Nocturnal Hypoglycemia in Individuals with Type 2 Diabetes Receiving Concomitant Use of DPP-4 Inhibitors and Sulfonylureas: An Analysis Using Continuous Glucose Monitoring

Background: Hypoglycemia has harmful effects on chronic complications of diabetes, and when it occurs at night, it is often asymptomatic. When oral hypoglycemic medications with different mechanisms of action that promote insulin secretion are used in combination in the individual with type 2 diabetes, hypoglycemia may occasionally occur. Therefore, we investigated blood glucose fluctuations with a focus on nocturnal hypoglycemia in the individuals with type 2 diabetes undergoing concomitant use of these medicines using continuous glucose monitoring (CGM) as a retrospective observational study. Methods: The participants consisted of 59 Japanese individuals with type 2 diabetes treated with a DPP-4 inhibitor and glimepiride (N = 30) or gliclazide (N = 29). Clinical factors including HbA1c were not significantly different between these groups. Blood glucose was monitored using CGM for 10 days. Hypoglycemia was defined as monitoring glucose less than 54 mg/dL for at least 15 min. Results: Asymptomatic nocturnal [from midnight to 6:00 AM (6 h)] hypoglycemia was observed more frequently in the glimepiride group (43.3%) than the gliclazide group (6.9%), p = 0.002. All hypoglycemia was unrecognized. Logistic regression analyses indicated that nocturnal hypoglycemia was significantly associated with concomitant use of a DPP-4 inhibitor and glimepiride. Conclusions: Among individuals with type 2 diabetes who had relatively good glycemic control, asymptomatic nocturnal hypoglycemia occurred more frequently in the group treated with a DPP-4 inhibitor and glimepiride than that treated with a DPP-4 inhibitor and gliclazide. Even when HbA1c levels were comparable, the use of CGM that could monitor nocturnal glucose fluctuation clearly identified this difference.