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Masahiko Gosho
Hypoglycemia is the most important complication of antidiabetic medications. Most patients with diabetes mellitus take multiple medications. In this study, we explored clinical drug-drug interactions that result in hypoglycemia by analyzing the Japanese Adverse Drug Event Report (JADER) database. The primary outcome was the report of hypoglycemia. The Norén and Gosho methods, which quantitatively measure the discrepancy between the observed and expected number of adverse events under the combination of 2 drugs, were used as the criteria for detecting drug-drug interactions...
May 15, 2018: Journal of Clinical Pharmacology
Kanta Fujimoto, Yui Shibayama, Eriko Yamaguchi, Sachiko Honjo, Akihiro Hamasaki, Yoshiyuki Hamamoto
BACKGROUND: Glucose excursions and hypoglycemia are associated with cardiovascular complications. However, no studies have evaluated glucose excursions and the frequency of hypoglycemia in patients treated with mitiglinide/voglibose versus glimepiride as add-on to dipeptidyl peptidase-4 inhibitor therapy. METHODS: This cross-over trial included 20 patients with type 2 diabetes. After initiating vildagliptin 100 mg, patients were randomly assigned to receive mitiglinide 10 mg/voglibose 0...
March 1, 2018: Journal of Diabetes
Kenichi Tanaka, Yosuke Okada, Hiroko Mori, Keiichi Torimoto, Tadashi Arao, Yoshiya Tanaka
One adverse effect of methylprednisolone (MP) pulse therapy is an acute dose-dependent increase in the blood glucose level. Five patients with thyroid ophthalmopathy but normal glucose tolerance received MP pulse therapy (3 cycles, 3 days/week) and were assessed by continuous glucose monitoring. Steroid therapy increased the mean sensor glucose level, and all patients developed steroid-induced diabetes. The patients were treated alternately with mitiglinide (30 mg/day) and repaglinide (1.5 mg/day) during the second or third MP pulse therapy...
January 1, 2018: Internal Medicine
Hongliang Li, Hye Won Kim, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Amy L Firth, Il-Whan Choi, Il Yong Han, Dae-Sung Lee, Mi-Jin Yim, Won Sun Park
AIMS: The vasorelaxant effects of the anti-diabetic drug, mitiglinide in phenylephrine (Phe)-pre-contracted aortic rings were examined. MATERIALS AND METHODS: Arterial tone measurement was performed in aortic smooth muscle cells. KEY FINDINGS: Mitiglinide dose-dependently induced vasorelaxation. Application of the large-conductance Ca(2+)-activated K(+) (BKCa) channel blocker paxilline, inwardly rectifying K(+) (Kir) channel blocker Ba(2+), and ATP-sensitive K(+) (KATP) channel blocker glibenclamide did not affect the vasorelaxant effect of mitiglinide...
November 1, 2017: Life Sciences
Kenji Akahane, Kazuma Ojima, Ayaka Yokoyama, Toshihiro Inoue, Sumiyoshi Kiguchi, Satoshi Tatemichi, Hiroo Takeda, Yohsuke Imai
We examined the effects of combining the rapid insulin secretagogue, mitiglinide, with various oral hypoglycaemic drugs including biguanides, pioglitazone, α-glucosidase inhibitors, and sodium-glucose co-transporter 2 inhibitors in a rat model of type 2 diabetes. The oral glucose tolerance test (OGTT) using glucose, sucrose, or a liquid meal was used to compare the effects of mitiglinide with those of the four oral hypoglycaemic drugs and examine their combined effects on blood glucose levels and insulin secretion in the rat model...
July 26, 2017: Clinical and Experimental Pharmacology & Physiology
Shijia Liu, Peidong Chen, Yang Zhao, Guoliang Dai, Bingting Sun, Yao Wang, Anwei Ding, Wenzheng Ju
BACKGROUND: Mitiglinide is a widely used agent for diabetic treatment. We established a pharmacokinetic-pharmacodynamic (PK-PD) model to illustrate the relationship between mitiglinide plasma concentration and its glucose lowering effects in healthy volunteers. METHODS: The volunteers participated in the test after the administration of a single dose of 10 mg mitiglinide. The drug concentration in Plasma and the values of glucose levels were determined by LC-MS/MS assay and hexokinase method...
July 4, 2017: BMC Pharmacology & Toxicology
Kenji Akahane, Kazuma Ojima, Ayaka Yokoyama, Toshihiro Inoue, Sumiyoshi Kiguchi, Satoshi Tatemichi, Hiroo Takeda, Mamoru Kobayashi
We compared the individual effects of mitiglinide and glibenclamide administered in combination with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin on plasma DPP-IV activity and blood glucose levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes (STZ-NA rats). We examined the inhibitory activity of mitiglinide and glibenclamide as well as their combination with sitagliptin on plasma DPP-IV activity in STZ-NA rats. The oral glucose tolerance test (OGTT) was used to compare effects of mitiglinide, glibenclamide, and their combination with sitagliptin on blood glucose levels in STZ-NA rats...
July 2017: Drug Research
Zhengyu Han, Rui Wang, Guoxian Gu, Xiu-Qin Dong, Xumu Zhang
Asymmetric hydrogenation of various 3-substituted maleic anhydrides catalyzed by Rh/bisphosphine-thiourea (ZhaoPhos) under mild conditions was successfully developed. A wide range of 3-alkyl and 3-aryl maleic anhydrides were hydrogenated well to provide the desired products 3-substituted succinic anhydrides in one hour with excellent results (full conversions, up to 99% yield, 99% ee, 3000 TON). Importantly, we developed a creative and efficient synthetic route to construct the key intermediate of the hypoglycemic drug mitiglinide through our catalytic system...
April 11, 2017: Chemical Communications: Chem Comm
Tadashi Arao, Yosuke Okada, Keiichi Torimoto, Kei Sugai, Takashi Otsuka, Akira Kurozumi, Yoshiya Tanaka
We analyzed the effects of 100 mg/day sitagliptin and a switch to mitiglinide calcium hydrate/voglibose compound tablets (MIT/VOG) in patients with type 2 diabetes mellitus (T2DM) treated with 50 mg/day sitagliptin. Five patients with T2DM treated with 50 mg/day sitagliptin and hemoglobin A1c (HbA1c) of ≥6.5% were switched to MIT/VOG, or the dose of sitagliptin was increased to 100 mg/day. The effects of the changes in therapy were compared in a crossover fashion by continuous glucose monitoring. The primary endpoint was mean amplitude of glycemic excursions (MAGE), and the secondary end points were 24-hour mean blood glucose level and mean blood glucose level from 0:00 a...
2017: Journal of UOEH
Takashi Tomita, Hidekazu Goto, Kenji Sumiya, Tadashi Yoshida, Katsuya Tanaka, Kenzo Kudo, Yukinao Kohda
The aim of this study was to examine the effect of food thickener on the pharmacodynamics of mitiglinide (MGN), a drug belonging to a class of rapid-acting insulin secretagogues. First, MGN tablets were coated by immersion in a xanthan gum-based food-thickening agent. This treatment was shown to delay disintegration rates of MGN tablets in vitro. The pharmacodynamics of MGN after ingestion of a single oral dose of an MGN tablet, with or without food thickener immersion, were then examined in an open-label crossover study comprising 5 healthy participants...
June 2017: Dysphagia
Noriko Ihana-Sugiyama, Ritsuko Yamamoto-Honda, Takehiro Sugiyama, Tetsuro Tsujimoto, Masafumi Kakei, Mitsuhiko Noda
BACKGROUND Although the efficacy of combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) has been shown, which OHAs are the most efficient remains unclear. MATERIAL AND METHODS Five patients with type 2 diabetes were enrolled and treated with insulin degludec and metformin as a basal therapy. The patients were randomized in a cross-over fashion to receive a combination of mitiglinide (10 mg) and voglibose (0.2 mg) (M+V) 3 times daily or linagliptin (5 mg) (L) once daily for 8 weeks...
February 28, 2017: Medical Science Monitor Basic Research
Atsuo Tahara, Toshiyuki Takasu, Masanori Yokono, Masakazu Imamura, Eiji Kurosaki
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...
February 2016: Archives of Pharmacal Research
Yumie Takeshita, Toshinari Takamura, Yuki Kita, Akiko Takazakura, Ken-Ichiro Kato, Yuki Isobe, Shuichi Kaneko
PURPOSE: We determined the feasibility of substituting sitagliptin or mitiglinide for bolus insulin injection therapy in patients with type 2 diabetes. METHODS: 60 patients with type 2 diabetes were enrolled and randomized to switch from mealtime dosing of a rapid-acting insulin analog to either sitagliptin or mitiglinide for 16 weeks. RESULTS: Body weight, body mass index, and waist circumference decreased significantly in both groups at the end of the study...
2015: BMJ Open Diabetes Research & Care
Angela M Abbatecola, Mario Bo, Fabio Armellini, Ferdinando D'Amico, Giovambattista Desideri, Paolo Falaschi, Antonio Greco, Gianbattista Guerrini, Fabrizia Lattanzio, Clelia Volpe, Giuseppe Paolisso
BACKGROUND: There is growing evidence that tight glycemic control may be more harmful than beneficial in older persons with Type 2 diabetes (T2DM). It remains controversial if tight glycemic control (lower glycated hemoglobin A1c (A1c)) is associated with functional impairments in older frail patients with T2DM. We explored associations between A1c and losses in Activities of Daily Living (ADLs) in diabetic nursing home (NH) patients and tested for differences according to anti-diabetic treatment: diet, anti-diabetic oral drug (AOD), insulin, combined insulin+AOD...
November 2015: Metabolism: Clinical and Experimental
Khaldun Mohammad Al Azzam, Ermafatiha Muhammad
PURPOSE: The present study is aimed to study the host-guest inclusion complexation of the naturally occurring cyclodextrins (CDs), namely; (α-CD,β-CD, and γ-CD) with mitiglinide (MIT). METHODS: Host-guest inclusion complexation was simulated using semi-empirical PM3 method. RESULTS: The obtained results clearly indicate that the complexes formed are energetically favored in the presence of γ-CD (Ecomp = -17.884 kcal/mol) of the optimal configurations of (1:1) MIT/γ-CD inclusion complexes...
June 2015: Advanced Pharmaceutical Bulletin
S Tani, K Nagao, A Hirayama
PURPOSE: The purpose of this study was to compare the effects of mitiglinide/voglibose fixed-dose combination and glimepiride on low-density lipoprotein (LDL)-heterogeneity in type-2 diabetic patients with unstable glycemic control after treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors. METHODS: This was an open-label pilot study in which type-2 diabetic patients were randomly assigned to the mitiglinide/voglibose (fixed-dose combination of mitiglinide 10 mg and voglibose 0...
February 2016: Drug Research
Jong-Ha Baek, Sang-Man Jin, Kohei Kaku, Jin-Ah Jung, Jung-Ryul Kim, Jae-Wook Ko, Min-Ji Kim, Soo-Youn Lee, Woo-seong Huh, Jae Hyeon Kim
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...
June 2015: Expert Opinion on Pharmacotherapy
Yoshio Nagai
Many patients with type 2 diabetes mellitus(T2DM) do not achieve satisfactory glycemic control by monotherapy alone, and often require multiple oral hypoglycemic agents (OHAs). Combining OHAs with complementary mechanisms of action is fundamental to the management of T2DM. Fixed-dose combination therapy(FDC) offers a method of simplifying complex regimens. Efficacy and tolerability appear to be similar between FDC and treatment with individual agents. In addition, FDC can enhance adherence and improved adherence may result in improved glycemic control...
March 2015: Nihon Rinsho. Japanese Journal of Clinical Medicine
Takaaki Murakami, Takuo Nambu, Tomoko Kato, Yuki Matsuda, Shin Yonemitsu, Seiji Muro, Shogo Oki
The combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor and a long-acting insulin analogue is widely used in clinical practice. However, some patients fail to achieve lower postprandial hyperglycemia. Mitiglinide, a short-acting insulinotropic sulfonylurea receptor ligand, is effective for postprandial hyperglycemia. Recently, it has been reported that the combination therapy of mitiglinide with a DPP-4 inhibitor could improve glycemic control. However, the efficacy of those under long-acting insulin analogue therapy remains to be investigated...
April 2015: Tohoku Journal of Experimental Medicine
Miao Chen, Cheng Hu, Weiping Jia
Glinides, including repaglinide, nateglinide and mitiglinide, are a type of fasting insulin secretagogue that could help to mimic early-phase insulin release, thus providing improved control of the postprandial glucose levels. Glinides stimulate insulin secretion by inhibiting ATP-sensitive potassium channels in the pancreatic β-cell membrane. Although glinides have been widely used clinically and display excellent safety and efficacy, the response to glinides varies among individuals, which is partially due to genetic factors involved in drug absorption, distribution, metabolism and targeting...
January 2015: Pharmacogenomics
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