AIM: To assess the effects of sitagliptin and nateglinide on lipid metabolism. METHODS: In a parallel group comparative open trial, patients with type 2 diabetes mellitus under treatment at the Japanese Red Cross Medi...AIM: To assess the effects of sitagliptin and nateglinide on lipid metabolism. METHODS: In a parallel group comparative open trial, patients with type 2 diabetes mellitus under treatment at the Japanese Red Cross Medical Center were randomly assigned to receive either sitagliptin (50 mg once daily) or nateglinide (90 mg three times daily before meals). Eligible patients met the following criteria: age ≥ 20 years; hemoglobin A 1c (HbA 1c ) > 6.5% despite diet and exercise; HbA 1c between 6.5% and 8.0%; fasting glucose < 7.77 mmol/L; diet and exercise therapy for more than 3 mo; and ability to read and understand the information for written informed consent. Exclusion criteria were contraindications to sitagliptin, contraindications to nateglinide, pregnancy or possible pregnancy, and severe liver/renal failure. Patients who were considered to be unsuitable by the attending physician for other reasons were also excluded. Blood samples were collected at one and three hours after intake of a test meal. The primary outcome measure was the area under the curve (AUC) of apolipoprotein (Apo) B48 at three hours postprandially. RESULTS: Twenty patients were randomly assigned to the sitagliptin group and sixteen patients were randomized to the nateglinide group. All 36 patients took the medication as directed by the physician in both groups, and they all were analyzed. Apart from antidiabetic drugs, there was no difference between the two groups with respect to the frequency of combined use of lipid-lowering, antihypertensive, and/or antiplatelet drugs. The doses of these medications were maintained during 12 wk of treatment. Detailed dietary advice, together with adequate exercise therapy, was given to the patients so that other factors apart from the two test drugs were similar in the two groups. There were no significant differences of the baseline characteristics between the two groups, except for body mass index (the sitagliptin group: 25.14 ± 3.05 kg/m 2 ; the nateglinide group: 21.39 ± 2.24 kg/m 2 ). Fasting levels of HbA 1c , glycated albumin, 1.5-anhydroglucitol, and blood glucose, as well as the blood glucose levels at one and three hours postprandially, improved in both groups after 12 wk of treatment, and there were no significant differences between the two groups. However, the glucagon level at one hour postprandially (P = 0.040) and the diastolic blood pressure (P<0.01) only showed a significant decrease in the sitagliptin group. In the nateglinide group, there was no significant change in the AUC of Apo B48, the glucagon level at one hour postprandially, the fasting triglyceride level, or the diastolic blood pressure. Body weight was unchanged in both groups. However, the AUC of Apo B48 at three hours postprandially showed a significant decrease in the sitagliptin group from 2.48 ± 0.11 at baseline to 1.94 ± 0.78 g/L per hour after 12 wk (P=0.019). The fasting triglyceride level also decreased significantly in the sitagliptin group (P = 0.035). With regard to lipid-related markers other than Apo B48 and fasting triglycerides, no significant changes were observed with respect to Apo A1, Apo B, or Apo C3 in either group. No adverse events occurred in either group. CONCLUSION: Sitagliptin significantly improves some lipid parameters while having a comparable effect on blood glucose to nateglinide. A large-scale prospective study of sitagliptin therapy is warranted.展开更多
The stability of three forms of nateglinide, especially S-form and H-form, was determined. S-form was a new crystal structure1 of nateglinide. Three forms of nateglinide were treated in different conditions, such as...The stability of three forms of nateglinide, especially S-form and H-form, was determined. S-form was a new crystal structure1 of nateglinide. Three forms of nateglinide were treated in different conditions, such as in various temperatures, humidity, light and so on. Analysis of their crystal structures was performed by X-ray powder diffraction ( XRD ) and their particle shapes were observed with scanning electron microscope ( SEM ). The results indicated that the stability of S-form of nateglinide is the best among the three forms and their particle shapes are quite difference. S-form is the sheet structure of layer upon layer, H-form looks like a hank of silk lines and B-form is the clubbed shape.展开更多
The aim of this study was to characterize the provesicle formulation of nateglinide(NTG)to facilitate the development of a novel controlled release system of NTG with improved efficacy and oral bioavailability compare...The aim of this study was to characterize the provesicle formulation of nateglinide(NTG)to facilitate the development of a novel controlled release system of NTG with improved efficacy and oral bioavailability compared to the currently marketed NTG formulation(Glinate^(™)60).NTG provesicles were prepared by a slurry method using the non-ionic surfactant,Span 60(SP),and cholesterol(CH)as vesicle forming agents and maltodextrin as a coated carrier.Multilamellar niosomes with narrow size distribution were shown to be successfully prepared by means of dynamic laser scattering(DLS)and field emission scanning electron microscopy(FESEM).The absence of drug-excipient interactions was confirmed by Fourier transform infrared spectroscopy(FT-IR),differential scanning calorimetry(DSC)and X-ray diffraction(XRD)studies.In vitro release of NTG in different dissolution media was improved compared to pure drug.A goat intestinal permeation study revealed that the provesicular formulation(F4)with an SP:CH ratio of 5:5 gave higher cumulative amount of drug permeated at 48 h compared to Glinate^(™)60 and control.A pharmacodynamic study in streptozotocin-induced diabetic rats confirmed that formulation F4 significantly(P<0.05)reduced blood glucose levels in comparison to Glinate 60.Overall the results show that controlled release NTG provesicles offer a useful and promising oral delivery system for the treatment of type Ⅱ diabetes.展开更多
The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabet...The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients. We present a patient with steroid-induced diabetes whose blood glucose levels were ameliorated by the use of the DPP-4 inhibitor, showing that the DPP-4 inhibitors may be an effective and safe oral anti-diabetic drug for steroid-induced diabetes.展开更多
文摘AIM: To assess the effects of sitagliptin and nateglinide on lipid metabolism. METHODS: In a parallel group comparative open trial, patients with type 2 diabetes mellitus under treatment at the Japanese Red Cross Medical Center were randomly assigned to receive either sitagliptin (50 mg once daily) or nateglinide (90 mg three times daily before meals). Eligible patients met the following criteria: age ≥ 20 years; hemoglobin A 1c (HbA 1c ) > 6.5% despite diet and exercise; HbA 1c between 6.5% and 8.0%; fasting glucose < 7.77 mmol/L; diet and exercise therapy for more than 3 mo; and ability to read and understand the information for written informed consent. Exclusion criteria were contraindications to sitagliptin, contraindications to nateglinide, pregnancy or possible pregnancy, and severe liver/renal failure. Patients who were considered to be unsuitable by the attending physician for other reasons were also excluded. Blood samples were collected at one and three hours after intake of a test meal. The primary outcome measure was the area under the curve (AUC) of apolipoprotein (Apo) B48 at three hours postprandially. RESULTS: Twenty patients were randomly assigned to the sitagliptin group and sixteen patients were randomized to the nateglinide group. All 36 patients took the medication as directed by the physician in both groups, and they all were analyzed. Apart from antidiabetic drugs, there was no difference between the two groups with respect to the frequency of combined use of lipid-lowering, antihypertensive, and/or antiplatelet drugs. The doses of these medications were maintained during 12 wk of treatment. Detailed dietary advice, together with adequate exercise therapy, was given to the patients so that other factors apart from the two test drugs were similar in the two groups. There were no significant differences of the baseline characteristics between the two groups, except for body mass index (the sitagliptin group: 25.14 ± 3.05 kg/m 2 ; the nateglinide group: 21.39 ± 2.24 kg/m 2 ). Fasting levels of HbA 1c , glycated albumin, 1.5-anhydroglucitol, and blood glucose, as well as the blood glucose levels at one and three hours postprandially, improved in both groups after 12 wk of treatment, and there were no significant differences between the two groups. However, the glucagon level at one hour postprandially (P = 0.040) and the diastolic blood pressure (P<0.01) only showed a significant decrease in the sitagliptin group. In the nateglinide group, there was no significant change in the AUC of Apo B48, the glucagon level at one hour postprandially, the fasting triglyceride level, or the diastolic blood pressure. Body weight was unchanged in both groups. However, the AUC of Apo B48 at three hours postprandially showed a significant decrease in the sitagliptin group from 2.48 ± 0.11 at baseline to 1.94 ± 0.78 g/L per hour after 12 wk (P=0.019). The fasting triglyceride level also decreased significantly in the sitagliptin group (P = 0.035). With regard to lipid-related markers other than Apo B48 and fasting triglycerides, no significant changes were observed with respect to Apo A1, Apo B, or Apo C3 in either group. No adverse events occurred in either group. CONCLUSION: Sitagliptin significantly improves some lipid parameters while having a comparable effect on blood glucose to nateglinide. A large-scale prospective study of sitagliptin therapy is warranted.
基金The authors gratefully acknowledge the support of the Natural Science Foundation of Jiangsu Province(BK2001111)Jiangsu Province Key Lab of Drug Delivery System(DDS200101)the Key Material Lab of Nanjing Normal University.
文摘The stability of three forms of nateglinide, especially S-form and H-form, was determined. S-form was a new crystal structure1 of nateglinide. Three forms of nateglinide were treated in different conditions, such as in various temperatures, humidity, light and so on. Analysis of their crystal structures was performed by X-ray powder diffraction ( XRD ) and their particle shapes were observed with scanning electron microscope ( SEM ). The results indicated that the stability of S-form of nateglinide is the best among the three forms and their particle shapes are quite difference. S-form is the sheet structure of layer upon layer, H-form looks like a hank of silk lines and B-form is the clubbed shape.
基金This work was financially supported by the All India Council of Technical Education(AICTE)India(Grant No.KLECOP/QIP/2010).
文摘The aim of this study was to characterize the provesicle formulation of nateglinide(NTG)to facilitate the development of a novel controlled release system of NTG with improved efficacy and oral bioavailability compared to the currently marketed NTG formulation(Glinate^(™)60).NTG provesicles were prepared by a slurry method using the non-ionic surfactant,Span 60(SP),and cholesterol(CH)as vesicle forming agents and maltodextrin as a coated carrier.Multilamellar niosomes with narrow size distribution were shown to be successfully prepared by means of dynamic laser scattering(DLS)and field emission scanning electron microscopy(FESEM).The absence of drug-excipient interactions was confirmed by Fourier transform infrared spectroscopy(FT-IR),differential scanning calorimetry(DSC)and X-ray diffraction(XRD)studies.In vitro release of NTG in different dissolution media was improved compared to pure drug.A goat intestinal permeation study revealed that the provesicular formulation(F4)with an SP:CH ratio of 5:5 gave higher cumulative amount of drug permeated at 48 h compared to Glinate^(™)60 and control.A pharmacodynamic study in streptozotocin-induced diabetic rats confirmed that formulation F4 significantly(P<0.05)reduced blood glucose levels in comparison to Glinate 60.Overall the results show that controlled release NTG provesicles offer a useful and promising oral delivery system for the treatment of type Ⅱ diabetes.
文摘The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients. We present a patient with steroid-induced diabetes whose blood glucose levels were ameliorated by the use of the DPP-4 inhibitor, showing that the DPP-4 inhibitors may be an effective and safe oral anti-diabetic drug for steroid-induced diabetes.
