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Kohei Kaku - One of the best experts on this subject based on the ideXlab platform.
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efficacy of Mitiglinide and sitagliptin alone or in combination on postprandial excursion and glycemic variability assessed by continuous glucose monitoring a post hoc analysis with single day treatment
Expert Opinion on Pharmacotherapy, 2015Co-Authors: Jongha Baek, Jin Ah Jung, Kohei Kaku, Jungryul Kim, Sooyoun Lee, Wooseong Huh, Sangman Jin, Minji Kim, Jae Hyeon KimAbstract:Objective: To compare the efficacy of Mitiglinide and sitagliptin, alone or in combination, on postprandial excursion and glycemic variability assessed by continuous glucose monitoring (CGM) in a single-day treatment setting.Methods: This was a post hoc analysis of a randomized crossover study comparing the efficacy of sitagliptin, Mitiglinide and the combination of these two drugs. Twenty-four hour CGM was performed before and after a single-day treatment with each drug alone or in combination.Results: Mean glucose levels were decreased in all groups. The average of three postprandial glucose excursions AUC (average of all three 4-h postprandial periods throughout the day) (AUCpp-average) decreased in the Mitiglinide and combination treatment groups, but not in the sitagliptin group. The lowering effect on AUCpp-average was greater in patients given Mitiglinide (–47 mg/dl, p < 0.001) or combination treatment (–66 mg/dl, p < 0.001) compared with sitagliptin alone (–18 mg/dl). The reduction in mean amplitu...
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long term effects of Mitiglinide in japanese diabetics inadequately controlled with dpp 4 inhibitor or biguanide monotherapy
Diabetes Therapy, 2014Co-Authors: Kohei Kaku, Nobuya Inagaki, Naoki KobayashiAbstract:The goal of treatment in diabetes is to control hyperglycemia to near-normal glucose levels, which is important to prevent the progression of microvascular and macrovascular complications. Mitiglinide is a rapid- and short-acting insulinotropic sulfonylurea receptor ligand that is known to improve postprandial hyperglycemia in patients with type 2 diabetes. The aim of this study was to investigate the long-term efficacy and safety of Mitiglinide in Japanese type 2 diabetic patients inadequately controlled by dipeptidyl peptidase-4 (DPP-4) inhibitor or biguanide monotherapy. In patients with type 2 diabetes mellitus (T2DM) receiving a stable monotherapy regimen with a DPP-4 inhibitor or biguanide added to dietary therapy, an additional 10 mg Mitiglinide was administered for 52 weeks. The efficacy end points were postprandial plasma glucose (PPG) (30 min, 1 h, 2 h), postprandial insulin (30 min, 1 h, 2 h), insulinogenic index, 1,5-anhydroglucitol (1,5-AG), glycated hemoglobin (HbA1c), and fasting plasma glucose. The safety end points included the incidence and types of adverse events and adverse drug reactions. A total of 136 patients with T2DM were eligible for enrollment in this study and received Mitiglinide. The average HbA1c before the start of Mitiglinide administration (baseline) was 7.47% in the DPP-4 inhibitor combined treatment group (DPP-4 inhibitor CTG) and 7.50% in the biguanide combined treatment group (biguanide CTG), and the 2 h PPG was 248.1 and 243.3 mg/dL, respectively. Following the addition of Mitiglinide to the treatment regimen for 52 weeks, the early postprandial decrease in insulin secretion improved and PPG improved in both the DPP-4 inhibitor CTG and biguanide CTG. At final evaluation, the HbA1c <7.0% achievement rate was 57.4% in the DPP-4 inhibitor CTG and 29.2% in the biguanide CTG. The incidence of hypoglycemia in the DPP-4 inhibitor CTG and biguanide CTG was 3.0% (2/67 patients) and 2.9% (2/69 patients), respectively. The hypoglycemic symptoms were mild in all cases. Combination therapy with Mitiglinide and DPP-4 inhibitors or biguanides improved glycemic control over the long term without increasing risks to safety due to events such as hypoglycemia, and this is a clinically promising therapeutic strategy in T2DM.
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additive postprandial glucose lowering effects of Mitiglinide and sitagliptin in patients with type 2 diabetes mellitus
Advances in Therapy, 2013Co-Authors: Jin Ah Jung, Kohei Kaku, Jae Hyeon Kim, Jungryul Kim, Sooyoun Lee, Wooseong HuhAbstract:The aim of this research was to compare the pharmacodynamics of the combination of Mitiglinide and sitagliptin to that of each agent alone in Korean patients with type 2 diabetes mellitus (T2DM). Patients with T2DM received Mitiglinide alone, sitagliptin alone, or both drugs together in randomized sequence. A meal tolerance test (MTT) was conducted for each group, and plasma concentrations of glucose, insulin, C-peptide, glucagon, and intact glucagon-like peptide-1, and dipeptidyl peptidase-4 activity were measured from 2 h before breakfast through 4 h after breakfast on day 0 (pretreatment) and day 1 (posttreatment) of each treatment period. Integrated values of these pharmacodynamic variables were analyzed for changes from pretreatment to posttreatment and for differences between the three treatment groups. Twenty-six patients with glycated hemoglobin A1c level of 7.4% ± 0.6%, fasting plasma glucose concentration of 141 ± 22 mg/dL, postprandial plasma glucose (PPG) concentration of 264 ± 48 mg/dL 1 h after the MTT, and diabetes duration of 3.0 ± 3.1 years (mean ± SD) were included in the study. Compared with Mitiglinide or sitagliptin alone, the combination treatment lowered PPG additively (P < 0.001 vs. Mitiglinide or sitagliptin alone) and the insulin secretory response (P = 0.03 vs. Mitiglinide or sitagliptin alone). The integrated insulin concentrations changed significantly from before to after treatment (P < 0.01), but the change did not differ between the combination and Mitiglinide groups. The insulinogenic index increased significantly after the combination treatment (P < 0.001 vs. Mitiglinide or sitagliptin alone). The combination of Mitiglinide and sitagliptin was generally well tolerated, with no hypoglycemic events. The combination of Mitiglinide and sitagliptin did not trigger hypoglycemia and controlled postprandial glucose excursion more effectively compared with either drug alone.
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effect of Mitiglinide on glycemic control over 52 weeks in japanese type 2 diabetic patients insufficiently controlled with pioglitazone monotherapy
Endocrine Journal, 2009Co-Authors: Kohei Kaku, Shunichi Tanaka, Hideki Origasa, Masatoshi Kikuchi, Yasuo AkanumaAbstract:This study was performed to examine the efficacy and safety of the rapid- and short-acting insulinotropic SUR ligand Mitiglinide given as add-on therapy for 52 weeks in type 2 diabetic patients whose blood glucose was insufficiently controlled by pioglitazone monotherapy. Type 2 diabetic patients aged ≥ 20 years with postprandial plasma glucose (PPG1 or 2) ≥ 200 mg/dL and glycated hemoglobin (HbA1C) 6.5–<9.0% despite receiving pioglitazone 15–45 mg/day were additionally treated with concomitant Mitiglinide 10 mg tid p.o. for a total treatment period of 52 weeks. In 171 patients recruited, HbA1C was significantly reduced from 7.64 ± 0.77% at baseline to 6.84 ± 0.73%, 6.64 ± 0.64%, 6.67 ± 0.57% and 6.81 ± 0.65% at weeks 16, 28, 40, and 52, respectively. Over half the patients achieved HbA1C target of <7.0%, and one third <6.5%. Significant reductions in fasting plasma glucose (FPG) and PPG 1 and 2 hours after a meal versus baseline were noted at all time-points evaluated. The most frequently noted adverse reactions were hypoglycemic symptoms, weight gain, and peripheral edema (all mild). In type 2 diabetic patients combination therapy with Mitiglinide and pioglitazone exerted significant long-term improvements in HbA1C, FPG, and PPG and was well tolerated. This drug combination therapy is a promising means of alleviating insufficient pancreatic insulin secretion and insulin resistance.
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addition of Mitiglinide to pioglitazone monotherapy improves overall glycemic control in japanese patients with type 2 diabetes a randomized double blind trial
Endocrine Journal, 2009Co-Authors: Kohei Kaku, Shunichi Tanaka, Hideki Origasa, Masatoshi Kikuchi, Yasuo AkanumaAbstract:A 16-week, multicenter, randomized, double blind, parallel-group study was performed to examine whether additional administration of Mitiglinide improves glycemic control in Japanese type 2 diabetic patients who are insufficiently controlled by pioglitazone monotherapy. Japanese adult type 2 diabetic patients were at first treated with diet plus pioglitazone 15-30 mg/day for 4 weeks then randomized to receive additional Mitiglinide 5 or 10 mg or placebo tid for a further 16 weeks. In all, 381 patients were randomized. At final evaluation, glycated hemoglobin (HbA(1C)) was reduced by (mean +/- SD) -0.02 +/- 0.60% in the pioglitazone monotherapy group and by -0.45 +/- 0.77% and -0.67 +/- 0.59% in the Mitiglinide 5 and 10 mg combination groups, respectively (both p<0.001 vs. pioglitazone monotherapy group). The percentage of patients who achieved HbA(1C) targets was significantly (p<0.001) higher in the Mitiglinide combination groups than in the pioglitazone monotherapy group. Significant improvements in fasting plasma glucose and postprandial plasma glucose were noted in the Mitiglinide combination groups versus the pioglitazone monotherapy group. No increase in adverse events was noted when Mitiglinide was administered concomitantly with pioglitazone monotherapy. Hypoglycemic adverse events were infrequently and similarly observed in all three groups. Body weight gain and edema presented no clinical problem. HbA(1C) was significantly improved in the Mitiglinide combination groups compared with the pioglitazone monotherapy group, and significantly more patients achieved HbA(1C) targets. Therefore Mitiglinide effectively improves glycemic control in type 2 diabetic patients who are inadequately controlled by pioglitazone monotherapy.
Gangyi Yang - One of the best experts on this subject based on the ideXlab platform.
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effect of Mitiglinide calcium on fasting plasma fibroblast growth factor 21 level in patients with newly diagnosed type 2 diabetes mellitus
Chinese Journal of Endocrinology and Metabolism, 2012Co-Authors: Yingying Fan, Gangyi Yang, Li Ling, L I Zhiyong, Yong Liao, Chunrui Cheng, Shiguo Tang, L I Shengbing, Yi WangAbstract:Eighty-two newly-diagnosed type 2 diabetic patients with poor glycemic control were treated by Mitiglinide calcium for 16 weeks.Plasma fibroblast growth factor-21 ( FGF-21 ) level were evaluated.The relationship of plasma FGF-21 levels with body mass index,body fat,waist-to-hip ratio,lipid,blood glucose,HbA1c,and free fatty-acid were analyzed.Plasma FGF-21 was decreased significantly by treatment with Mitiglinide calcium in type 2 diabetic patients,and it may play a role in the pathogenesis of type 2 diabetes mellitus. Key words: Mitiglinide calcium; Diabetes mellitus, type 2; Fibroblast growth factor-21
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efficacy and safety of Mitiglinide versus nateglinide in newly diagnose patients with type 2 diabetes mellitus a randomized double blind trial
Diabetes Obesity and Metabolism, 2012Co-Authors: Mengliu Yang, X Yan, H Guo, H Pan, Hua Liu, Y Liao, Gangyi YangAbstract:This study was performed to examine the efficacy and safety of Mitiglinide in type 2 diabetes patients (T2DM). Enrolled patients had received treatment with diet and exercise in the previous 3 months with glycosylated haemoglobin (HbA1c) 7-10%, and were randomized to receive Mitiglinide (n = 111, 5-20 mg/meal) or nateglinide (n = 114,60-120 mg/meal) for 16 weeks. Primary and secondary efficacy endpoints were assessed by the changes in HbA1c, fasting blood glucose (FBG) and postprandial glucose (PBG) levels. The baseline HbA1c value was 8.2 and 8.3% in both groups. At the end of study, the reduction of HbA1c values from baseline by Mitiglinide was slightly more than that by nateglinide (-1.11% vs. -0.76%), but not statically significant (p = 0.06). Final FBG and PBG were comparable for the two treatments. There were 2.8% subjects treated with nateglinide who had hypoglycaemic episodes, but none in the Mitiglinide treatment group. The results indicate that Mitiglinide and nateglinide had similar effects on FBG, PBG and HbA1c in T2DM patients after the 16-week treatments.
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Mitiglinide treatment may decreases plasma fibroblast growth factor 21 levels in individuals with new onset t2dm
Cytokine, 2012Co-Authors: Bo Wang, Mengliu Yang, Gangyi Yang, Yong Liao, Guenther BodenAbstract:Abstract Fibroblast growth factor 21 (FGF-21) has been identified as a potent metabolic regulator. Despite the importance of FGF-21 in the regulation of glucose, lipid and energy homeostasis, much less is known about the effect of common anti-diabetic treatment on the plasma levels of FGF-21. The aim of our study was to measure its plasma levels in patients with new-onset type 2 diabetes mellitus (nT2DM) and healthy subjects, and to assess the changes of its circulating levels after pharmacological interventions. One hundred and eleven patients with nT2DM, and 87 gender-, age- and body mass index (BMI)-matched normal glucose tolerance (NGT) controls participated in the study. The patients with nT2DM were treated with Mitiglinide for 16 weeks. Biochemical parameters, plasma FGF-21 and insulin levels were measured by commercial ELISA or RIA kits pre- and post-treatment with Mitiglinide. Fasting plasma FGF-21 levels were higher in the nT2DM group than in controls (3.21 ± 1.37 vs. 1.52 ± 0.36 μg/L, P P
Yasuo Akanuma - One of the best experts on this subject based on the ideXlab platform.
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effect of Mitiglinide on glycemic control over 52 weeks in japanese type 2 diabetic patients insufficiently controlled with pioglitazone monotherapy
Endocrine Journal, 2009Co-Authors: Kohei Kaku, Shunichi Tanaka, Hideki Origasa, Masatoshi Kikuchi, Yasuo AkanumaAbstract:This study was performed to examine the efficacy and safety of the rapid- and short-acting insulinotropic SUR ligand Mitiglinide given as add-on therapy for 52 weeks in type 2 diabetic patients whose blood glucose was insufficiently controlled by pioglitazone monotherapy. Type 2 diabetic patients aged ≥ 20 years with postprandial plasma glucose (PPG1 or 2) ≥ 200 mg/dL and glycated hemoglobin (HbA1C) 6.5–<9.0% despite receiving pioglitazone 15–45 mg/day were additionally treated with concomitant Mitiglinide 10 mg tid p.o. for a total treatment period of 52 weeks. In 171 patients recruited, HbA1C was significantly reduced from 7.64 ± 0.77% at baseline to 6.84 ± 0.73%, 6.64 ± 0.64%, 6.67 ± 0.57% and 6.81 ± 0.65% at weeks 16, 28, 40, and 52, respectively. Over half the patients achieved HbA1C target of <7.0%, and one third <6.5%. Significant reductions in fasting plasma glucose (FPG) and PPG 1 and 2 hours after a meal versus baseline were noted at all time-points evaluated. The most frequently noted adverse reactions were hypoglycemic symptoms, weight gain, and peripheral edema (all mild). In type 2 diabetic patients combination therapy with Mitiglinide and pioglitazone exerted significant long-term improvements in HbA1C, FPG, and PPG and was well tolerated. This drug combination therapy is a promising means of alleviating insufficient pancreatic insulin secretion and insulin resistance.
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addition of Mitiglinide to pioglitazone monotherapy improves overall glycemic control in japanese patients with type 2 diabetes a randomized double blind trial
Endocrine Journal, 2009Co-Authors: Kohei Kaku, Shunichi Tanaka, Hideki Origasa, Masatoshi Kikuchi, Yasuo AkanumaAbstract:A 16-week, multicenter, randomized, double blind, parallel-group study was performed to examine whether additional administration of Mitiglinide improves glycemic control in Japanese type 2 diabetic patients who are insufficiently controlled by pioglitazone monotherapy. Japanese adult type 2 diabetic patients were at first treated with diet plus pioglitazone 15-30 mg/day for 4 weeks then randomized to receive additional Mitiglinide 5 or 10 mg or placebo tid for a further 16 weeks. In all, 381 patients were randomized. At final evaluation, glycated hemoglobin (HbA(1C)) was reduced by (mean +/- SD) -0.02 +/- 0.60% in the pioglitazone monotherapy group and by -0.45 +/- 0.77% and -0.67 +/- 0.59% in the Mitiglinide 5 and 10 mg combination groups, respectively (both p<0.001 vs. pioglitazone monotherapy group). The percentage of patients who achieved HbA(1C) targets was significantly (p<0.001) higher in the Mitiglinide combination groups than in the pioglitazone monotherapy group. Significant improvements in fasting plasma glucose and postprandial plasma glucose were noted in the Mitiglinide combination groups versus the pioglitazone monotherapy group. No increase in adverse events was noted when Mitiglinide was administered concomitantly with pioglitazone monotherapy. Hypoglycemic adverse events were infrequently and similarly observed in all three groups. Body weight gain and edema presented no clinical problem. HbA(1C) was significantly improved in the Mitiglinide combination groups compared with the pioglitazone monotherapy group, and significantly more patients achieved HbA(1C) targets. Therefore Mitiglinide effectively improves glycemic control in type 2 diabetic patients who are inadequately controlled by pioglitazone monotherapy.
Yuri Ono - One of the best experts on this subject based on the ideXlab platform.
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glycemic metabolic responses to identical meal tolerance tests at breakfast lunch and dinner in japanese patients with type 2 diabetes mellitus treated with a dipeptidyl peptidase 4 inhibitor and the effects of adding a Mitiglinide voglibose fixed dose combination
Expert Opinion on Pharmacotherapy, 2014Co-Authors: Yuri Ono, Hikaru Kamoshima, Akinobu Nakamura, Hiroshi NomotoAbstract:Background: The effects of the Mitiglinide/voglibose fixed-dose combination on postprandial glycemic/metabolic responses in patients with type 2 diabetes mellitus (T2DM) treated with dipeptidyl peptidase-4 (DPP-4) inhibitors are unknown.Methods: Twelve T2DM patients treated with a DPP-4 inhibitor underwent identical meal tolerance tests (MTTs) at breakfast, lunch and dinner, before and 2 – 3 weeks after treatment with a fixed-dose combination of Mitiglinide 10 mg and voglibose 0.2 mg (combination). Patients were randomized in a cross-over fashion to administer the combination either three-times-daily before each meal or twice-daily before breakfast and dinner. Glycemic/metabolic responses were evaluated at 0, 30, 60 and 120 min in each MTT.Results: Three-times-daily administration of the combination significantly suppressed postprandial hyperglycemia after each meal, particularly after lunch and dinner. Active glucagon-like peptide-1 levels increased significantly after each meal, as did early-phase insul...
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the glycemic metabolic responses to meal tolerance tests at breakfast lunch and dinner and effects of the Mitiglinide voglibose fixed dose combination on postprandial profiles in japanese patients with type 2 diabetes mellitus
Expert Opinion on Pharmacotherapy, 2014Co-Authors: Yuri Ono, Kyu Yong Cho, Akinobu Nakamura, Hiroshi NomotoAbstract:Background: Meal tolerance tests (MTTs) are usually conducted at breakfast after overnight fasting in type 2 diabetes mellitus (T2DM) patients, but differences in postprandial glycemic responses between meals have been reported. Objective: We conducted MTTs at breakfast, lunch, and dinner to examine the effects of a fixed combination of 10 mg Mitiglinide/0.2 mg voglibose (the combination) on glycemic/metabolic responses to meals during the day in T2DM patients. MTTs with unified meals were conducted in 11 T2DM patients before and after 4 weeks of treatment with the combination administered thrice daily before meals. Glycemic/metabolic profiles measured before and at 30, 60, and 120 min after each meal were compared between each meal and between the baseline and treatment periods. Results and conclusion: The combination significantly reduced postprandial hyperglycemia after each meal. Postprandial AUC0 – 120 min for insulin significantly decreased after lunch and dinner compared with after breakfast, while...
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Mitiglinide voglibose fixed dose combination improves postprandial glycemic excursions in japanese patients with type 2 diabetes mellitus
Expert Opinion on Pharmacotherapy, 2013Co-Authors: Yuri Ono, Hiraku Kameda, Kyu Yong ChoAbstract:Objective: We examined the effects of a fixed-dose combination of 10 mg Mitiglinide and 0.2 mg voglibose on postprandial glycemic excursions in Japanese type 2 diabetes mellitus (T2DM) patients. Research design and methods: After a 2-week baseline period, 11 T2DM patients were treated with Mitiglinide alone for 2 weeks and with the Mitiglinide/voglibose combination for 6 weeks. Main outcome measures: Self-monitoring of blood glucose (SMBG) at home before and after unified meals, metabolic parameters during meal tolerance tests, and overall glycemic control parameters. Results: Postprandial glycemic excursions after all three meals, as assessed by SMBG, were significantly lower in the combination period than in the baseline period, and after lunch and dinner in the combination period than in the Mitiglinide period. The meal tolerance test confirmed that the magnitude of postprandial hyperglycemia was significantly lower, with significantly greater early-phase serum insulin secretion and sustained GLP-1 pro...
Atsuo Tahara - One of the best experts on this subject based on the ideXlab platform.
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Effects of the combination of SGLT2 selective inhibitor ipragliflozin and various antidiabetic drugs in type 2 diabetic mice
Archives of pharmacal research, 2015Co-Authors: Atsuo Tahara, Masanori Yokono, Toshiyuki Takasu, Masakazu Imamura, Eiji KurosakiAbstract:The sodium-glucose cotransporter 2 (SGLT2) is responsible for most glucose reabsorption in the kidney and has been proposed as a novel therapeutic target for the treatment of type 2 diabetes. In the present study, the combinatory effects of SGLT2 selective inhibitor ipragliflozin and various antidiabetic drugs in high-fat diet and streptozotocin-nicotinamide-induced type 2 diabetic mice were investigated. Ipragliflozin dose-dependently increased urinary glucose excretion and improved glucose tolerance. In addition, each antidiabetic drug (Mitiglinide, glibenclamide, sitagliptin, insulin, metformin, voglibose, or rosiglitazone) also significantly improved glucose tolerance without affecting urinary glucose excretion. Combination treatment of ipragliflozin with each antidiabetic drug additively improved glucose tolerance. In these experiments, ipragliflozin-induced increases in urinary glucose excretion were not influenced by combination treatment with antidiabetic drugs. Further, ipragliflozin did not affect antidiabetic drug-induced insulinotropic action (Mitiglinide and glibenclamide), increases in plasma glucagon-like peptide-1 and insulin levels via inhibition of dipeptidyl peptidase 4 activity (sitagliptin), increases in plasma insulin level (insulin), decreases in hepatic phosphoenolpyruvate carboxykinase activity (metformin), inhibition of small intestinal disaccharidase activity (voglibose), or improvement of impaired insulin secretion (rosiglitazone). These results suggest that combination treatment of ipragliflozin with various antidiabetic drugs additively enhances the improvement in glucose tolerance without affecting each drug’s unique pharmacological effects. Ipragliflozin may therefore be expected to be effective when administered as part of a combination regimen in the treatment of type 2 diabetes.
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effects of antidiabetic drugs in high fat diet and streptozotocin nicotinamide induced type 2 diabetic mice
European Journal of Pharmacology, 2011Co-Authors: Atsuo Tahara, Akiko Matsuyamayokono, Masayuki ShibasakiAbstract:Abstract Based on previously established methods, we developed an easily available type 2 diabetic mouse model that exhibits obesity and insulin resistance. We investigated the effects of several antidiabetic drugs on this new model, which was induced by a high-fat diet in combination with streptozotocin and nicotinamide injection. Male ICR mice were fed a high-fat diet (45% of calories as fat) for 3 weeks and then intraperitoneally administered with nicotinamide (1000 mg/kg) and streptozotocin (150 mg/kg). These diabetic mice exhibited hyperglycemia and glucose intolerance as a result of the loss of early-phase insulin secretion. The mice also developed significant insulin resistance, hyperlipidemia and obesity. A single dose of Mitiglinide, glibenclamide, sitagliptin, insulin, metformin and voglibose significantly improved glucose tolerance during a liquid meal tolerance test. Repeated administration of sitagliptin and rosiglitazone also improved hyperglycemia and insulin resistance. These results demonstrate that a high-fat diet combined with nicotinamide and streptozotocin injection induces a diabetic mouse model that replicates the metabolic characteristics of human type 2 diabetes. This diabetic model, which exhibits impaired insulin secretion, glucose intolerance, insulin resistance, and obesity, may be suitable to evaluate antidiabetic agents for the treatment of type 2 diabetes.