2021A Question 13
List the major classes of oral hypoglycaemic drugs and provide an example of each class. Briefly outline their mechanisms of action and major side effects.
Examiner Report
57.4% of candidates achieved a pass in this question.
To pass this question it was expected candidates would:
- List several classes of oral hypoglycaemics and provide an example for each
- Include the mechanism of action for each drug class
- List at least 1 major side effect for each class
Either a table or a simple list were acceptable ways to format the answer. Credit was awarded for including major perioperative implications for the main classes of drugs, but this was not necessary to pass. Marks were not awarded for the discussion of insulin pharmacology.
Common problems included:
- A lack of breadth (only including 2 or 3 classes of drugs)
- Lack of depth (such as very basic mechanisms, or complete omission of mechanisms)
- Confusing the mechanism of action between classes and for misclassifying drug examples
- Adverse effects were often vague, or incorrect (in particular, regarding risk of hypoglycaemia)
Model Answer
| Class | Example | Mechanism of action | Side effects |
|---|---|---|---|
| Biguanide | Metformin | - ↓ Hepatic glucose production (by glycogenolysis, gluconeogenesis) - ↑ Insulin sensitivity |
- Diarrhoea - Renal impairment: ↑ risk if dehydrated, iodine contrast, other nephrotoxins. - Rare lactic acidosis (inhibit complex 1 of electron transport chain) |
| Sulfonylurea | Gliclazide | - Inhibit K+-ATP channel → Depolarisation → Activate VDCC → ↑ ICF Ca2+ → Exocytosis of insulin vesicles ↑ insulin release - Requires functioning pancreas |
- Risk hypoglycaemia peri-op - Long-term “burnout”, β-cell failure, insulin dependence |
| Apical SGLT2 inhibitor | Dapagliflozin | - ↓ Glucose reabsorption → Glycosuria - Limit plasma glucose to 10mM - Weight loss |
- UTI - Osmotic diuresis - Occult DKA-like state |
| a-glucosidase inhibitor | Acarbose | - ↓ Glucose reabsorption - Weight loss |
Osmotic diarrhoea, abdominal pain |
| DPP4 inhibitor | Sitagliptin | - ↓ Breakdown of incretins GLP-1 and GIP - Requires functioning pancreas |
- Minimal - Nausea - Cold-like symptoms - Photosensitivity |
| Thiazolidenedione PPARγ agonists | Rosiglitazone | ↓ Insulin resistance | Weight gain, oedema, hepatitis |