Omarigliptin

Galloway, Iona; McKay, Gerry; Fisher, Miles

doi:10.1002/pdi.2086

Cited by 6 publications

(8 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the peptidomimetic DPP-4 inhibitors were related to enzymatic cleavage, the non-peptidomimetic inhibitors are now being explored. Linagliptin, anagliptin, omarigliptin, and trelagliptin are non-peptidomimetic DPP-4 inhibitors that have been launched, while carmegliptin and imigliptin are under clinical trials [13][14][15][16][17].The α-glucosidase inhibitors show minimal effects in inducing hypoglycemia and in weight loss. The main downside of α-glucosidase inhibitors is abdominal discomfort due to its mechanism in preventing the degradation of polysaccharides into monosaccharides.…”

mentioning

confidence: 99%

An Integrated In Silico and In Vitro Assays of Dipeptidyl Peptidase-4 and α-Glucosidase Inhibition by Stellasterol from Ganoderma australe

et al. 2019

View full text Add to dashboard Cite

Background: Ganoderma fungus is rich in terpenoids. These compounds are known for their anti-hyperglycemic activities. However, the study of terpenoids as the secondary metabolite from Ganoderma as a dipeptidyl peptidase-4 (DPP-4) inhibitor remains unexplored. In addition, we examined the α-glucosidase inhibition activity. Objective: This study aimed to isolate the major terpenoid from non-laccate Ganoderma and examined its inhibitor activity on DPP-4 and α-glucosidase enzymes, and its interaction. Methods: The compound was isolated using column chromatography from Ganoderma australe. The structure of the isolated compound was confirmed by 1H and 13C nuclear magnetic resonance spectroscopy, while the inhibitory activity was evaluated using an enzymatic assay. The interaction of the isolated compound with DPP-4 and α-glucosidase enzymes was investigated using an in silico study. Results: The isolated compound was identified as stellasterol; IC50 values for DPP-4 and α-glucosidase inhibitor were 427.39 µM and 314.54 µM, respectively. This study revealed that the inhibitory effect of stellasterol on DPP-4 enzyme is through hydrophobic interaction, while the α-glucosidase enzyme is due to the interaction with six amino acids of the enzyme. Conclusion: Stellasterol is the major component of the steroid from G. australe. Enzyme inhibitory assay and in silico study suggest that stellasterol may contribute antidiabetic activity with a mechanism closer to acarbose rather than to sitagliptin.

show abstract

mentioning

confidence: 99%

An Integrated In Silico and In Vitro Assays of Dipeptidyl Peptidase-4 and α-Glucosidase Inhibition by Stellasterol from Ganoderma australe

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Out of the once-weekly DPP4is, trelagliptin does not have a CV trial linked to it. Omarigliptin was undergoing CV assessment in a trial expected in 2021; however, the trial was terminated by the company MSD earlier than schedule (in 2016), with the announcement that the decision was made for marketing purposes and not for medical reasons [ 51 , 52 ].…”

Section: Available Hypoglycemic Classesmentioning

confidence: 99%

The Landscape of Glucose-Lowering Therapy and Cardiovascular Outcomes: From Barren Land to Metropolis

Nasrallah

Khalil

Refaat

2017

BioMed Research International

View full text Add to dashboard Cite

The choice of glucose-lowering therapy (GLT) has expanded to include 11 different classes in addition to insulin. Since the 2008 Food and Drug Administration guidance for industry and mandate of demonstrating cardiovascular (CV) safety prior to any new drug approval, there were several trials primarily conducted to establish that goal. Some had neutral effects, while there were positively beneficial outcomes with more recent studies. Hospitalization for congestive heart failure has also been a heterogeneous finding among the different classes of GLT, with drug outcomes ranging from risky to beneficial. The current review selectively focuses on the evidence for CV outcomes for each class of GLT and summarizes the existing guidelines with regard to these drugs in heart disease. Moreover, it illustrates the dynamic status in the development of evidence. Finally, the review enables healthcare providers to formulate a plan for hypoglycemic therapy which will optimize CV health, in a patient-centered manner.

show abstract

“…Gliptins are considered to be effective agents for the treatment of type 2 Diabetes Mellitus. Omariglitpin (OTN), Figure 1 , is a long-acting once weekly administered antidiabetic drug acting as dipeptidyl peptidase-4 (DPP-4) inhibitor [ 5 , 6 , 7 ]. It has been licensed for use in Japan since 2015 but its phase III development in US has been halted for undisclosed commercial reasons [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Omariglitpin (OTN), Figure 1 , is a long-acting once weekly administered antidiabetic drug acting as dipeptidyl peptidase-4 (DPP-4) inhibitor [ 5 , 6 , 7 ]. It has been licensed for use in Japan since 2015 but its phase III development in US has been halted for undisclosed commercial reasons [ 5 ]. It improved the glycated hemoglobin A1c (HbA1c) as it reversibly inhibits DPP-4 enzyme, which prolongs the circulating half-life of glucagon-like peptide-1 (GLP-1) increasing insulin secretion.…”

Section: Introductionmentioning

confidence: 99%

“…It improved the glycated hemoglobin A1c (HbA1c) as it reversibly inhibits DPP-4 enzyme, which prolongs the circulating half-life of glucagon-like peptide-1 (GLP-1) increasing insulin secretion. Contrary to the once-daily administered DPP-4 inhibitors available in market, once-weekly administered OTN can improve patients’ compliance to the treatment protocol [ 5 , 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers

et al. 2020

View full text Add to dashboard Cite

Enhancing drug extraction from human plasma is a challenging approach that critically affects pharmacokinetic and any further clinical studies based on the drug Cmin and Cmax values. It also has a serious impact on the sensitivity and the lower limit of quantification (LLOQ) value of the bio-analytical methods. An advanced liquid chromatography tandem mass spectrometry (LC-MS/MS) bio-analytical method of omarigliptin (25–1000 nM) was established in human plasma using one-step liquid-liquid extraction. Alogliptin was used as an internal standard (IS) to attain good recovery and reproducibility while reducing the effects of the matrix. Enhanced plasma extraction of omarigliptin was successfully achieved with tertiary butyl methyl ether—diethyl ether (TBME-DEE) mixture as the extracting solvent, while using acetonitrile as the diluent solvent for the IS to effectively decrease the formed emulsion. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 399.2 to 153.0 for omarigliptin and m/z 340.2 to 116.0 for alogliptin was employed in positive Electro Spray Ionization (ESI) mode. Human plasma samples were collected after 1.5 h (tmax) of Marizev® (12.5 mg) tablets administration to healthy human volunteers showing average concentration of 292.18 nM. Validation results were all satisfactory including successful stability studies with bias below 12%. The proposed study will be valuable for ethnicity comparison studies that will be commenced on omarigliptin in Egypt by the authors in prospective study, following the FDA recommends, to evaluate possible sub-group dissimilarities that include pharmacokinetic parameters.

show abstract

Omarigliptin

Cited by 6 publications

References 4 publications

An Integrated In Silico and In Vitro Assays of Dipeptidyl Peptidase-4 and α-Glucosidase Inhibition by Stellasterol from Ganoderma australe

An Integrated In Silico and In Vitro Assays of Dipeptidyl Peptidase-4 and α-Glucosidase Inhibition by Stellasterol from Ganoderma australe

The Landscape of Glucose-Lowering Therapy and Cardiovascular Outcomes: From Barren Land to Metropolis

Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers

Contact Info

Product

Resources

About