Value-based sitagliptin

PURPOSE: Adefovir (as dipivoxil) was selected as a probe drug in a previous transporter cocktail phenotyping study to assess renal organic anion transporter 1 (OAT1), with renal clearance (CLR ) as the primary parameter describing renal elimination. An approximately 20% higher systemic exposure of adefovir was observed when combined with other cocktail components (metformin, sitagliptin, pitavastatin, and digoxin) compared to sole administration. The present evaluation applied a population pharmacokinetic (popPK) modeling approach to describe adefovir pharmacokinetics as a cocktail component in more detail...

The application of (R)-ω-transaminases as biocatalysts for chiral amine synthesis has been hampered by inadequate stereoselectivity and narrow substrate spectrum. Herein, an effective evolution strategy for (R)-ω-transaminase designing for the asymmetric synthesis of sitagliptin intermediate is presented. Since natural transaminases lack activity toward bulky prositagliptin ketone, transaminase scaffolds with catalytic machinery and activity toward the truncated prositagliptin ketone were firstly screened based on substrate walking principle...

This article sheds light on the various scaffolds that can be used in the designing and development of novel synthetic compounds to create DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a variety of scaffolds with high DPP-4 inhibition activity, such as pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, β-carbonyl 1,2,4-triazole, and quinazoline motifs. The article further explains that the potential of the compounds can be increased by substituting atoms such as fluorine, chlorine, and bromine...

Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation...

Introduction Diabetes mellitus is a syndrome affecting more than 28.7 million people worldwide and its prevalence in Pakistan is reported to be about 11%. Management includes lifestyle changes and varied therapeutic regimens. Metformin (MET) alone and in combinations is considered as an important agent for glycemic control. Our study is based on MET combination therapy with empagliflozin versus sitagliptin in order to achieve glycemic control. Methods This randomized clinical trial was conducted in the Department of Medicine and Allied of Federal Government Polyclinic Hospital, Islamabad, from January 2022 till June 2022...

A series of novel pyridazine-acetohydrazide hybrids were designed, synthesized, and evaluated for their in vitro and in vivo antihyperglycemic activity. In this context, pyridazine-acetohydrazides (6a-6p) were synthesized by coupling substituted aldehyde with 2-(5-cyano-6-oxo-3,4-diphenylpyridazine-1-6H-yl) acetohydrazide, which was prepared via the reaction of pyridazine ester with hydrazine hydrate. The molecular docking study was carried out to examine the binding affinities and interaction of designed compounds against the DPP-4 enzyme...

Chiral drugs are of great significance in drug development and life science because one pair of enantiomers has a different combination mode with target biological active sites, leading to a vast difference in physical activity. Metal-organic framework (MOF)-based chiral hybrid materials with specific chiral sites have excellent applications in the highly effective sensing of drug enantiomers. Sitagliptin and clonidine are effective curing drugs for controlling diabetes and hypertension, while insulin and norepinephrine are the biomarkers of these two diseases...

OBJECTIVE: The aim of this study was to compare the clinical outcomes associated with different combinations of oral diabetic drugs among patients with type 2 diabetes mellitus. METHOD: A prospective multicenter longitudinal, noninterventional observation study design was applied. At baseline (0 month), clinical parameters including glucose profile, renal function, lipid profile and risk assessment for cardiovascular risks were calculated. Mean Weighted difference (MWD) with heterogeneity and effect z was calculated to determine the risk reduction at the end of the study...

OBJECTIVES: In Chile, > 900,000 people with type 2 diabetes mellitus (DM2) are controlled in the Cardiovascular Health Program (PSCV). Even though the PSCV includes a set of interventions for the control of patients with DM2, the results are still insufficient, generating a high human, economic, and social cost. This study aimed to identify and select new health technologies for the control of patients with DM2 not currently incorporated into the PSCV to be proposed as candidates for an economic evaluation in the Chilean context...

Aims: We evaluated the efficacy and significant changes in the levels of retinol-binding protein 4 (RBP-4) and insulin resistance in patients with type 2 diabetes mellitus (T2DM) treated with chiglitazar versus sitagliptin. Methods: Eighty-one T2DM patients with haemoglobin A1c (HbA1c) level of 7.5%-10.0% were selected. Based on the study criteria, patients were randomly assigned to receive chiglitazar (32 mg), chiglitazar (48 mg), or sitagliptin (100 mg) orally for 24 weeks...

AIMS: To evaluate glycemic variations, changes in insulin resistance and oxidative stress after chiglitazar or sitagliptin treatment in untreated patients with type 2 diabetes mellitus (T2DM). METHODS: Based on the study inclusion and exclusion criteria, 81 patients with T2DM were randomly divided to receive chiglitazar or sitagliptin treatment for 24 weeks. Continuous glucose monitoring (CGM) systems were conducted for 72 h in eligible patients. We analyzed the following glycemic variation parameters derived from the CGM data and measured the serum levels of hemoglobin A1c (HbA1c), fasting blood glucose (FBG), 2-h postprandial blood glucose (2-h PBG), fasting insulin (Fins) and inflammatory-related indicators at baseline and the end of the study...

The pharmacokinetic profiling of active compounds is necessary for drug development and application. Approaches to a pharmacokinetic study based on biological markers are alternatives to traditional approaches based on chromatographic methods. The aim of the study was to compare two analytical approaches to pharmacokinetics investigation for an example of sitagliptin in rabbits after one dose oral administration. The method for sitagliptin quantification in rabbit plasma samples based on a correlation between its concentration and dipeptidyl peptidase IV activity was proposed, validated, and applied...

BACKGROUND: Medicine purchasing in Chinese public hospitals is decided by the hospital Pharmacy Management Committee (PMC), that is complex, subjective and requires efficient approaches to ensure transparency and consistency for the factors being considered. This study aimed to use the Evidence and Value: Impact on Decision Making (EVIDEM) framework to assess medicine in these hospitals. In this study anti-diabetic drugs DPP-4 inhibitors, which work by inhibiting the activation of the Dipeptidyl Peptidase 4 (DPP-4) inhibitors, were appraised...

Dipeptidyl peptidase-IV (DPP-IV) plays a critical role in glucose metabolism and has become an important target for type 2 diabetes mellitus. We previously reported a two-photon fluorescent probe glycyl-prolyl-N-butyl-4-amino-1,8-naphthalimide (GP-BAN) for DPP-IV detection with high specificity and sensitivity. In this study, a high-throughput screening (HTS) method for DPP-IV inhibitors using human plasma as the enzyme source was established and optimized. Further investigations demonstrate that the IC50 value of sitagliptin (listed as the DPP-IV inhibitor) determined with human recombinant DPP-IV (36...

BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide 1 (GLP-1) receptor agonist to be approved in the United States for glycemic control in people with type 2 diabetes mellitus (T2DM). While oral semaglutide is not indicated for reduction of cardiovascular event risk, its label does include evidence of no increase in cardiovascular risk in people who received oral semaglutide. OBJECTIVE: To estimate the incremental value of oral semaglutide added to existing antihyperglycemic treatment for people with T2DM with additional risk for cardiovascular disease...

Dipeptidyl peptidase-4 (DPP-4) inhibition has been recognized as a promising approach to develop safe and potent antidiabetic agents for the management of type 2 diabetes. In this context, new thiosemicarbazones ( 2a - o ) were prepared efficiently by the reaction of aromatic aldehydes with 4-[4-(1 H -pyrazol-1-yl)phenyl]thiosemicarbazide ( 1 ), which was obtained via the reaction of 4-(1 H -pyrazol-1-yl)phenyl isothiocyanate with hydrazine hydrate. Compounds 2a - o were evaluated for their DPP-4 inhibitory effects based on a convenient fluorescence-based assay...

To demonstrate the potential of Raman spectroscopy for the qualitative and quantitative analysis of solid dosage pharmacological formulations, different concentrations of Sitagliptin, an Active Pharmaceutical Ingredient (API) currently prescribed as an anti-diabetic drug, are characterised. Increase of the API concentrations induces changes in the Raman spectral features specifically associated with the drug and excipients. Principal Component Analysis (PCA) and Partial Least Squares Regression (PLSR), were used for the qualitative and quantitative analysis of the spectral responses...

Recently, an increasing number of pharmaceutical compounds has become fluorinated. Owing to their pharmacological efficacy, the use of these fluorinated pharmaceuticals continues to grow, and they constitute 20% of the drugs on the current market. However, only a few studies have investigated the fate and transformation of these emerging contaminants in natural and engineered aquatic environments. In the present study, the H2 -based reductive transformation of three fluorinated pharmaceutical compounds (levofloxacin, sitagliptin, and fluoxetine) were investigated using alumina-supported monometallic and bimetallic catalysts of the Pt-group noble metals (i...

Mucoadhesive nanoparticles represent a potential drug delivery strategy to enhance the therapeutic efficacy in oral therapy. This study assessed the prospective of developing HPMC- and PLGA-based nanoparticles using a nanospray drier as a mucoadhesive extended release drug delivery system for sitagliptin and evaluated their potential in an animal model. Nanoparticles were prepared using a Buchi® B-90 nanospray drier. Optimization of particle size was performed using response surface methodology by examining the influence of spray-drying process variables (inlet temperature, feed flow, and polymer concentration) on the particle size...

Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase-4, used for the treatment of type 2 diabetes mellitus. The crystal structure of active pharmaceutical solids determines their physical and chemical properties. The polymorphism, solvates and hydrates can influence the free energy, thermodynamic parameters, solubility, solid-state stability, processability and dissolution rate, besides directly affecting the bioavailability. Thus, the physicochemical characterization of an active pharmaceutical ingredient is required to guarantee the rational development of new dosage forms...