Za Pharmacy
Drugs, Supplies and Delivery
Sitagliptin and Sitagliptin/Metformin
Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and its fixed-dose combination with metformin (Sitagliptin/Metformin) are oral antidiabetic agents designed to manage type 2 diabetes mellitus (T2DM). These medications synergistically address hyperglycemia through complementary mechanisms, enhancing insulin secretion and improving insulin sensitivity. This article integrates evidence from the British National Formulary (BNF), Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology to detail their mechanisms, clinical uses, dosing, side effects, precautions, drug interactions, and pharmaceutical nomenclature.
- Sitagliptin (DPP-4 Inhibitor):
- Inhibits the enzyme DPP-4, which degrades incretin hormones (GLP-1 and GIP). By prolonging incretin activity, it:
- Enhances Glucose-Dependent Insulin Secretion: Stimulates pancreatic β-cells to release insulin in response to elevated blood glucose.
- Suppresses Hepatic Glucose Production: Reduces glucagon secretion from α-cells (Lippincott).
- Unlike sulfonylureas, it carries a low risk of hypoglycemia when used alone (Lange).
- Inhibits the enzyme DPP-4, which degrades incretin hormones (GLP-1 and GIP). By prolonging incretin activity, it:
- Metformin (Biguanide):
- Reduces Hepatic Gluconeogenesis: Activates AMP-activated protein kinase (AMPK), decreasing glucose production.
- Improves Insulin Sensitivity: Enhances glucose uptake in peripheral tissues (BNF).
Synergy: The combination targets both insulin deficiency (via Sitagliptin) and insulin resistance (via Metformin), offering comprehensive glycemic control.
- BNF-Approved Indications:
- Sitagliptin Monotherapy: For T2DM when metformin is contraindicated or poorly tolerated.
- Sitagliptin/Metformin Combination:
- First-line therapy for patients requiring dual-pathway intervention.
- Adjunct to diet/exercise or other agents (e.g., insulin, sulfonylureas) (BNF).
- Contraindications:
- Sitagliptin: Hypersensitivity to DPP-4 inhibitors.
- Metformin: Severe renal impairment (eGFR <30 mL/min/1.73m²), acidosis, hepatic failure (BNF).
- Sitagliptin Monotherapy:
- Adults: 100 mg once daily, with or without food.
- Renal Adjustment:
- eGFR 30–50 mL/min: 50 mg daily.
- eGFR <30 mL/min: 25 mg daily (BNF).
- Sitagliptin/Metformin Combination:
- Available Strengths: 50/500 mg, 50/850 mg, 50/1000 mg.
- Dosing:
- Initial: 50/500 mg twice daily, titrated to glycemic response.
- Max Daily Dose: 100 mg Sitagliptin + 2000 mg Metformin (BNF).
- Renal Adjustment: Avoid if eGFR <45 mL/min (Metformin contraindicated <30 mL/min).
- Sitagliptin:
- Common: Nasopharyngitis, headache, dizziness.
- Rare: Acute pancreatitis, hypersensitivity reactions (e.g., angioedema) (BNF).
- Metformin:
- Common: Gastrointestinal disturbances (nausea, diarrhea, abdominal pain).
- Serious: Lactic acidosis (rare; risk factors include renal impairment, dehydration) (Lippincott).
Combination Therapy: Side effects reflect both components, with GI issues predominating.
- Renal Function:
- Monitor eGFR before and during treatment. Discontinue Metformin if eGFR <30 mL/min.
- Hepatic Impairment: Avoid in severe liver disease (Metformin risk).
- Pancreatitis: Discontinue Sitagliptin if severe abdominal pain occurs.
- Pregnancy:
- Sitagliptin: Limited data; insulin preferred.
- Metformin: BNF advises against use in pregnancy (Lange).
- Sitagliptin:
- ACE Inhibitors: Increased risk of angioedema.
- CYP3A4/5 Inducers (e.g., rifampicin): May reduce efficacy (Lippincott).
- Metformin:
- Cimetidine: Increases Metformin levels via renal tubular competition.
- Iodinated Contrast Media: Temporarily discontinue to prevent lactic acidosis (BNF).
- Alcohol: Potentiates lactic acidosis risk.
Combination: Monitor glucose levels with concomitant insulin/sulfonylureas.
- Sitagliptin:
- Generic: Sitagliptin.
- Brand Names:
- UK (BNF): Januvia®, Tesavel®.
- US: Januvia®.
- Sitagliptin/Metformin:
- Generic: Sitagliptin + Metformin.
- Brand Names:
- UK (BNF): Janumet®, Velmetia®.
- US: Janumet®.
