Generic Name

Sitagliptin

Mechanism

Sitagliptin competitively inhibits DPP‑4, an enzyme that degrades incretin hormones (GLP‑1 and GIP).
• ↑ Incretin availability → increased glucose‑dependent insulin secretion and decreased glucagon release.
• ΔHbA1c ≈ 0.9 – 1.2 % in monotherapy; additive benefit when combined with metformin or sulfonylureas.
• Effects are insulin‑stimulating only in hyperglycemic states, minimizing hypoglycemia risk.

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Pharmacokinetics

• Formulation: 100 mg tablets (100 mg oral dose).
• Absorption: ~85 % bioavailability; peak plasma concentration (~3 h).
• Distribution: 246 mL/kg; protein binding ~70 %.
• Metabolism: Minimal CYP450 involvement; mainly renal excretion.
• Half‑life: ~12 h (once‑daily dosing).
• Renal clearance: 61 % unchanged, 30 % as glucuronide metabolites.

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Indications

• Adults and adolescents ≥16 yr with T2DM uncontrolled on diet + exercise or as adjunct to other oral hypoglycemics.
• Combination therapy: with metformin, sulfonylureas, insulin, or thiazolidinediones.

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Contraindications

• Contraindicated: hypersensitivity to sitagliptin or any component.
• Renal impairment: CKD stage 4–5 (eGFR < 30 mL/min/1.73 m²) – avoid or use lowest dose per label.
• Pregnancy/Lactation: Category B – not well‑studied; use only if benefits outweigh risks.
• Concomitant use with other DPP‑4 inhibitors or gliptins—avoid overlap due to risk of hypoglycemia or pancreatitis.

Warnings
• Pancreatitis: Report any upper abdominal pain, nausea, vomiting.
• Allergic reactions: rash, angioedema, anaphylaxis.
• Infections: Upper respiratory tract infections, especially in patients on concomitant immunosuppressants.

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Dosing

• Administration: At any time of day with or without food.
• Refill: Shown under "No. of refills: 99 (???)" in many formularies.

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Adverse Effects

Common (≥ 2 %):
• Nasopharyngitis
• Headache
• Upper respiratory tract infection
• Weight Neutral (often used as a reassuring feature)

Serious (≤ 2 %):
• Acute pancreatitis (1:1,000‑3,000)
• Hypersensitivity (rash, fever, angioedema)
• Severe infections (e.g., cellulitis, candidiasis)
• Death (unlikely but reported in association with severe pancreatitis)

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Monitoring

• Baseline & Follow‑up:
• Fasting glucose & HbA1c (every 3 months)
• Serum creatinine, eGFR (trimonthly while on dialysis or CKD)
• Adverse Reaction Surveillance:
• Monitor for abdominal pain, nausea, vomiting → pancreatitis screening.
• Watch for signs of infection; consider prophylaxis in immunocompromised.

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Clinical Pearls

• Low Hypoglycemia Risk:
• Glucose‑dependent insulin release keeps hypoglycemia rare; only a concern if combined with insulin or sulfonylureas.
• Renal Dosing Simplicity:
• One‑dose adjustment (100 → 50 mg) for eGFR 30‑59 mL/min simplifies patient adherence.
• Weight Management:
• Sitagliptin is weight neutral, making it advantageous for overweight/obese T2DM patients (esp. in multimorbidity).
• Pancreatitis Signal Strength:
• Maintain a low threshold for imaging (CT/MRI) if patients report epigastric discomfort, regardless of serum amylase/lipase levels which may be normal initially.
• Drug‑Drug Interactions:
• Preserve as the majority of metabolism is via renal excretion; limited CYP inhibition.
• Avoid co‑administration with other incretin-based drugs to prevent exacerbated hypoglycemia.
• Patient Education:
• Counsel patients on recognizing signs of pancreatitis, rare anaphylaxis, and the importance of regular glucose checks, especially during illness or changes in renal function.

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• Sitagliptin remains a cornerstone oral agent in the T2DM armamentarium, combining efficacy, safety, and ease of use—critical factors in optimizing patient outcomes.