weight neutral – no fluid retention concerns 1, 2
The One Caveat: Renal Function Monitoring
While sitagliptin can be continued during infection, you must monitor renal function because acute kidney injury may require dose adjustment. 1, 3, 4
Dose Adjustment Algorithm Based on eGFR 3, 4
- eGFR ≥50 mL/min/1.73 m² → 100 mg daily (no change)
- eGFR 30-50 mL/min/1.73 m² → reduce to 50 mg daily
- eGFR <30 mL/min/1.73 m² → reduce to 25 mg daily
If acute kidney injury develops during infection (common with dehydration), reassess renal function and adjust the sitagliptin dose accordingly—but do not automatically discontinue it. 1, 3, 4
Practical Clinical Approach During Acute Infection
Continue Sitagliptin If: 1
- Patient can maintain oral fluid intake
- No severe symptoms (reduced consciousness, severe vomiting, hypotension)
- Renal function stable or only mildly decreased
Monitor Closely: 1
- Blood glucose every 4-6 hours (if on insulin or sulfonylurea)
- Signs of dehydration (lightheadedness, orthostasis, decreased urine output)
- Renal function if illness persists >24-48 hours
Adjust Other Medications: 1
- Stop SGLT2 inhibitors and metformin immediately
- Hold sulfonylureas if blood glucose is low or patient not eating
- Increase insulin by 10-20% if blood glucose elevated
Common Pitfall to Avoid
The most common error is applying "sick day rules" meant for SGLT2 inhibitors and metformin to all diabetes medications. 1 The 2020 Lancet COVID-19 guidance explicitly states DPP-4 inhibitors "are generally well tolerated and can be continued" during acute illness, in direct contrast to SGLT2 inhibitors and metformin which should be stopped. 1
The 2023 international Delphi consensus on sick day medication guidance reached agreement on withholding SGLT2 inhibitors, metformin, ACE inhibitors/ARBs, and diuretics—but did NOT reach consensus to include DPP-4 inhibitors in medications to withhold. 1
Alternative: Linagliptin for Simplicity
If managing dose adjustments during acute illness seems complex, consider switching to linagliptin (another DPP-4 inhibitor) which requires no dose adjustment regardless of renal function, even in dialysis. 3, 2 This eliminates the need to recalculate doses if kidney function fluctuates during infection.