What is Januvia (sitagliptin)?

What is Januvia (Sitagliptin)?

Januvia (sitagliptin) is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor approved by the FDA for treating type 2 diabetes mellitus that works by increasing incretin hormone levels to enhance glucose-dependent insulin secretion and suppress glucagon release. 1, 2

Mechanism of Action

• Sitagliptin selectively inhibits the DPP-4 enzyme, which normally degrades incretin hormones like glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). 3, 4
• By preventing incretin degradation, sitagliptin increases insulin secretion and decreases glucagon secretion in a glucose-dependent manner, meaning it only works when blood glucose is elevated. 5, 6
• This glucose-dependent mechanism results in minimal hypoglycemia risk when used as monotherapy. 2, 7

Clinical Efficacy

• Sitagliptin reduces HbA1c by approximately 0.4% to 0.9% across clinical trials. 2
• It effectively lowers both fasting plasma glucose and postprandial glucose excursions. 6, 4
• The medication is weight-neutral, neither causing weight gain nor weight loss. 2, 7

Dosing and Administration

• Standard dose: 100 mg once daily, taken orally without regard to meals. 3, 5
• Renal impairment dosing: 2, 3
  • eGFR ≥45 mL/min/1.73 m²: 100 mg daily (no adjustment needed)
  • eGFR 30-44 mL/min/1.73 m²: 50 mg daily
  • eGFR <30 mL/min/1.73 m²: 25 mg daily
• No dose titration or home blood glucose monitoring is required for initiation. 5

Clinical Use and Positioning

• Sitagliptin is FDA-approved as monotherapy or in combination with metformin, thiazolidinediones, sulfonylureas, or insulin. 3, 7
• Guidelines recommend it as second-line therapy after metformin in patients with type 2 diabetes who have not achieved glycemic targets. 2
• In hospitalized patients with mild-to-moderate hyperglycemia (blood glucose <11.1 mmol/L or <200 mg/dL), sitagliptin plus basal insulin achieves similar glycemic control to basal-bolus insulin regimens with significantly lower hypoglycemia risk. 1, 2

Safety Profile and Contraindications

• Common side effects: Gastrointestinal complaints (abdominal pain, nausea, diarrhea) occur in up to 16% of patients, upper respiratory infections, headache. 3, 6
• Hypoglycemia risk: Minimal when used alone, but increases approximately 50% when combined with sulfonylureas. 2
• Absolute contraindication: History of serious hypersensitivity reaction to sitagliptin, including anaphylaxis or angioedema. 8

Cardiovascular Safety

• The TECOS trial demonstrated that sitagliptin has a neutral effect on cardiovascular events and heart failure hospitalization, making it safe but not beneficial for cardiovascular outcomes. 1, 2
• Unlike saxagliptin and alogliptin (other DPP-4 inhibitors), sitagliptin did not increase heart failure hospitalization risk. 1, 2
• However, sitagliptin provides no cardiovascular benefit, unlike SGLT-2 inhibitors or GLP-1 receptor agonists. 2

Important Clinical Caveats

• For patients with established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease with albuminuria, SGLT-2 inhibitors or GLP-1 receptor agonists are strongly preferred over sitagliptin due to proven cardiovascular and renal benefits. 2
• Sitagliptin is less effective in patients with higher baseline HbA1c values, with treatment failure independently associated with higher HbA1c (odds ratio 1.3 per 1% increase). 1, 2
• When combined with sulfonylureas or insulin, monitor closely for hypoglycemia as risk increases substantially. 2
• Regular monitoring of renal function is needed to adjust dosing appropriately. 2