Current Australian guidelines recommend sulfonylureas as the usual initial second-line option, if treatment with metformin has failed to adequately control blood glucose levels.1,5,6
For most patients with type 2 diabetes, sulfonylureas:
- achieve similar reductions in HbA1c compared to other second-line oral agents (Table 1)1
- have long-term safety data which are supported by decades of clinical experience1, 3 and beneficial microvascular outcome data7, 8
- are cost-effective3 for the healthcare system and for some patients.1
Table 1: Expected decrease in HbA1c using different glucose-lowering medicinesa
|Medicine class||Expected decrease in HbA1c|
a HbA1c reduction is presented as percentage change from levels reported at baseline. Reported HbA1c reduction may be impacted by medicine class, dose, duration of diabetes and baseline glycaemia. Created using data from updated ADS guidelines.
b injectable agents
Not all sulfonylureas are the same
While comparable HbA1c-lowering effects are seen across the class,12-14 short-acting sulfonylureas (gliclazide and glipizide) have significant advantages and are generally preferred over long-acting sulfonylureas (glibenclamide and glimepiride), particularly because they are less likely to cause hypoglycaemia.1, 5, 15 In addition, it has been shown that people taking gliclazide can avoid escalation to insulin treatment for longer (14.5 years) than those taking the long-acting sulfonylurea glibenclamide (mean of 8 years).16
The lower risk of hypoglycaemia in patients taking gliclazide compared to glimepiride has been demonstrated across multiple studies. A 2015 systematic review and meta-analysis has also demonstrated a significantly lower risk of hypoglycaemia for gliclazide in comparison to other sulfonylureas (risk ratio 0.47, 95% CI 0.27–0.79, p = 0.004).13
There are currently limited data available comparing incidence of hypoglycaemia with gliclazide to other classes of oral blood glucose-lowering medicines. A recent systematic review and meta-analysis reported the risk of mild hypoglycaemia with gliclazide was not significantly different from other oral blood glucose-lowering medicines, including DPP-4 inhibitors (risk ratio 0.85, 95% CI 0.66–1.09, p = 0.20).13
Another study has reported incidence of non-severe hypoglycaemic events to be 2.2% for gliclazide users, compared to 1.8% for those using other oral blood glucose-lowering medicines (risk ratio 1.09, 95% CI 0.20–5.78).14 However, it was noted that there was a high heterogeneity across studies, and the definition and recording of hypoglycaemic events differed substantially between studies.14
Long-acting sulfonylureas have metabolites that are excreted renally,17 and should be avoided in older people, particularly those with deteriorating kidney function.15 Gliclazide and glipizide are metabolised by the liver, and are the sulfonylureas of choice for these patients.15
Short-acting sulfonylureas are comparable to long-acting sulfonylureas in their effects on weight. There are limited data on weight comparisons between gliclazide and other glucose-lowering medicines.