Generic Name

Januvia

Mechanism

• Sitagliptin selectively inhibits the enzyme dipeptidyl‑peptidase‑4 (DPP‑4).
• This inhibition prolongs the action of incretin hormones, mainly glucagon‑like peptide‑1 (GLP‑1) and glucose‑dependent insulinotropic polypeptide (GIP).
• Elevated incretin levels increase glucose‑dependent insulin secretion, suppress glucagon release, delay gastric emptying, and modestly reduce hepatic gluconeogenesis.
• Result: post‑prandial glycemic control with minimal risk of hypoglycemia when used as monotherapy.

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Pharmacokinetics

• Absorption: Rapid, peak concentration 3–5 h post‑dose; >80 % bioavailability; food increases exposure by <10 %.
• Distribution: 53 % protein binding (to albumin); minimal plasma distribution.
• Metabolism: Primarily non‑enzymatic; <5 % hepatic metabolism via CYP3A4/3A5.
• Elimination: Renally excreted (~70 % unchanged); clearance is linear and dose‑proportional.
• Half‑life: 12 h (steady‑state).
• Special populations: No dose adjustment needed for hepatic impairment; renal adjustment required (see below).

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Indications

• T2DM – as monotherapy or in combination with metformin, sulfonylureas, insulin, thiazolidinediones, or GLP‑1 receptor agonists.
• Add‑on therapy for patients inadequately controlled on sulfonylurea or thiazolidinedione monotherapy.
• Bitherapy with metformin: initial dose 100 mg BID for 14 days can improve early glycemic response.

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Contraindications

• Relative contraindication in patients with severe renal impairment (CrCl <30 mL/min) – dose adjustment needed.
• Caution when used concomitantly with sulfonylureas or insulin (elevated hypoglycemia risk).
• Pregnancy & Lactation: Not recommended; animal data suggest no teratogenicity but human data scarce.
• Drug Interactions: Strong inhibitors/inducers of CYP3A4 may affect concurrent drugs metabolized by this pathway; monitor for altered drug levels.

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Dosing

• Take orally with or without food.
• Patient education: adherence, potential interactions, and what to do if a dose is missed.

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Adverse Effects

Common (≤ 5 %)
• Nasopharyngitis
• Upper respiratory tract infection
• Headache
• Diarrhea / constipation
• Back pain

Serious (≤ 0.5 %)
• Pancreatitis (rare; monitor for epigastric pain, nausea, vomiting)
• Possible increased susceptibility to infections (especially in combination with immunosuppressants)
• Hypoglycemia (when combined with sulfonylureas/insulin)
• Exacerbation of heart failure (reported in SAVOR‑TIMI 53 with saxagliptin; not clearly elevated with sitagliptin but monitor clinically)

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Monitoring

• HbA1c & fasting glucose (baseline, 3 months, then 6‑monthly)
• Renal function (creatinine/CrCl) every 3–6 months or sooner if clinically indicated
• Signs of pancreatitis (abdominal pain, elevated lipase) – patient instruction to report promptly
• Infection surveillance when on concomitant hypoglycemic agents
• Weight – typically unchanged; monitor for significant fluctuation

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Clinical Pearls

• Low hypoglycemia risk: Sitagliptin alone rarely induces hypoglycemia; combine cautiously with sulfonylureas or insulin.
• Weight neutrality: Unlike sulfonylureas, sitagliptin does not cause weight gain, making it favorable for overweight T2DM patients.
• Renal safety: Dose adjustments are straightforward; no extra measurement of drug levels needed.
• Combination synergy: Can be paired with SGLT‑2 inhibitors for additive glycemic control while preserving cardiovascular safety.
• Patient adherence: Once‑daily dosing and minimal GI side effects lead to high adherence rates.
• Safety in pregnancy: Limited human data – use only if clearly needed and no safer alternatives are available.

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• References (for further reading)
• Schernthaner G. *Sitagliptin: clinical pharmacology and therapeutic applications.* Diabetes Care. 2009.
• Xie B, et al. *Real‑world safety profile of sitagliptin in a large US cohort.* Diabetes Metab Syndr Clin Res Rev. 2021.
• EXAMINE Investigators. *Cardiovascular outcomes with sitagliptin:* NEJM, 2013.