Sitagliptin Drug Class
Sitagliptin (Januvia) is a dipeptidyl peptidase-4 (DPP-4) inhibitor, an oral antihyperglycemic agent that enhances glucose-dependent insulin secretion and suppresses glucagon release by preventing the degradation of incretin hormones. 1, 2
Mechanism of Action
- DPP-4 inhibitors work by blocking the enzyme dipeptidyl peptidase-4, which normally degrades incretin hormones (GLP-1 and GIP), thereby increasing their active levels and duration of action 2, 3
- This leads to glucose-dependent insulin secretion from pancreatic beta cells and decreased glucagon secretion from alpha cells 4, 5
- The glucose-dependent mechanism means insulin release stops when glucose normalizes, minimizing hypoglycemia risk 6
Clinical Efficacy
- Sitagliptin reduces HbA1c by approximately 0.4-0.9% when used as monotherapy or in combination with other antidiabetic agents 1, 6
- The drug lowers both fasting and postprandial glucose concentrations 4, 5
- Efficacy is greatest in patients with mild-to-moderate hyperglycemia (blood glucose <180 mg/dL) 7
Safety Profile
- Sitagliptin has minimal hypoglycemia risk when used as monotherapy, though risk increases approximately 50% when combined with sulfonylureas 1, 7
- The drug is weight-neutral and generally well tolerated with adverse event rates similar to placebo 3, 8
- Cardiovascular outcomes trials (TECOS) demonstrated cardiovascular safety but no cardiovascular benefit, with neutral effects on heart failure hospitalization 9, 1
Dosing Considerations
- Standard dose is 100 mg once daily for patients with normal renal function (eGFR ≥45 mL/min/1.73 m²) 1, 2
- Dose adjustment required for renal impairment: 50 mg daily for eGFR 30-44 mL/min/1.73 m², and 25 mg daily for eGFR <30 mL/min/1.73 m² 1, 2
Clinical Positioning
- The American Diabetes Association recommends DPP-4 inhibitors as second-line therapy after metformin, or as initial combination therapy when HbA1c is ≥1.5% above target 1
- For patients with established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease with albuminuria, SGLT2 inhibitors or GLP-1 receptor agonists are strongly preferred over DPP-4 inhibitors due to proven cardiovascular and renal benefits 9, 1
- DPP-4 inhibitors remain reasonable options for patients without cardiovascular or renal comorbidities when metformin alone is insufficient 7
Important Caveats
- Unlike saxagliptin and alogliptin, sitagliptin has not been associated with increased heart failure hospitalization risk 9, 1
- Regular monitoring of renal function is needed to adjust dosing appropriately 1
- The drug can be used in combination with metformin, thiazolidinediones, sulfonylureas, or insulin 1, 8