Withdrawal of sulfonylureas from patients with type 2 diabetes receiving long-term sulfonylurea and insulin combination therapy results in deterioration of glycemic control: a randomized controlled trial

Background: The benefit of sulfonylureas (SUs) to patients with type 2 diabetes mellitus receiving long-term insulin treatment is unclear. This study evaluated glycemic control and beta-cell function after SU withdrawal in these patients. Methods: In this 8-week randomized controlled study, patients with type 2 diabetes who had been treated with insulin for at least 3 years plus moderate to high doses of SUs were randomly assigned to withdrawal (n=16) or continuation (n=16) of SUs. Clinical characteristics, glycemic control, hypoglycemic events, and insulin secretion, including homeostasis model assessment of beta-cell function (HOMA-B) score, C-peptide concentration, and Matsuda index, were evaluated at baseline and after 2 and 8 weeks. Results: Thirty patients (16 in the SU withdrawal group and 14 in the SU continuation group) completed the study. Median duration of diabetes was 17 (range 5-40) years. Baseline clinical characteristics, glycemic control, and HOMA-B were similar in the two groups, but the mean fasting C-peptide concentration was higher in the SU withdrawal group. After 8 weeks, the SU withdrawal group showed a significant increase in mean glycosylated hemoglobin levels from 7.8%+/- 0.5% (62 +/- 5 mmol/mol) to 8.6%+/- 1.2% (71 +/- 13 mmol/mol; P=0.002), whereas the SU continuation group showed a slight but not significant increase from 7.7%+/- 0.5% (61 +/- 5 mmol/mol) to 7.9%+/- 1.2% (63 +/- 13 mmol/mol; P=0.37). Insulin secretion, as measured by C-peptide and HOMA-B, decreased by 18% and 36%, respectively, in the SU withdrawal group. Hypoglycemic events were significantly more frequent in the SU continuation group whereas body weight did not change significantly in either group. Conclusion: Withdrawal of SU from patients with type 2 diabetes receiving long-term combination treatment with SU and insulin resulted in deterioration of glycemic control and insulin secretion.