DPP-4 Inhibitor Examples for Type 2 Diabetes
The available DPP-4 inhibitors (gliptins) for type 2 diabetes include sitagliptin (Januvia), linagliptin (Tradjenta), saxagliptin (Onglyza), alogliptin (Nesina), and vildagliptin (Galvus - not available in the US). 1, 2
Available DPP-4 Inhibitors
First-Line DPP-4 Inhibitor Options
Sitagliptin (Januvia)
- Standard dose: 100 mg once daily 1
- Requires dose adjustment in renal impairment: 50 mg daily if eGFR 30-44 mL/min/1.73 m²; 25 mg daily if eGFR <30 mL/min/1.73 m² 1
- Demonstrated cardiovascular safety in TECOS trial with neutral heart failure risk 1
- Most extensively studied DPP-4 inhibitor with established safety profile 3
Linagliptin (Tradjenta)
- Standard dose: 5 mg once daily for all patients 1
- Major advantage: No dose adjustment required regardless of renal or hepatic function 1, 4
- Minimal renal excretion makes it ideal for patients with chronic kidney disease 1
- Neutral cardiovascular safety profile in CARMELINA trial 1
Saxagliptin (Onglyza)
- Standard dose: 5 mg once daily 5
- Requires dose reduction to 2.5 mg daily if eGFR ≤45 mL/min/1.73 m² 1
- Critical warning: Associated with 27% increased risk of heart failure hospitalization in SAVOR TIMI-53 trial 1, 6
- Should be avoided in patients with heart failure risk or established heart failure 1, 6
- Metabolized by CYP3A4/5, requiring dose adjustment with strong CYP3A4/5 inhibitors 5, 7
Alogliptin (Nesina)
- Requires dose adjustment based on renal function 1
- Also associated with increased heart failure hospitalization risk 1
- Should be avoided in patients with cardiac disease 1
Vildagliptin (Galvus)
- Standard dose: 50 mg twice daily 2, 8
- Not available in the United States 1
- Available in other countries with similar efficacy to other DPP-4 inhibitors 3, 8
Clinical Characteristics of DPP-4 Inhibitors as a Class
Efficacy Profile
- Reduce HbA1c by approximately 0.4-0.9% 1, 3
- Less potent than GLP-1 receptor agonists or SGLT2 inhibitors 1
- Work through glucose-dependent mechanism, enhancing insulin secretion and suppressing glucagon 5
Safety Profile
- Minimal hypoglycemia risk when used as monotherapy 1, 3
- Hypoglycemia risk increases approximately 50% when combined with sulfonylureas 1
- Weight-neutral (no weight gain or loss) 9, 2
- Generally well-tolerated with rare side effects 9
Clinical Positioning
- Recommended as second-line therapy after metformin 9
- Can be used in dual or triple combination therapy 9, 2
- Not first-line for patients with established cardiovascular disease, heart failure, or chronic kidney disease—GLP-1 receptor agonists or SGLT2 inhibitors preferred in these populations 1, 6
Clinical Decision Algorithm for Selecting Among DPP-4 Inhibitors
Step 1: Assess Renal Function
- eGFR ≥45 mL/min/1.73 m²: Any DPP-4 inhibitor acceptable, but linagliptin preferred for simplicity 1
- eGFR 30-44 mL/min/1.73 m²: Linagliptin 5 mg daily (no adjustment) or sitagliptin 50 mg daily 1
- eGFR <30 mL/min/1.73 m²: Linagliptin 5 mg daily (preferred) or sitagliptin 25 mg daily 1
Step 2: Assess Cardiovascular Risk
- Heart failure risk or established heart failure: Avoid saxagliptin and alogliptin; use sitagliptin or linagliptin 1, 6
- Established atherosclerotic cardiovascular disease: Consider GLP-1 receptor agonist or SGLT2 inhibitor instead of DPP-4 inhibitor 1, 6
Step 3: Consider Drug Interactions
- Patients on strong CYP3A4/5 inhibitors (ketoconazole, diltiazem): Avoid saxagliptin or reduce dose; prefer linagliptin or sitagliptin 5, 7
- Polypharmacy concerns: Linagliptin has minimal drug-drug interactions 1, 7
Important Clinical Caveats
- All DPP-4 inhibitors have demonstrated cardiovascular safety but no cardiovascular benefit 1
- When adding DPP-4 inhibitor to sulfonylurea therapy, consider reducing sulfonylurea dose to minimize hypoglycemia risk 1, 7
- DPP-4 inhibitors can be combined safely with metformin, thiazolidinediones, or insulin 9, 2
- Rare but reported adverse effects include pancreatitis and musculoskeletal side effects 1
- For patients requiring weight loss (BMI ≥30 kg/m²), GLP-1 receptor agonists are superior to DPP-4 inhibitors 6, 4