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PloS One 2022Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that is used orally in conjunction with diet and exercise to control sugar levels in type 2 Diabetes Mellitus...
Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that is used orally in conjunction with diet and exercise to control sugar levels in type 2 Diabetes Mellitus patients. This study aimed to extemporaneously prepare SiP solution (1% w/v) using pure Sitagliptin phosphate (SiP) powder and assess its stability according to pharmaceutical regulatory guidelines. Four SiP solutions, coded T1, T2, T3, and T4, were extemporaneously prepared using pure SiP powder as a source of API. The most suitable one, in terms of general organoleptic properties, was selected for further investigations, including stability studies. For this last purpose, samples of the T4 solution were kept under two storage conditions, room temperature (25˚C and 60% Relative Humidity) and accelerated stability conditions (40˚C and 75% Relative Humidity). Assay, pH, organoleptic properties, related substances, and microbial contamination were evaluated for 4 consecutive weeks. A High-Performance Liquid Chromatography (HPLC) analytical method was developed and validated to be used for the analysis and quantification of SiP in selected solution formulation. The adopted formula had a pH on the average of 3 to 4. During the stability tests, all pH values remained constant. Furthermore, after 4 weeks of storage under both conditions, the SiP concentration was close to 100%. A stable SiP extemporaneous solution was successfully prepared using pure SiP powder. Patients with swallowing problems who use feeding tubes and are unable to take oral solid dosage forms may benefit from this research. Community pharmacists can prepare the solution using sitagliptin powder as the source of the active ingredient.
Topics: Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2; Drug Compounding; Drug Stability; Drug Storage; Humans; Powders; Sitagliptin Phosphate
PubMed: 35294449
DOI: 10.1371/journal.pone.0262068 -
Andrologia Apr 2021Sitagliptin increases the levels of incretin hormones and stimulates a decrease in blood glucose levels, by blocking the DPP4 enzyme. We have very limited information...
Sitagliptin increases the levels of incretin hormones and stimulates a decrease in blood glucose levels, by blocking the DPP4 enzyme. We have very limited information about impact of sitagliptin on male genital system and relationship between sitagliptin/diabetes/ER. Fucoidan can be effective in blood glucose homeostasis. We goal to explain of the effect of sitagliptin and introduce an approach of fucoidan treatment in experimental diabetes in male rats. Fifty-eight Wistar albino rats were divided into C-control group and D-diabetes group: 60 mg/kg streptozotocin intraperitoneal (i.p.); DS group: STZ + 10 mg/kg sitagliptin intragastric (i.g.); DF group: STZ + 100 mg/kg fucoidan i.p.; and DSF group: STZ + 10 mg/kg sitagliptin + 100 mg/kg fucoidan. A significant decrease was detected when DS, DF and DSF groups compared to group D in blood glucose levels, basement membrane thickness and also apoptotic cell/tubule index, pJNK, caspase 3, caspase 12, GRP78, CHOP and DPP4. Sitagliptin and fucoidan have been found to be effective in blood glucose homeostasis and reducing the expression of certain proteins that lead to apoptosis and especially the proteins in the ER stress pathway. Therefore, we think that both sitagliptin and fucoidan can be effective in preventing or eliminating histopathological damages in diabetic testicular tissues, and their treatment effects can be used more.
Topics: Animals; Apoptosis; Diabetes Mellitus; Male; Polysaccharides; Rats; Rats, Wistar; Sitagliptin Phosphate; Testis
PubMed: 33474733
DOI: 10.1111/and.13858 -
Annals of Medicine 2023The emergence of genetically-modified human proteins and glucagon-like peptide-1 (GLP-1) receptor agonists have presented a promising strategy for effectively managing... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety profile of once-weekly Semaglutide versus once-daily Sitagliptin as an add-on to metformin in patients with type 2 diabetes: a systematic review and meta-analysis.
BACKGROUND
The emergence of genetically-modified human proteins and glucagon-like peptide-1 (GLP-1) receptor agonists have presented a promising strategy for effectively managing diabetes. Due to the scarcity of clinical trials focusing on the safety and efficacy of semaglutide as an adjunctive treatment for patients with type 2 diabetes who had inadequate glycemic control with metformin, we conducted a systematic review and meta-analysis. This was necessary to fill the gap and provide a comprehensive assessment of semaglutide compared to sitagliptin, a commonly prescribed DPP-4 inhibitor, in this patient population.
METHODS
A comprehensive and systematic search was carried out on reputable databases including PubMed, the Cochrane Library, and Elsevier's ScienceDirect to identify relevant studies that compared the efficacy of once-weekly Semaglutide with once-daily Sitagliptin in individuals diagnosed with type 2 diabetes mellitus. The analysis of the gathered data was performed utilizing the random-effects model, which considers both within-study and between-study variations.
RESULTS
The meta-analysis incorporated three randomized controlled trials (RCTs), encompassing 2401 participants, with a balanced distribution across the treatment groups. The primary focus of the study revolved around evaluating changes in HbA1C, blood pressure, pulse rate, body weight, waist circumference, and BMI. The findings revealed that once-weekly Semaglutide showed substantially improved HbA1C (WMD: -0.98; 95% CI: -1.28, -0.69, p-value: < 0.0001; I2: 100%), systolic (WMD: -3.73; 95% CI: -5.42, -2.04, p-value: <0.0001; I2: 100%) and diastolic blood pressures (WMD: -0.66; 95% CI: -1.02, -0.29, p-value: 0.0005; I2: 100%), and body weight (WMD: -3.17; 95% CI: -3.84, -2.49, p-value: <0.00001; I2: 100%) compared to once-daily Sitagliptin. However, there was an observed increase in pulse rate (WMD: 3.33; 95% CI: 1.61, 5.06, p-value: <0.00001; I2: 100%) associated with Semaglutide treatment. Regarding secondary outcomes, there was an elevated risk of total adverse events and premature treatment discontinuation with Semaglutide. The risk of serious, severe, moderate, and mild adverse events did not significantly differ between the two treatments.
CONCLUSIONS
In conclusion, the administration of once-weekly Semaglutide exhibited a substantial reduction in HbA1c, average systolic blood pressure (SBP), mean diastolic blood pressure (DBP), body weight, waist circumference, body mass index (BMI), and a rise in pulse rate, as opposed to the once-daily administration of Sitagliptin.
Topics: Humans; Metformin; Sitagliptin Phosphate; Glycated Hemoglobin; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Body Weight
PubMed: 37498865
DOI: 10.1080/07853890.2023.2239830 -
Bioanalysis Aug 2023A chiral HPLC technique was developed to determine sitagliptin phosphate enantiomers in rat plasma in compliance with US FDA regulations. The technique used a...
A chiral HPLC technique was developed to determine sitagliptin phosphate enantiomers in rat plasma in compliance with US FDA regulations. The technique used a Phenomenex column with a mobile phase consisting of a 60:35:5 (v/v/v) blend of pH4, 10-mM ammonium acetate buffer, methanol and 0.1% formic acid in Millipore water. The precision for both (R) and (S) sitagliptin phosphate varied between 0.246 and 1.246%, while the accuracy was 99.6-100.1%. A glucose uptake assay was used to assess enantiomers in 3T3-L1 cell lines through flow cytometry. Investigation of the pharmacokinetic impacts of sitagliptin phosphate racemic enantiomers in rat plasma revealed notable contrasts in R and S enantiomers in female albino Wistar rats, suggesting enantioselectivity for sitagliptin phosphate.
Topics: Rats; Female; Animals; Sitagliptin Phosphate; Chromatography, High Pressure Liquid; Rats, Wistar; Stereoisomerism; Methanol; Reproducibility of Results
PubMed: 37431826
DOI: 10.4155/bio-2023-0084 -
Clinical and Molecular Hepatology Sep 2018
Topics: Blood Glucose; Humans; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate; Synbiotics
PubMed: 30196651
DOI: 10.3350/cmh.2018.1006 -
BMJ Open Diabetes Research & Care Dec 2020The PIONEER 7 trial demonstrated superior glycemic control and weight loss with once-daily oral semaglutide with flexible dose adjustment versus sitagliptin 100 mg in... (Randomized Controlled Trial)
Randomized Controlled Trial
Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52-week, randomized, open-label extension of the PIONEER 7 trial.
INTRODUCTION
The PIONEER 7 trial demonstrated superior glycemic control and weight loss with once-daily oral semaglutide with flexible dose adjustment versus sitagliptin 100 mg in type 2 diabetes. This 52-week extension evaluated long-term oral semaglutide treatment and switching from sitagliptin to oral semaglutide.
RESEARCH DESIGN AND METHODS
A 52-week, open-label extension commenced after the 52-week main phase. Patients on oral semaglutide in the main phase continued treatment (n=184; durability part); those on sitagliptin were rerandomized to continued sitagliptin (n=98) or oral semaglutide (n=100; initiated at 3 mg) (switch part). Oral semaglutide was dose-adjusted (3, 7, or 14 mg) every 8 weeks based on glycated hemoglobin (HbA) (target <7.0% (<53 mmol/mol)) and tolerability. Secondary endpoints (no primary) included changes in HbA and body weight.
RESULTS
In the durability part, mean (SD) changes in HbA and body weight from week 0 were -1.5% (0.8) and -1.3% (1.0) and -2.8 kg (3.8) and -3.7 kg (5.2) at weeks 52 and 104, respectively. In the switch part, mean changes in HbA from week 52 to week 104 were -0.2% for oral semaglutide and 0.1% for sitagliptin (difference -0.3% (95% CI -0.6 to 0.0); p=0.0791 (superiority not confirmed)). More patients achieved HbA <7.0% with oral semaglutide (52.6%) than sitagliptin (28.6%; p=0.0011) and fewer received rescue medication (9% vs 23.5%). Respective mean changes in body weight were -2.4 kg and -0.9 kg (difference -1.5 kg (95% CI -2.8 to -0.1); p=0.0321). Gastrointestinal adverse events were the most commonly reported with oral semaglutide.
CONCLUSIONS
Long-term oral semaglutide with flexible dose adjustment maintained HbA reductions, with additional body weight reductions, and was well tolerated. Switching from sitagliptin to flexibly dosed oral semaglutide maintained HbA reductions, helped more patients achieve HbA targets with less use of additional glucose-lowering medication, and offers the potential for additional reductions in body weight.
TRIAL REGISTRATION NUMBER
NCT02849080.
Topics: Administration, Oral; Diabetes Mellitus, Type 2; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Sitagliptin Phosphate
PubMed: 33318068
DOI: 10.1136/bmjdrc-2020-001649 -
Expert Review of Cardiovascular Therapy Jun 2015Sitagliptin, a dipeptidyl peptidase 4 inhibitor, was the first in its class to receive approval from the US FDA in 2006 for the treatment of Type 2 diabetes mellitus. It... (Review)
Review
Sitagliptin, a dipeptidyl peptidase 4 inhibitor, was the first in its class to receive approval from the US FDA in 2006 for the treatment of Type 2 diabetes mellitus. It has been evaluated in numerous clinical trials and has several attractive features as an antidiabetic agent, including a low risk for hypoglycemia, a neutral effect on weight, and an ability to be used in chronic kidney disease and more. This article provides an up-to-date discussion of the pharmacokinetics/pharmacodynamics, clinical efficacy, safety and tolerability of sitagliptin.
Topics: Animals; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Approval; Humans; Hypoglycemia; Hypoglycemic Agents; Sitagliptin Phosphate; United States; United States Food and Drug Administration
PubMed: 26000559
DOI: 10.1586/14779072.2015.1046840 -
Journal of Environmental Science and... 2023Methotrexate (MTX), a cytotoxic chemotherapeutic and immunosuppressant agent, is widely used in the treatment of autoimmune diseases and different types of cancers....
Methotrexate (MTX), a cytotoxic chemotherapeutic and immunosuppressant agent, is widely used in the treatment of autoimmune diseases and different types of cancers. However, its use has been limited by its life-threatening side effects, including nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the protective effect of sitagliptin on methotrexate (MTX)-induced nephrotoxicity in rats. Twenty-four rats were divided into four groups: control group, which received the vehicle for 6 days; MTX group, which received a single dose of MTX, followed by five daily doses of vehicle dosing; MTX + sitagliptin group, which received a single dose of MTX 1 h after the first sitagliptin treatment and six daily doses of sitagliptin; and sitagliptin group, which received sitagliptin for 6 days. Both MTX and sitagliptin were given as intraperitoneal injections at a dose of 20 mg/kg body weight. All rats were euthanized on the seventh day of the study. Kidney tissues were harvested and blood samples were collected. Serum levels of blood urea nitrogen (BUN) and creatinine were evaluated. Furthermore, catalase, glutathione peroxidase, superoxide dismutase activities, and malondialdehyde (MDA) levels were determined in kidney tissue. In addition, histopathological analysis was conducted. Histopathological evaluation showed that MTX-induced marked kidney injury. Biochemical analysis revealed a significant increase of BUN and creatinine in the serum of the MTX group. Furthermore, oxidative stress and depressed antioxidant system of the kidney tissues were evident in the MTX group. Sitagliptin did not affect these endpoints when administered alone, but it significantly attenuated the observed MTX-induced effects. These results suggest that sitagliptin exhibits potent anti-oxidant properties against the nephrotoxicity induced by MTX in rats.
Topics: Rats; Animals; Methotrexate; Sitagliptin Phosphate; Creatinine; Antioxidants; Kidney; Renal Insufficiency
PubMed: 37010136
DOI: 10.1080/26896583.2023.2186683 -
Drugs in R&D Mar 2022Our objective was to evaluate the pharmacokinetics and bioequivalence of test and reference (JANUMET) formulations of sitagliptin phosphate/metformin hydrochloride... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Our objective was to evaluate the pharmacokinetics and bioequivalence of test and reference (JANUMET) formulations of sitagliptin phosphate/metformin hydrochloride tablets at a single dose of 50 mg/850 mg.
METHODS
The study was a randomized, open-label, two-period, double-crossover trial. Volunteers under fasting (n = 24) and fed (n = 24) conditions were given a single oral dose of test or reference formulations of sitagliptin phosphate/metformin hydrochloride tablets 50 mg/850 mg. We used the liquid chromatography tandem mass spectrometry method to determine the concentrations of sitagliptin and metformin in the plasma of subjects. Pharmacokinetic metrics were calculated using the WinNonlin 7.0 program, and bioequivalence was evaluated using SAS 9.4.
RESULTS
Under the fasting condition, the 90% confidence intervals (CIs) of geometric mean ratio for maximum plasma drug concentration (C), area under the plasma concentration-time curve from time zero to time t (AUC), and AUC from time zero to infinity (AUC) of sitagliptin between the test and reference groups were 101.70-120.62%, 99.81-105.61%, and 100.27-106.12%, respectively; for metformin, they were 90.39-111.48%, 94.76-109.12%, and 95.76-110.38%, respectively. Under the fed condition, they were 102.12-117.31%, 100.80-107.81%, and 100.82-107.78%, respectively, for sitagliptin and 95.53-105.22%, 92.76-103.07%, and 93.40-104.14%, respectively, for metformin. Both were generally well-tolerated.
CONCLUSION
The two formulations of sitagliptin phosphate/metformin hydrochloride tablets were bioequivalent under fasting and fed conditions in healthy Chinese subjects.
Topics: Area Under Curve; China; Cross-Over Studies; Fasting; Healthy Volunteers; Humans; Metformin; Sitagliptin Phosphate; Tablets; Therapeutic Equivalency
PubMed: 34850368
DOI: 10.1007/s40268-021-00371-2 -
Biochemical Pharmacology Aug 2023Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, is a risk factor for endothelial dysfunction, a common pathophysiological...
The effect of exenatide (a GLP-1 analogue) and sitagliptin (a DPP-4 inhibitor) on asymmetric dimethylarginine (ADMA) metabolism and selected biomarkers of cardiac fibrosis in rats with fructose-induced metabolic syndrome.
Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, is a risk factor for endothelial dysfunction, a common pathophysiological denominator for both atherogenesis and cardiac fibrosis. We aimed to investigate whether the cardioprotective and antifibrotic effects of incretin drugs, exenatide and sitagliptin, may be associated with their ability to affect circulating and cardiac ADMA metabolism. Normal and fructose-fed rats were treated with sitagliptin (5.0/10 mg/kg) or exenatide (5/10 µg/kg) for 4 weeks. The following methods were used: LC-MS/MS, ELISA, Real-Time-PCR, colorimetry, IHC and H&E staining, PCA and OPLS-DA projections. Eight-week fructose feeding resulted in an increase in plasma ADMA and a decrease in NO concentration. Exenatide administration into fructose-fed rats reduced the plasma ADMA level and increased NO level. In the heart of these animals exenatide administration increased NO and PRMT1 level, reduced TGF-ß1, α-SMA levels and COL1A1 expression. In the exenatide treated rats renal DDAH activity positively correlated with plasma NO level and negatively with plasma ADMA level and cardiac α-SMA concentration. Sitagliptin treatment of fructose-fed rats increased plasma NO concentration, reduced circulating SDMA level, increased renal DDAH activity and reduced myocardial DDAH activity. Both drugs attenuated the myocardial immunoexpression of Smad2/3/P and perivascular fibrosis. In the metabolic syndrome condition both sitagliptin and exenatide positively modulated cardiac fibrotic remodeling and circulating level of endogenous NOS inhibitors but had no effects on ADMA levels in the myocardium.
Topics: Rats; Animals; Sitagliptin Phosphate; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Metabolic Syndrome; Fructose; Chromatography, Liquid; Tandem Mass Spectrometry; Hypoglycemic Agents; Fibrosis; Arginine; Protease Inhibitors; Biomarkers; Glucagon-Like Peptide 1; Amidohydrolases; Nitric Oxide
PubMed: 37290595
DOI: 10.1016/j.bcp.2023.115637