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 that works by increasing insulin secretion and decreasing glucagon release in a glucose-dependent manner, reducing HbA1c by approximately 0.5-0.9%. 1, 2

Mechanism of Action

• Sitagliptin inhibits the DPP-4 enzyme, which normally degrades glucagon-like peptide-1 (GLP-1), thereby increasing circulating incretin levels 3, 4
• This enhancement of the incretin system stimulates insulin secretion and inhibits glucagon production in a glucose-dependent manner, meaning it only works when blood sugar is elevated 1, 4
• The glucose-dependent mechanism minimizes hypoglycemia risk when used as monotherapy 1, 5

Clinical Efficacy

• Sitagliptin reduces HbA1c by 0.5-0.9% across various patient populations 1, 2, 6
• The medication is weight-neutral, neither causing weight gain nor significant weight loss 1, 5
• It can be used as monotherapy or in combination with metformin, thiazolidinediones, sulfonylureas, or insulin 3, 2

Dosing and Administration

• Standard dose: 100 mg once daily for patients with normal renal function (eGFR ≥45 mL/min/1.73 m²) 1, 2
• Moderate renal impairment (eGFR 30-44 mL/min/1.73 m²): 50 mg once daily 1, 2
• Severe renal impairment (eGFR <30 mL/min/1.73 m²): 25 mg once daily 1, 2
• The medication requires no dose titration and can be taken with or without food 4

Safety Profile and Cardiovascular Outcomes

• The TECOS trial demonstrated cardiovascular safety with no increased risk of major adverse cardiac events or heart failure hospitalization compared to placebo 3, 1, 6
• Sitagliptin has a low risk of hypoglycemia when used alone, but increases hypoglycemia risk by approximately 50% when combined with sulfonylureas 1, 5
• Common side effects include gastrointestinal complaints (abdominal pain, nausea, diarrhea) in up to 16% of patients 2
• Unlike saxagliptin and alogliptin, sitagliptin showed neutral effects on heart failure risk 3, 1

Clinical Positioning

• Second-line therapy: Sitagliptin is recommended as second-line treatment after metformin in patients who have not achieved glycemic targets 1
• Not first-line for high-risk patients: 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 due to proven mortality and cardiovascular benefits 1
• Hospital use: Sitagliptin can be combined with basal insulin in hospitalized patients with mild-to-moderate hyperglycemia, providing similar glycemic control to basal-bolus regimens with lower hypoglycemia risk 1

Important Clinical Caveats

• Renal function monitoring: Always calculate eGFR rather than relying on serum creatinine alone, especially in elderly patients, as age-related decline in renal function may not be reflected in serum creatinine 1
• Combination with sulfonylureas: When adding sitagliptin to sulfonylurea therapy, be aware of the 50% increased hypoglycemia risk and consider reducing the sulfonylurea dose 1
• Limited cardiovascular benefit: While cardiovascular-safe, sitagliptin provides no cardiovascular benefit, unlike SGLT2 inhibitors and GLP-1 receptor agonists 3, 1
• Alternative in renal impairment: Linagliptin (another DPP-4 inhibitor) requires no dose adjustment regardless of renal function and may be simpler for patients with fluctuating kidney function 1