💊 DPP-4 Inhibitors
Drug Class & Overview
DPP-4 inhibitors (gliptins) are oral antihyperglycaemic agents used in the management of Type 2 Diabetes Mellitus, often as an add-on therapy when metformin alone is insufficient or not tolerated.
Mechanism of Action
DPP-4 inhibitors prevent the breakdown of incretin hormones (GLP-1 and GIP) by inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4). This increases the levels of active incretins, which enhance glucose-dependent insulin secretion and suppress glucagon secretion.
Key Indications
DPP-4 inhibitors are indicated for Type 2 Diabetes Mellitus, typically as a second-line agent in combination with metformin, a sulfonylurea, or a thiazolidinedione. They can also be used as monotherapy in patients for whom metformin is inappropriate or not tolerated.
Contraindications
Contraindications include Type 1 Diabetes Mellitus and diabetic ketoacidosis. Caution is advised in patients with a history of pancreatitis, as there have been rare reports of pancreatitis associated with their use. Dose adjustment may be required in renal impairment depending on the specific agent.
Adverse Effects
Common adverse effects are generally mild and include nasopharyngitis, headache, and gastrointestinal upset. Rare but serious adverse effects include pancreatitis, severe hypersensitivity reactions (e.g., angioedema), and bullous pemphigoid. They generally have a low risk of hypoglycaemia when used as monotherapy.
Monitoring
Renal function should be monitored periodically, as some DPP-4 inhibitors require dose adjustment in renal impairment. HbA1c is monitored every 3-6 months to assess glycaemic control. Patients should be advised to report symptoms suggestive of pancreatitis.
Prescribing Safety (OSCE)
When prescribing DPP-4 inhibitors, check for renal impairment to ensure appropriate dosing. Counsel patients on the symptoms of pancreatitis (severe, persistent abdominal pain) and advise them to seek immediate medical attention if these occur. They are generally well-tolerated with few significant drug interactions.
MLA High-Yield Notes
DPP-4 inhibitors are weight-neutral and have a low risk of hypoglycaemia, making them a good option for many patients. Remember their mechanism involves enhancing endogenous incretins. Be aware of the rare association with pancreatitis. Examples include sitagliptin, vildagliptin, saxagliptin, and linagliptin.
Common SBA Themes
SBAs often test the mechanism of action (incretin enhancement) and their low risk of hypoglycaemia compared to sulfonylureas. Questions may also focus on their place in therapy (add-on to metformin) and the rare but serious adverse effect of pancreatitis.
References
- BNF (British National Formulary)
- NICE Guideline NG28: Type 2 diabetes in adults: management
- MHRA Drug Safety Update: DPP-4 inhibitors and risk of pancreatitis