薬理と治療

Abstract

Objectives Sitagliptin is an orally active, potent and selective dipeptidyl peptidase ︱4（DPP︱4）inhibitor for the treatment of type 2 diabetic patients. Sitagliptin acts through increasing incretin（GLP︱1 and GIP）hormone concentration, and reduces plasma glucose and HbA1c levels. Previously we reported that sitagliptin also reduces plasma triglyceride（TG）and remnant cholesterol（Jpn Pharmacol Ther 2011；39：217︱23）. Bezafibrate reduces mainly plasma TG and remnant cholesterol. Bezafibrate is reported to have a lowering effect of plasma glucose. However, there is little information about the effects of the combination therapy. In this study we investigated the effects of the combination therapy with sitagliptin and bezafibrate on glycemic control, lipids, hepatic function and renal function in type 2 diabetic patients. Methods Twenty︱two patients with type 2 diabetes were studied. All patients were treated with diet therapy only. Mean age was 64 years, mean BMI was 24.5 kg╱m2 and mean HbA1c （NGSP）was 7.2％ at the start of the study. Patients were treated with sitagliptin（50 mg╱day）for 3 months before the combination therapy. Bezafibrate（200 mg╱day）was added on. Patients were treated with the combination therapy with sitagliptin and bezafibrates over 7 months. HbA1c, plasma lipid levels, hepatic function and renal function were compared before and after the sitagliptin monotherapy or the combination therapy with sitagliptin and bezafibrate. Results Sitagliptin monotherapy significantly reduced HbA1c level （7.2±0.2％→6.3±0.2％,P＜0.001）. Add︱on therapy with bezafibrate significantly reduced HbA1c level（6.3±0.2％ →6.0±0.1％, P＜0.05）. Sitagliptin monotherapy significantly reduced TG level（275±16→143±8 mg╱dL, P＜0.001）. Add︱on therapy with bezafibrate significantly reduced TG level（143±8→108±5 mg╱dL, P＜0.001）. Sitagliptin monotherapy significantly reduced serum creatinin level（1.03±0.06→0.89±0.05 mg╱dL, P＜0.05）. Add︱on therapy with bezafibrate significantly reduced creatinin level（0.89±0.05→0.83 ±0.04 mg╱dL, P＜0.05）. Hepatic functions（AST, ALT, γ︱GTP）tended to decrease after the monotherapy and the combination therapy, but these changes were not statistically significant. Conclusion It is concluded that the combination therapy with sitagliptin and bezafibrate is more effective to reduce HbA1c as well as plasma TG than sitagliptin monotherapy in type 2 diabetic patients. Furthermore, the combination therapy showed the improvement of serum creatinin level. This finding suggests that the combination therapy protects and improves diabetic nephropathy.