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Linagliptin has protective effects on the retinal neurovascular unit but, in proliferative retinopathy, dipeptidyl peptidase 4 (DPP-4) inhibition could be detrimental. The aim of this study was to assess the effect of linagliptin on ischaemia-induced neovascularisation of the retina.
The two dipeptidyl peptidase (DPP)-4 inhibitors, linagliptin and sitagliptin, were shown to exert different binding kinetics in vitro. Twenty-four hours after oral dosing particularly in vivo inhibition of renal-specific DPP-4 activity was more sustained in Sprague Dawley rats after exposure to linagliptin than it was after sitagliptin.
A validated LC-MS/MS method for simultaneous determination of linagliptin and metformin in spiked human plasma coupled with solid phase extraction: Application to a pharmacokinetic study in healthy volunteers.
Combination therapy has a pivotal role in type II diabetes mellitus management in patients unable to maintain normal glycemic level using metformin alone. Addition of linagliptin, dipeptidyl peptidase-IV inhibitor, to metformin improves glycemic control. This study is concerned with the development of an HPLC-MS/MS method for simultaneous quantification of linagliptin and metformin in spiked human plasma. The method was applied to evaluate the potential pharmacokinetic interactions between the cited drugs i...
Two 52-week Phase III studies evaluated the efficacy and safety of once-daily combinations of empagliflozin/linagliptin as monotherapy or add-on to metformin in patients with type 2 diabetes (T2DM). The aim of this analysis was to further assess the safety and tolerability of empagliflozin/linagliptin compared with their individual components in patients with T2DM, using pooled data from these trials.
To determine whether linagliptin, a dipeptidyl peptidase 4 inhibitor, can promote the recovery of cardiac function after hypothermic preservation.
Multiple sclerosis is a chronic inflammatory demyelinating central nervous system disorder leading to serious neurological deficits. Linagliptin, a dipeptidyl peptidase-4 inhibitor, recently showed neuroprotective properties against neurodegenerative diseases. This study investigated the possible neuroprotective effect of linagliptin against cuprizone-induced demyelination in mice and its potential early-remyelinating properties. C57Bl/6 mice were fed chow containing 0.7% cuprizone for 1 week, followed by...
Hypertrophic scar (HS) is a fibro-proliferative disease after serious burns, the underlying mechanism remains unknown. The study was performed to clarify the effect of high glucose (HG) on HS. The expression of Col1, Col3 and α-SMA were up-regulated in HS derived fibroblasts (HSFs) exposed to HG (20mM, 30mM), and HG activated the phosphorylated protein expression of IGF/Akt/mTOR signaling pathway in HSFs. Dpp4, a marker targeted the treatment of diabetes mellitus, was overexpressed in HG-induced HSFs. Lina...
Numerous patients develop diabetes in response to glucocorticoid therapy. This study explored the efficacy, safety, and preventive potential of the dipeptidyl peptidase-4 inhibitor, linagliptin (TRADJENTA®), in the development of glucocorticoid-induced diabetes mellitus.
Dipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects on diabetic kidney disease (DKD) via specific antioxidant pathways. The DPP-4 inhibitor, linagliptin, was evaluated with the hypothesis that DPP-4 inhibition would ameliorate the development of DKD in a glucose-independent manner by altering specific antioxidant function.
Complex regional pain syndrome (CRPS) is a debilitating neurologic disorder with an interlinked and yet incompletely defined pathogenesis. Treatment options remain a therapeutic challenge. Linagliptin is one of the dipeptidyl peptidase-4 (DPP-4) inhibitors which are used for the treatment of diabetes mellitus. Apart from the improvement of glycemic control, accumulating evidence points to the beneficial effects of DPP-4 inhibitors in a wide array of conditions. Herein, the present study was outlined to inve...
To investigate the risk of hypoglycaemia in people aged ≥65 years with type 2 diabetes mellitus (T2DM) treated with linagliptin, in the largest pooled analysis performed to date.
Combination of APD668, a G protein-coupled receptor 119 agonist with linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in a murine model of non-alcoholic steatohepatitis with diabetes.
Non-alcoholic steatohepatitis (NASH) is characterized by the presence of hepatic steatosis, oxidative stress, inflammation, and hepatocyte injury with or without fibrosis. In this study, we explored the effect of APD668, a GPR119 agonist alone or in combination with linagliptin, a DPPIV inhibitor, on the progression of steatohepatitis in a murine model of NASH with diabetes. A novel NASH model with diabetes was generated by administration of streptozotocin injection to neonatal C57BL/6 mice (2-3 days old)...
Which is better, high-dose metformin monotherapy or low-dose metformin/ linagliptin combination therapy, in improving glycemic variability in type 2 diabetes patients with insufficient glycemic control despite low-dose metformin monotherapy: A randomized, crossover, CGM-based, pilot study.
This study investigates the effect of high-dose metformin or low-dose metformin/linagliptin combination therapy on glycemic variability (GV) in type 2 diabetes (T2D) patients with insufficient glycemic control despite low-dose metformin monotherapy in a crossover study using continuous glucose monitoring (CGM).
Structural re-positioning, in silico molecular modelling, oxidative degradation, and biological screening of linagliptin as adenosine 3 receptor (ADORA3) modulators targeting hepatocellular carcinoma.
Chemical entities with structural diversity were introduced as candidates targeting adenosine receptor with different clinical activities, containing 3,7-dihydro-1H-purine-2,6-dione, especially adenosine 3 receptors (ADORA3). Our initial approach started with pharmacophore screening of ADORA3 modulators; to choose linagliptin (LIN), approved anti-diabetic drug as Dipeptidyl peptidase-4 inhibitors, to be studied for its modulating effect towards ADORA3. This was followed by generation, purification, analytic...
The limited linear range of UV-Visible spectrophotometry may be insufficient to occupy multiple components with wide variations in their concentrations or absorptivities that will hinder the simultaneous spectrophotometric determination and may require spiking or measurements in subsequent dilution steps. The current work introduces the absorptivity target concentration (ATC) values, a simple way for the proper choice of the working spectral region to execute accurate and linear spectrophotometric measureme...
Dipeptidyl peptidase-4 (DPP4) inhibitors are known to have a protective effect on diabetic kidney disease, possibly via reduction of oxidative stress and inflammation in the kidney. However, whether these potential mechanisms play a role in non-diabetic proteinuric kidney diseases is not clear.
Diabetes mellitus is a progressive disease with cardiovascular complications. This study evaluated the effects of liraglutide, a glucagon-like peptide-1 analog, and the dipeptidyl peptidase 4 inhibitors sitagliptin and linagliptin on cardiac function in type 2 diabetes patients with renal impairment.
The aim is to evaluate the efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4-I: sitagliptin, saxagliptin, linagliptin, vildagliptin and alogliptin) in patients with type 2 diabetes.
Dipeptidyl-peptidase-4 (DPP-4) inhibitors, as the most recent available anti-diabetic agents, were generally used in clinical treatment of type 2 diabetes (T2DM). In addition to anti-diabetic effects, the five most widely used DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin) also exert cardiovascular protective effects. In recent years, increasing studies suggest that sitagliptin shows pleiotropic impacts towards the cardiovascular system either with or without diabetes....
Using an operational continuum of healthy aging developed by U.S. researchers, we sought to estimate the prevalence of healthy aging among older Spaniards, inform the development of a definition of healthy aging in Spain, and foster cross-national research on healthy aging.
The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin (VG) is used to treat type 2 diabetes. In rare cases, VG-induced liver injury has been reported. One case report suggested that immune responses were involved in the hepatotoxicity. However, the underlying mechanisms of VG-induced hepatotoxicity are uncertain. In the present study, we investigated whether VG has the potential to covalently bind to macromolecules in cells, a process that could initiate immune-mediated hepatotoxicity. For comparison, M...
According to ICH guideline Q6A, dissolution testing can be replaced by disintegration testing if it can be shown that the active pharmaceutical ingredient (API) is highly soluble and the formulation is rapidly releasing. In addition, a relationship between dissolution and disintegration has to be established. For a fixed-dose combination tablet of empagliflozin and linagliptin this relationship was established by applying two different approaches. In the first approach, the extent to which the disintegratio...
We have previously shown that albuminuria and renal levels of advanced glycation end products (AGEs), receptor for AGEs (RAGE), and oxidative stress are suppressed in dipeptidyl peptidase-4 (DPP-4)-deficient diabetic rats, thus suggesting the crosstalk between AGE-RAGE axis and DPP-4 in experimental diabetic nephropathy. Therefore, we examined here the role of DPP-4 in AGE-evoked inflammatory reactions in human proximal tubular cells. Proteins were extracted from proximal tubular cells, and conditioned medi...
The American Nurses Association declared 2017 the Year of the Healthy Nurse. In an effort to promote a healthy academic environment, faculty and staff in institutions of higher learning should serve as role models for healthy living for their students. This article describes an innovative approach to cultivating a healthy academic environment. Details about planning and implementation are provided along with recommendations for future implementation.