Long-Term Efficacy And Safety Of Add-On Therapy Of Sitagliptin To A Very Small Dose Of Glimepiride Versus A Small Dose Of Glimepiride Over Eighteen Months

Background: In patients associated with type 2 diabetes mellitus, sulfonylureas (SUs) are being prescribed less frequently, and in smaller doses, to avoid hypoglycemia and body weight gain. On the other hand, since dipeptidyl peptidase-4 (DPP-4) inhibitors only infrequently induce hypoglycemia and weight gain, more than 60% or 70% of Japanese patients associated with type 2 diabetes mellitus are currently being treated with DPP-4 inhibitors. However, the longterm effects of DPP-4 inhibitors on glycemic control and beta-cell function have not been thoroughly elucidated.Methods: The present study was designed to compare the long-term efficacy and safety of a daily administration of 50 mg sitagliptin added to a very/ small dose of glimepiride, SUs, of 1.1 mg (SIT group), versus a small dose of glimepiride added by 1 mg to its basal dosage, i.e., 2.1 mg (SU group) up to 18 months in Japanese patients with type 2 diabetes mellitus. Sixty patients, aged 20 to 75 years with hemoglobin A1c (HbA1c) between 7.4% and 9.0% on glimepiride with or without metformin. were randomized into two groups. If the target (HbA1c <= 6.9% or fasting plasma glucose level <= 130 mg/dL) was not achieved, sitagliptin or glimepiride, respectively, was increased.Results: After 18 months, HbA1c had significantly decreased to 7.1-7.2% in both groups (P < 0.01). Plasma levels of insulin and proinsulin remained unchanged during the study. However, the proinsulin/insulin ratio was significantly lower after 6 months and thereafter only in the SU group. Homeostasis model assessment-beta cell (HOMA-beta) demonstrated a significant augmentation at some points during the study in both groups. No severe hypoglycemic episodes or body weight gain were seen in either group.Conclusions: Add-on therapy of 50 mg of sitagliptin to a very small dose of glimepiride at 1.1 to 1.2 mg/day, or a small dose of glimepiride at 2.1 mg/day, proved effective for improving or maintaining glycemic control without deterioration of( )beta-cell function over 18 months.