Alogliptin(AGLT),active ingredient of Alogliptin Benzoate(AGLT-BZ),is a new dipeptidyl peptidase-4(DPP-4)inhibitor for the treatment of type 2 diabetes.This study aimed to build a suitable method to determine the pote...Alogliptin(AGLT),active ingredient of Alogliptin Benzoate(AGLT-BZ),is a new dipeptidyl peptidase-4(DPP-4)inhibitor for the treatment of type 2 diabetes.This study aimed to build a suitable method to determine the potential related substances in AGLT-BZ bulk drug and tablets.Seven related substances in Alogliptin Benzoate substances were synthetized and identified by ^(1)H-NMR and ESI-MS.In addition,the impurities were detected by a gradient reverse-phase high performance liquid chromatography(RP-HPLC)with UV detection.The chromatographic system consisted of an Angilent Zobax SB-CN column(250×4.6 mm;5 μm).The mobile phase consisted of water/acetonitrile/trifluoroacetic acid 1900:100:1 v/v/v(solution A)and acetonitrile/water/trifluoroacetic acid 1900:100:1 v/v/v(solution B)using a gradient program at a flow rate of 1.0 ml/min with 278 nm detection and an injection volume of 20 ml.Additionally,selectivity,the limit of quantitation(LOQ)and limit of detection(LOD),linearity,accuracy,precision and robustness were determined.Linearity was good over the concentration range 50-1000 ng/ml and the coefficient of determination(R^(2))were 0.9991-0.9998.RSD% of the determination of precision were <2%(n=6).The method of RP-HPLC for the determination of impurities in AGLT-BZ was proved to be precise,accurate,robust and reliable.Three batches of self-made bulk drug and three dosages of commercial tablets were detected with this method.展开更多
Background: There are few clinical trials addressing the difference in pleiotropic effects among dipeptidyl peptidase (DPP)-4 inhibitors. We aimed to identify difference in effects on biochemical markers of inflammati...Background: There are few clinical trials addressing the difference in pleiotropic effects among dipeptidyl peptidase (DPP)-4 inhibitors. We aimed to identify difference in effects on biochemical markers of inflammation, oxidative stress, and atherosclerosis between two DPP-4 inhibitors in patients with type 2 diabetes. Methods: We prospectively observed twenty subjects with type 2 diabetes before and after a practical medication change from a treatment with pioglitazone and sitagliptin 50 mg to a combination tablet containing the same dose of pioglitazone and alogliptin 25mg, which was actually identical to switching from sitagliptin to alogliptin. After 3 months, changes from baseline in clinical data and various biochemical markers were evaluated. In particular, body mass index (BMI) and hemoglobin A1c (HbA1c) were additionally followed after 12 months for evaluation of chronic outcomes. Results: Among markers, serum levels of high molecular weight (HMW) adiponectin significantly increased from 6.9 ± 3.6 μg/ml to 8.2 ± 4.0 μg/ml (P = 0.0045). Although no clinical data changed after 3 months, significant improvements in HbA1c and BMI were observed after 12 months. Their rates of changes tended to inversely correlate with the increased percentages of serum HMW adiponectin levels during initial 3 months, but they did not reach statistical significance. Conclusions: In spite of pretreatment with pioglitazone, additional increase in serum HMW adiponectin levels was demonstrated after switching from sitagliptin to alogliptin. Given multiple favorable roles of adiponectin in metabolic and cardiovascular states, alogliptin, at least when combined with pioglitazone, would be beneficial in treatment of type 2 diabetes.展开更多
目的观察胰岛素泵强化治疗后阿格列汀对初诊2型糖尿病(T2DM)患者的效果及对白细胞介素-6(IL-6)的影响。方法T2DM患者80例,随机分为试验组、对照组,每组40例。对照组患者应用二甲双胍联合阿卡波糖降糖治疗,试验组患者应用阿格列汀联合阿...目的观察胰岛素泵强化治疗后阿格列汀对初诊2型糖尿病(T2DM)患者的效果及对白细胞介素-6(IL-6)的影响。方法T2DM患者80例,随机分为试验组、对照组,每组40例。对照组患者应用二甲双胍联合阿卡波糖降糖治疗,试验组患者应用阿格列汀联合阿卡波糖降糖治疗,观察12周。结果(1)治疗后,两组患者空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)水平均较治疗前明显下降(P<0.05),且试验组较对照组下降更明显(P<0.05);两组空腹及餐后2 h C肽水平较治疗前升高(P<0.05),但两组之间差异无统计学意义(P>0.05)。(2)治疗后试验组不良反应明显少于对照组,治疗依从性明显优于对照组,差异均有统计学意义(P<0.05)。(3)治疗后两组IL-6水平均下降,试验组下降更明显(P<0.05)。结论对于初诊的T2DM患者,短期胰岛素泵强化治疗后应用阿格列汀能够较好控制血糖,不良反应少,患者依从性好,同时阿格列汀可以降低炎症介质IL-6水平。展开更多
Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A represent...Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis. In addition to its peptidase activity, DPP-4 is known to be associated with immune stimulation, binding to and degradation of extracellular matrix, resistance to anti-cancer agents, and lipid accumulation. The liver expresses DPP-4 to a high degree, and recent accumulating data suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Furthermore, DPP-4 occurs in hepatic stem cells and plays a crucial role in hepatic regeneration. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor.展开更多
文摘Alogliptin(AGLT),active ingredient of Alogliptin Benzoate(AGLT-BZ),is a new dipeptidyl peptidase-4(DPP-4)inhibitor for the treatment of type 2 diabetes.This study aimed to build a suitable method to determine the potential related substances in AGLT-BZ bulk drug and tablets.Seven related substances in Alogliptin Benzoate substances were synthetized and identified by ^(1)H-NMR and ESI-MS.In addition,the impurities were detected by a gradient reverse-phase high performance liquid chromatography(RP-HPLC)with UV detection.The chromatographic system consisted of an Angilent Zobax SB-CN column(250×4.6 mm;5 μm).The mobile phase consisted of water/acetonitrile/trifluoroacetic acid 1900:100:1 v/v/v(solution A)and acetonitrile/water/trifluoroacetic acid 1900:100:1 v/v/v(solution B)using a gradient program at a flow rate of 1.0 ml/min with 278 nm detection and an injection volume of 20 ml.Additionally,selectivity,the limit of quantitation(LOQ)and limit of detection(LOD),linearity,accuracy,precision and robustness were determined.Linearity was good over the concentration range 50-1000 ng/ml and the coefficient of determination(R^(2))were 0.9991-0.9998.RSD% of the determination of precision were <2%(n=6).The method of RP-HPLC for the determination of impurities in AGLT-BZ was proved to be precise,accurate,robust and reliable.Three batches of self-made bulk drug and three dosages of commercial tablets were detected with this method.
文摘Background: There are few clinical trials addressing the difference in pleiotropic effects among dipeptidyl peptidase (DPP)-4 inhibitors. We aimed to identify difference in effects on biochemical markers of inflammation, oxidative stress, and atherosclerosis between two DPP-4 inhibitors in patients with type 2 diabetes. Methods: We prospectively observed twenty subjects with type 2 diabetes before and after a practical medication change from a treatment with pioglitazone and sitagliptin 50 mg to a combination tablet containing the same dose of pioglitazone and alogliptin 25mg, which was actually identical to switching from sitagliptin to alogliptin. After 3 months, changes from baseline in clinical data and various biochemical markers were evaluated. In particular, body mass index (BMI) and hemoglobin A1c (HbA1c) were additionally followed after 12 months for evaluation of chronic outcomes. Results: Among markers, serum levels of high molecular weight (HMW) adiponectin significantly increased from 6.9 ± 3.6 μg/ml to 8.2 ± 4.0 μg/ml (P = 0.0045). Although no clinical data changed after 3 months, significant improvements in HbA1c and BMI were observed after 12 months. Their rates of changes tended to inversely correlate with the increased percentages of serum HMW adiponectin levels during initial 3 months, but they did not reach statistical significance. Conclusions: In spite of pretreatment with pioglitazone, additional increase in serum HMW adiponectin levels was demonstrated after switching from sitagliptin to alogliptin. Given multiple favorable roles of adiponectin in metabolic and cardiovascular states, alogliptin, at least when combined with pioglitazone, would be beneficial in treatment of type 2 diabetes.
文摘目的观察胰岛素泵强化治疗后阿格列汀对初诊2型糖尿病(T2DM)患者的效果及对白细胞介素-6(IL-6)的影响。方法T2DM患者80例,随机分为试验组、对照组,每组40例。对照组患者应用二甲双胍联合阿卡波糖降糖治疗,试验组患者应用阿格列汀联合阿卡波糖降糖治疗,观察12周。结果(1)治疗后,两组患者空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)水平均较治疗前明显下降(P<0.05),且试验组较对照组下降更明显(P<0.05);两组空腹及餐后2 h C肽水平较治疗前升高(P<0.05),但两组之间差异无统计学意义(P>0.05)。(2)治疗后试验组不良反应明显少于对照组,治疗依从性明显优于对照组,差异均有统计学意义(P<0.05)。(3)治疗后两组IL-6水平均下降,试验组下降更明显(P<0.05)。结论对于初诊的T2DM患者,短期胰岛素泵强化治疗后应用阿格列汀能够较好控制血糖,不良反应少,患者依从性好,同时阿格列汀可以降低炎症介质IL-6水平。
文摘Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis. In addition to its peptidase activity, DPP-4 is known to be associated with immune stimulation, binding to and degradation of extracellular matrix, resistance to anti-cancer agents, and lipid accumulation. The liver expresses DPP-4 to a high degree, and recent accumulating data suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Furthermore, DPP-4 occurs in hepatic stem cells and plays a crucial role in hepatic regeneration. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor.
