Sulfonylureas have long been used for the treatment of type 2 diabetes and were the first oral anti-hyperglycemic agents to be introduced into clinical practice. They are still widely used and are first- or second-line drugs if the hemoglobin A1c (HbA1c) target is not achieved after metformin monotherapy [1,2]. Sulfonylureas stimulate insulin secretion by inhibiting the potassium flux through ATP-dependent potassium channels (K_ATP) in pancreatic β-cells and are most effective in patients who have had diabetes for less than 5 years, and who have residual endogenous insulin production [3]. These drugs have potent and rapid hypoglycemic effects; however, these effects are short-lived and HbA1c eventually increases over time [4]. In addition, there are some safety issues, including hypoglycemia, weight gain, and possibly risk of cardiovascular disease [5].

In this issue, Min et al. [6] investigated the clinical characteristics of patients who are dependent on sulfonylurea treatment for adequate glycemic control. The authors retrospectively selected 19 patients whose HbA1c was maintained below 7.5% with a small dose of sulfonylurea (glimepiride ≤2 mg/day or equivalent dose). The HbA1c level increased after discontinuing the sulfonylurea, but fell again after resuming treatment. The average age of the patients was 67±11 years and there was no gender difference. The mean body mass index was 25.1±3.1 kg/m² and 73% of the patients had a first-degree family history of type 2 diabetes. In addition, although the patients had relatively long durations of diabetes (18±10 years), β-cell function was preserved; fasting C-peptide level was 3.9±2.6 ng/mL.

To date, there has been much effort to determine who best will respond to a specific anti-hyperglycemic agent and which drug is the best option for certain type 2 diabetes patients for optimal glycemic control. Despite these efforts, selecting the best anti-hyperglycemic agent for an individual with type 2 diabetes is still complicated. Furthermore, there is no way to determine who will show good glycemic control after discontinuing sulfonylureas. Although Min et al. [6] did not report the proportion of sulfonylurea-dependent patients among all patients receiving sulfonylurea treatment, and did not compare clinical characteristics between sulfonylurea-dependent patients and sulfonylurea-independent patients, there is arguably a population of type 2 diabetics who can best benefit from sulfonylurea treatment for optimal glycemic control. Future studies need to characterize patients with type 2 diabetes who show a good response to sulfonylureas and are dependent on sulfonylurea treatment for adequate glycemic control.