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薬理と治療
Abstract
Objective In 2010, vildagliptin became available in Japan. Vildagliptin is an orally active andselective dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of type 2 diabeticpatients. Vildagliptin acts through increasing incretin(GLP-1 and GIP)hormone concentration,and reduces postprandial plasma glucose and HbA1c levels. In addition, DPP-4 inhibitorwas reported to reduce postprandial plasma triglyceride(TG)level. Remnant lipoproteinswhich underlie hypertriglyceridemia are known to be atherogenic as well as LDL. In addition,DPP-4 inhibitor was reported to reduce blood pressures. There is little information aboutthe effects of vildagliptin therapy on postprandial levels of plasma TG and remnant cholesteroland blood pressures in Japan. Thus, in this study the effects were estimated in patientswhose type 2 diabetes was not optically controlled.Methods Thirty five patients with type 2 diabetes and baseline HbA1c(JDS)≧6.2% to≦7.5% were studied. Mean age was 59 years, and mean BMI was 27.1 kg/m2. Twenty twopatients were treated with vildagliptin monotherapy(100 mg/day). Thirteen patients weretreated with glimepiride(0.5 mg/day n=7, 1 mg/day n=6)at least for 3 months before thestudy entry, and vildagliptin(100 mg/day)was added on. Patients were treated with monotherapyor add-on therapy with vildagliptin over 6 months. HbA1c and postprandial levels ofplasma glucose, TG and remnant cholesterol were compared before and after mototherapy oradd-on therapy. HbA1c was measured by high-performance liquid chromatography. Plasmaremnant cholesterol was determined as RLP-cholesterol(normal range<5.2 mg/dL)by themethod of Nakajima et al. Blood pressures were also compared in the patients. Twenty onepatients were treated with ARB(n=9), Ca blocker(n=3)or combination therapy with ARBand Ca blocker(n=9)before the study entry and during the study.Results Overall, mono- and add-on therapy with vildagliptin significantly reduced HbA1c level(7.0±0.1%→6.2±0.1%, p<0.001), postprandial levels of plasma glucose(170±9→136±8 mg/dL, p<0.001), plasma TG(194±18→118±6 mg/dL, p<0.001)and remnant cholesterol(7.8±0.9→4.3±0.3 mg/dL, p<0.001). There was no significant change in LDL cholesteroland HDL cholesterol levels before and after the treatment with vildagliptin. In vildagliptinmonotherapy group(n=22), it significantly reduced HbA1c level(6.8±0.1%→6.1±0.1%, p<0.001), postprandial levels of plasma glucose(153±10→133±9 mg/dL, p<0.001),plasma TG(186±22→114±8 mg/dL, p<0.001)and remnant cholesterol(7.8±1.5→3.8±0.3mg/dL, p<0.001). In vildagliptin add-on therapy group(n=13), it significantly reducedHbA1c level(7.3±0.2%→6.4±0.1%, p<0.001), postprandial levels of plasma glucose(198±13→141±10 mg/dL, p<0.001), plasma TG(208±33→123±8 mg/dL, p<0.001)and remnantcholesterol(7.7±1.1→5.0±0.4 mg/dL, p<0.001).Overall, mono- and add-on therapy with vildagliptin significantly reduced systolic bloodpressure (138±2 mmHg→126±2 mmHg, p<0.001) and diastolic blood pressure (82±2mmHg→76±2 mmHg, p<0.01).Body weight was not significantly changed, and no adverse reactions such as hypoglycemiawere observed over the study period.Conclusion It is concluded that mono- or add-on therapy with vildagliptin is effective toreduce HbA1c and postprandial glucose as well as postprandial TG and remnant cholesterolin Japanese type 2 diabetic patients. In addition, it reduces blood pressures. Vildagliptin maybe useful for the protection of macroangiopathy and microangiopathy in type 2 diabeticpatients.
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