Makindo Medical Notes

Key point: DPP-4 inhibitors such as saxagliptin (Onglyza) generally do not cause hypoglycaemia unless combined with sulfonylureas or insulin. 🚫🍬 However, there is an important safety concern: gliptins have been linked with acute pancreatitis. 🩺🔥 Saxagliptin is an orally active inhibitor of DPP-4, used with diet, exercise, and often in combination with other oral agents or insulin to improve glycaemic control in type 2 diabetes mellitus (T2DM).

📘 About

• Always check the BNF for latest prescribing advice.
• Licensed for adults with T2DM, usually when metformin alone is insufficient.
• May be combined with metformin, sulfonylureas, thiazolidinediones, SGLT2 inhibitors, or insulin.

⚙️ Mode of Action

• Inhibits the enzyme dipeptidyl peptidase-4 (DPP-4).
• This slows degradation of incretin hormones (GLP-1, GIP) → enhanced insulin secretion (glucose-dependent) and suppressed glucagon secretion.
• Result: Lower blood glucose without major risk of hypoglycaemia or weight gain.

💊 Indication & Dose

• Type 2 Diabetes Mellitus: 5 mg once daily PO (can be given with or without food).

🔄 Interactions

• See BNF for full list.
• Caution if combined with sulfonylurea or insulin → risk of hypoglycaemia (dose adjustment of these agents may be required).
• Potential interactions with strong CYP3A4/5 inhibitors (e.g., ketoconazole, clarithromycin) → may increase saxagliptin exposure.

⚠️ Cautions

• Renal impairment: Reduce to 2.5 mg OD if eGFR < 50 mL/min/1.73m².
• Monitor for symptoms of pancreatitis (severe abdominal pain radiating to the back).
• Use with caution in hepatic impairment.

🚫 Contraindications

• History of pancreatitis.
• Moderate to severe heart failure (NYHA class III–IV) due to trial evidence of increased risk of hospitalisation for HF with saxagliptin.

💥 Side Effects

• Common: Upper respiratory symptoms (sore throat, cough), headache, GI upset (abdominal pain, dyspepsia/GERD).
• Skin: Rash, pruritus.
• Rare but important: Acute pancreatitis, joint pain, heart failure exacerbation.

📚 References

• BNF – Saxagliptin
• Scirica BM et al. SAVOR-TIMI 53 Trial: Saxagliptin and cardiovascular outcomes in T2DM (NEJM 2013).

📝 Revisions

• September 2025 – Expanded UK prescribing advice, cardiovascular safety notes, and teaching points.