Sulfonylureas
Second-line oral hypoglycaemic agents for Type 2 Diabetes Mellitus (T2DM). Often used in combination with metformin or as monotherapy when metformin is contraindicated or not tolerated.
Mechanism of Action
- Stimulate pancreatic β-cells to secrete insulin, independent of glucose concentration
- Result: ↑ circulating insulin levels regardless of glycaemic state
- No effect on insulin sensitivity or hepatic glucose output
Efficacy
- Reduces HbA1c by 0.6–1.5% (approx. 7–16 mmol/mol)
- Rapid onset of action – useful in newly diagnosed T2DM with marked hyperglycaemia
Safety Profile and Limitations
Benefits:
- Long-standing clinical use with well-characterised safety
- Proven efficacy in improving glycaemic control
Limitations:
- Hypoglycaemia (dose- and agent-dependent)
- More common with longer-acting sulfonylureas (e.g. glibenclamide)
- ↑ Risk in elderly, frail, or those with renal/hepatic impairment
- Weight gain: Typically 1–3 kg
- Durability: May lose effectiveness over time due to β-cell burnout
Use with caution in:
- Older adults (due to hypoglycaemia risk)
- Renal or hepatic dysfunction (dose adjustment or alternative preferred)
PBS Status (Australia)
- Subsidised under the Pharmaceutical Benefits Scheme for:
- Monotherapy
- Dual/triple therapy in T2DM management
Key Clinical Trials
- UKPDS:
- Sulfonylurea therapy (chlorpropamide, glibenclamide) reduced microvascular complications
- Neutral effect on cardiovascular outcomes in early phases
- ADVANCE Trial (using gliclazide MR):
- Confirmed microvascular benefit in intensive glucose control arms
- Did not significantly reduce macrovascular outcomes
Common Sulfonylureas in Australia
| Medication | Brand Name | Available Doses | Starting Dose | Usual Maintenance Dose | Maximum Dose |
|---|---|---|---|---|---|
| Glimepiride | Amaryl | 1 mg, 2 mg, 3 mg, 4 mg | 1 mg once daily | 1–4 mg once daily | 8 mg daily |
| Gliclazide (IR) | Diamicron | 80 mg | 40–80 mg once or twice daily | 40–320 mg/day in divided doses | 320 mg daily |
| Gliclazide (MR) | Diamicron MR | 30 mg, 60 mg, 120 mg | 30 mg once daily | 30–120 mg once daily | 120 mg daily |
| Glipizide | Minidiab | 2.5 mg, 5 mg | 2.5–5 mg once daily | 2.5–20 mg/day (single or divided doses) | 40 mg daily |
| Glibenclamide (Glyburide) | Daonil | 2.5 mg, 5 mg | 2.5–5 mg daily | 2.5–15 mg/day in divided doses | 20 mg daily |