Glufast (mitiglinide) / Takeda, Kissei - LARVOL DELTA

Structural similarity-based search for glinides exhibiting cis- and trans-inhibitory activity toward uric acid transporter 1. (PubMed, Mol Pharmacol) - "Three glinides (nateglinide, mitiglinide, and repaglinide) all inhibited urate uptake by HEK-hURAT1 cells concentration-dependently (IC50: nateglinide, 39 μM; mitiglinide, 63 μM; repaglinide, 3.9 μM). SIGNIFICANCE STATEMENT: Some types of loop diuretics, statins, angiotensin receptor blockers, and glinides were predicted to affect URAT1, based on their chemical structural similarity to salicylic acid, the structure of which allows it to interact with URAT1. Glinides in particular showed cis- and trans-inhibitory activity toward URAT1."

Journal

Preparation, in vitro and in vivo evaluation of a novel mitiglinide microemulsions. (PubMed, Saudi Pharm J) - "Generally, the MTGME (o/w) showed good effect on controlling hyperglycemia. Therefore, microemulsion can be used as an effective oral drug delivery system to improve the bioavailability of MTG."

Journal • Preclinical • Diabetes

Epigenomic Profiling Advises Therapeutic Potential of Leukotriene Receptor Inhibitors for a Subset of Triple-Negative Breast Tumors. (PubMed, Int J Mol Sci) - "Other studies compare the effects of Montelukast and Zafirlukast (inhibitors of the cysteinyl leukotriene receptor, which is different from LTB4R/LTB4R2) on the MDA-MB-231 (TNBC) cell line, with high methylation and low expression levels of LTB4R...LY255283, Minocycline, Silibinin, Piceatannol, Mitiglinide, 1-Azakenpaullone, Carbetocin, and Pim-1-inhibitor-2 can be considered as candidates for the additional treatment of TNBC patients with tumors demonstrating LTB4R/LTB4R2 hypomethylation/upregulation. Finally, our results suggest that the epigenetic status of leukotriene B4 receptors is a novel, potential, predictive, and prognostic biomarker for TNBC. These findings might improve individualized therapy for TNBC patients by introducing new therapeutic adjuncts as anticancer agents."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • LTB4R2

Reduced blood glucose levels by the combination of vadadustat in an elderly patient with chronic kidney disease who was receiving mitiglinide and sitagliptin: a case report. (PubMed, J Pharm Health Care Sci) - "Hypoglycemia was observed when sitagliptin, mitiglinide, and vadadustat were concomitantly administered, which may have resulted in a drug-drug interaction between vadadustat and sitagliptin via OAT3 inhibition in the renal tubules."

Journal • Chronic Kidney Disease • Diabetes • Hematological Disorders • Hypoglycemia • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • STAT3

Design, preparation, and in vitro evaluation of gastroretentive floating matrix tablet of mitiglinide. (PubMed, Front Pharmacol) - "Furthermore, radiographic examination indicated that the tablets remained afloat in gastric fluid for up to 12 h in the rabbit's stomach. In conclusion, the developed floating matrix tablet of mitiglinide could be regarded as a promising formulation that could release the drug in the stomach at a controlled rate and, hence, offer better management of type II diabetes."

Journal • Preclinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Structural Insights Into the High Selectivity of the Anti-Diabetic Drug Mitiglinide. (PubMed, Front Pharmacol) - "Mitiglinide locks SUR1 in the NBD-separated inward-facing conformation. The detailed structural analysis of the mitiglinide-binding site uncovers the molecular basis of its high selectivity."

Journal • Diabetes • Metabolic Disorders

A novel and simple dynamic coating capillary electrophoresis method for the chiral separation and quantification of mitiglinide enantiomers using hydroxyethyl cellulose as a dynamic coating agent. (PubMed, Pharmazie) - "The newly developed method was effectively applied to the assay of enantiomers of MTG in pharmaceutical formulations. Additionally, it was proven to have the advantages of being simple, rapid, and accurate."

Journal

Chromatographic Separation of the Novel Hypoglycemic Drug Mitiglinide in its Bulk Powder and Pharmaceutical Formulation: Forced Degradation and Validated Stability-Indicating HPTLC/Densitometry and HPLC/UV Methods. (PubMed, J AOAC Int) - "Statistical comparison between the results obtained from the developed methods and those obtained by the reported HPLC method showed no significance difference."

Journal • Diabetes • Metabolic Disorders

Comparison of the efficacy of repaglinide versus the combination of mitiglinide and voglibose on glycemic variability in Japanese patients with type 2 diabetes. (PubMed, Curr Pharm Des) - "Treatment with the combination of mitiglinide and voglibose might be more effective than repaglinide for the improvement of glycemic variability."

Clinical • Journal • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

A prospective, randomized, multicenter trial comparing the efficacy and safety of the concurrent use of long-acting insulin with mitiglinide or voglibose in patients with type 2 diabetes. (PubMed) - "The prevalence of adverse events and the risk of hypoglycemia were similar for both groups. Combination therapy with mitiglinide plus basal insulin glargine was non-inferior to voglibose plus basal insulin glargine in terms of the effect on overall glycemic control."

Journal • Biosimilar • Diabetes

Match-101: Efficacy and Safety of Mitiglinide vs Acarbose in Patients With Type 2 Diabetes Mellitus (clinicaltrials.gov) - P4; N=248; Completed; Sponsor: Zhongda Hospital; Active, not recruiting ➔ Completed; Trial primary completion date: Sep 2015 ➔ Dec 2015

Trial completion • Trial primary completion date • Biosimilar • Diabetes

Effect of Food Thickener on the Inhibitory Effect of Mitiglinide Tablets on Post-prandial Elevation of Blood Glucose Levels. (PubMed) - Dysphagia - "The extended time of higher glucose levels associated with thickener-immersed MGN tablets given to human volunteers may be associated with the reduced disintegration rates of immersed MGN tablets as observed in the in vitro experiment. Overall, our study suggests that commercially available food thickeners influence the pharmacodynamics of MGN and that their use should therefore be carefully assessed and monitored in certain clinical situations."

Journal • Biosimilar

Tighter glycemic control is associated with ADL physical dependency losses in older patients using sulfonylureas or mitiglinides: Results from the DIMORA study. (PubMed) - "Tighter glycemic control was associated with ADL physical dependency losses, especially in those using sulfonylureas and mitiglinides."

Journal • Biosimilar • Diabetes

The vasorelaxant effect of mitiglinide via activation of voltage-dependent K(+) channels and SERCA pump in aortic smooth muscle. (PubMed, Life Sci) - "We proposed that mitiglinide induces vasorelaxation via activation of Kv channels and SERCA pump. However, the vasorelaxant effects of mitiglinide did not involve other K(+) channels, Ca(2+) channels, PKA/PKG signaling pathways, or the endothelium."

Journal • Biosimilar • Diabetes • Metabolic Disorders

Sitagliptin versus mitiglinide switched from mealtime dosing of a rapid-acting insulin analog in patients with type 2 diabetes: a randomized, parallel-group study. (PubMed) - "Sitagliptin may predominantly act on FPG, whereas mitiglinide may act on postprandial plasma glucose to achieve glycemic control after switching from a bolus insulin regimen. Additional therapy to sitagliptin or mitiglinide is clearly required to obtain equivalent glycemic control in patients using a higher dose of insulin."

Journal • Biosimilar • Diabetes

"Gastroretentive Co-Solvent based In situ Gel as a promising approach for Simultaneous Extended Delivery and Enhanced Bioavailability of Mitiglinide Calcium". (PubMed, J Pharm Sci) - "These systems are unsuitable for poorly water-soluble drugs such as the novel antidiabetic drug mitiglinide calcium (MTG). Thus our goal is to assess the possibility of using co-solvency approach in formulating gastroretentive in situ gel of the short half-life MTG to simultaneously enhance its bioavailability and sustain its release."

Journal

Pharmacokinetic and Pharmacodynamic Study of Glufast Tablets 10mg(Mitiglinide) (clinicaltrials.gov) - P4; N=16; Completed; Sponsor: Orient Europharma Co., Ltd.

Clinical • New P4 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Risk of hypoglycemia associated with repaglinide combined with clopidogrel, a retrospective cohort study. (PubMed, J Pharm Health Care Sci) - "These findings indicate that minimum plasma glucose levels were significantly decreased in patients taking repaglinide and clopidogrel. Considering the risk of hypoglycemia associated with taking repaglinide and clopidogrel, when a glinide is required in patients taking clopidogrel, mitiglinide may be a better choice."

Journal • Retrospective data • CYP2C8

Risk of Hypoglycemia After Concomitant Use of Antidiabetic, Antihypertensive, and Antihyperlipidemic Medications: A Database Study. (PubMed, J Clin Pharmacol) - "Concomitant use of linagliptin/glibenclamide, sitagliptin/glibenclamide, sitagliptin/buformin, exenatide/voglibose, mitiglinide/perindopril, repaglinide/barnidipine, alogliptin/cilnidipine, teneligliptin/barnidipine, teneligliptin/urapidil, exenatide/candesartan, voglibose/barnidipine, voglibose/guanabenz, or exenatide/tocopherol was noted using the 2 criteria for drug-drug interactions. The concomitant use of sitagliptin/buformin, exenatide/voglibose, repaglinide/barnidipine, teneligliptin/barnidipine, teneligliptin/urapidil, exenatide/candesartan, voglibose/barnidipine, voglibose/guanabenz, or exenatide/tocopherol was detected in both the JADER and Food and Drug Administration Adverse Event Reporting System databases. Combination therapy with the drugs listed above would show potential interactions that could result in hypoglycemia in patients with diabetes mellitus."

Journal

Rhabdomyolysis risk from the use of two-drug combination of antidyslipidemic drugs with antihypertensive and antidiabetic medications: a signal detection analysis. (PubMed, Fundam Clin Pharmacol) - "We assessed the risk of rhabdomyolysis for the two-drug concomitant use of antidyslipidemic drugs (statin, fibrate, and ezetimibe) with antihypertensive and antidiabetic medications. Concomitant use of pravastatin/fenofibrate, simvastatin/mefruside, fluvastatin/temocapril, bezafibrate/temocapril, bezafibrate/spironolactone, bezafibrate/metoprolol, bezafibrate/losartan, fluvastatin/mitiglinide, or fenofibrate/glibenclamide was detected as the signal of rhabdomyolysis in this analysis. Combination therapy with the drugs listed above has the potential of drug-drug interactions that could result in rhabdomyolysis in patients with dyslipidemia."

Journal

Reversed-phase liquid chromatography separation and mass spectrometry fragmentation analysis of mitiglinide and three isomers (PubMed, Se Pu) - "Isomer impurity 1 was degraded at high temperature, while isomer impurities 2 and 3 were determined to be synthetic impurities. In addition, samples of mitiglinide calcium raw materials were analyzed."

Journal

Ease of Taking and Palatability of Fixed-Dose Orally Disintegrating Mitiglinide/Voglibose Tablets. (PubMed, Chem Pharm Bull (Tokyo)) - "Taste evaluation results did not reveal any difference between FDC-ODT and IC-ODTs, except for the sweetness score after spitting out. In conclusion, FDC-ODT is easy to take and can help improve patient adherence."

Journal

Enhancement of postprandial endogenous insulin secretion rather than exogenous insulin injection ameliorated insulin antibody-induced unstable diabetes: a case report. (PubMed, BMC Endocr Disord) - "Proper enhancement of postprandial endogenous insulin aimed at suppressing postprandial glucose output without stimulating excessive glucose uptake in the periphery is potentially useful for treating diabetes with insulin antibody-induced glycemic instability."

Clinical • Journal