-
Biomolecules Jan 2023Cholesterol efflux is a major atheroprotective function of high-density lipoproteins (HDLs) which removes cholesterol from the foam cells of lipid-rich plaques in Type 2...
Cholesterol efflux is a major atheroprotective function of high-density lipoproteins (HDLs) which removes cholesterol from the foam cells of lipid-rich plaques in Type 2 diabetes. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin phosphate increases plasma glucagon-like peptide-1 (GLP-1) concentrations and is used to treat Type 2 diabetes. GLP-1 plays an important role in regulating insulin secretion and expression via the GLP-1 receptor (GLP-1R), which is expressed in pancreatic islets as well as freshly isolated human monocytes and THP-1 cells. Here, we identified a direct role of GLP-1 and DPP-4 inhibition in HDL function. Cholesterol efflux was measured in cultivated phorbol 12-myristate 13-acetate-treated THP-1 cells radiolabeled with H-cholesterol and stimulated with liver X receptor/retinoid X receptor agonists. Contrary to vildagliptin, sitagliptin phosphate together with GLP-1 significantly ( < 0.01) elevated apolipoprotein (apo)A1-mediated cholesterol efflux in a dose-dependent manner. The sitagliptin-induced increase in cholesterol efflux did not occur in the absence of GLP-1. In contrast, adenosine triphosphate-binding cassette transporter A1 (ABCA1) mRNA and protein expressions in the whole cell fraction were not changed by sitagliptin in the presence of GLP-1, although sitagliptin treatment significantly increased ABCA1 protein expression in the membrane fraction. Furthermore, the sitagliptin-induced, elevated efflux in the presence of GLP-1 was significantly decreased by a GLP-1R antagonist, an effect that was not observed with a protein kinase A inhibitor. To our knowledge, the present study reports for the first time that sitagliptin elevates cholesterol efflux in cultivated macrophages and may exert anti-atherosclerotic actions that are independent of improvements in glucose metabolism. Our results suggest that sitagliptin enhances HDL function by inducing a de novo HDL synthesis via cholesterol efflux.
Topics: Humans; Sitagliptin Phosphate; Dipeptidyl-Peptidase IV Inhibitors; Diabetes Mellitus, Type 2; THP-1 Cells; Hypoglycemic Agents; Glucagon-Like Peptide 1; Cholesterol; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
PubMed: 36830597
DOI: 10.3390/biom13020228 -
Diabetes Research and Clinical Practice Jan 2022To evaluate glycemic variations, changes in insulin resistance and oxidative stress after chiglitazar or sitagliptin treatment in untreated patients with type 2 diabetes... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
RESULTS
After treatment for 24 weeks, our data showed a similar reduction in HbA1c between chiglitazar and sitagliptin. The 24-h mean blood glucose (MBG), standard deviation (SD) and mean amplitude of glycemic excursion (MAGE) were significantly decreased, and the time in range (TIR) was increased after chiglitazar and sitagliptin therapy. Chiglitazar administration led to significant improvement in insulin resistance/insulin secretion (HOMA-IR, HOMA-IS), interleukin-6 (IL-6), prostaglandin F2α (PGF-2α), 17-hydroxyprogesterone (17-OHP) and adiponectin (ADP) score values compared with sitagliptin administration.
CONCLUSIONS
Chiglitazar therapy effectively reduced glucose variation and showed a larger improvement in insulin resistance and inflammatory parameters than sitagliptin.
Topics: Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Carbazoles; Diabetes Mellitus, Type 2; Glucose; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Resistance; Propionates; Sitagliptin Phosphate
PubMed: 34883184
DOI: 10.1016/j.diabres.2021.109171 -
European Review For Medical and... Nov 2021Diabetes mellitus is a chronic metabolic disease which has an adverse impact on the quality of patient's life, so patients often need to receive treatment for a long... (Clinical Trial)
Clinical Trial Comparative Study
OBJECTIVE
Diabetes mellitus is a chronic metabolic disease which has an adverse impact on the quality of patient's life, so patients often need to receive treatment for a long time. Selection of medications with high therapeutics effects and low cost is very important for patients to take medicine for a longer period of time. Sitagliptin is a drug which is widely used in clinics and can effectively control blood glucose level. This article explores the pharmacoeconomic value of Sitagliptin in the treatment of diabetes mellitus.
PATIENTS AND METHODS
A total of 100 patients with diabetes mellitus treated were recruited in this study. The patients were randomly divided into 4 groups with 25 cases in each group. Patients in group A were treated with pioglitazone, group B with Sitagliptin, group C with metformin and group D with glimepiride. The cost of the drugs, the treatment results and adverse effects were compared.
RESULTS
Compared with group A, C and D, the cost-effectiveness ratio of group B was low (p<0.05), and the therapeutic effect was high (p<0.05). In addition, the incidence of adverse reactions in group B was lower than that in group A, C and D (p<0.05). There was no significant difference in the levels of FPG, 2hPG and HbAlc in patients among the four groups before treatment (p>0.05). After treatment, the levels of FPG, 2hPG and HbAlc in group B were significantly lower than those in groups A, C and D (p<0.05). Finally, there was no significant difference in waist circumference and BMI among the four groups before treatment (p>0.05). After treatment, the waist circumference and BMI in group B were lower than those in groups A, C and D (p<0.05).
CONCLUSIONS
The application of Sitagliptin in the treatment of diabetic patients can effectively enhance the therapeutic effect. The cost effectiveness is satisfactory, and the blood glucose level can be maintained at a stable state.
Topics: Adult; Aged; Aged, 80 and over; Cost-Benefit Analysis; Diabetes Mellitus; Economics, Pharmaceutical; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Pioglitazone; Sitagliptin Phosphate; Sulfonylurea Compounds
PubMed: 34859870
DOI: 10.26355/eurrev_202111_27258 -
Journal of Atherosclerosis and... Jan 2022
Topics: Atherosclerosis; Cholesterol, LDL; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Proprotein Convertase 9; Pyrimidines; Sitagliptin Phosphate
PubMed: 33612709
DOI: 10.5551/jat.ED164 -
Reproductive Sciences (Thousand Oaks,... Apr 2023To evaluate the effects of sitagliptin on the metabolic indices and hormone levels in patients with polycystic ovary syndrome (PCOS). PubMed, EMBASE, Web of Science,... (Meta-Analysis)
Meta-Analysis Review
To evaluate the effects of sitagliptin on the metabolic indices and hormone levels in patients with polycystic ovary syndrome (PCOS). PubMed, EMBASE, Web of Science, Cochrane Library, WanFang Data, and China National Knowledge Infrastructure (CNKI) were searched for randomized controlled trials (RCTs) published up to March 2022. Eligible studies were identified based on the inclusion criteria. The primary outcomes included the homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), and total testosterone level (TT). Other outcomes included levels of sex hormones, glucose, and lipid metabolism. Forty-five studies were initially identified, and 6 RCTs with 394 patients were finally included in this study. The meta-analysis results suggest that sitagliptin improved HOMA-IR (WMD = - 0.35; 95% CI (- 0.62, - 0.08); P = 0.01), BMI (WMD = - 1.27; 95% CI (- 1.76, - 0.77); P < 0.00001), TT (SMD = - 0.66; 95% CI (- 1.25, - 0.07); P = 0.03), and HDL-C (SMD = 0.11; 95% CI (0.03, 0.18); P = 0.005). No significant differences were observed between the sitagliptin and control groups in other outcomes and in terms of adverse events. Evidence from meta-analyses suggests that sitagliptin was superior in improving insulin sensitivity, total serum testosterone, high-density lipoprotein, and body mass index. However, due to the limitations of published studies, it is difficult to draw a definite conclusion. Larger, higher-quality studies are needed to evaluate the efficacy of sitagliptin in women with PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Sitagliptin Phosphate; Randomized Controlled Trials as Topic; Insulin Resistance; Testosterone
PubMed: 35962305
DOI: 10.1007/s43032-022-01061-3 -
Pharmaceutical Development and... Jul 2022Direct compression (DC) is the simplest and most economical way to produce pharmaceutical tablets. Ideally, it consists of only two steps: dry blending of a drug...
Direct compression (DC) is the simplest and most economical way to produce pharmaceutical tablets. Ideally, it consists of only two steps: dry blending of a drug substance(s) with excipients followed by compressing the powder mixture into tablets. In this study, immediate-release film-coated tablets containing either Sitagliptin phosphate or Sitagliptin hydrochloride were developed using DC technique. After establishing the optimum ratio of ductile and brittle excipients, five formulations were compressed into tablets using a rotary press and finally film coated. Both powders and tablets were examined by standard pharmacopoeial methods. It has been shown that the simultaneous use of excipients with different physical properties, i.e. ductile microcrystalline cellulose and brittle anhydrous dibasic calcium phosphate, produces a synergistic effect, allowing preparation of Sitagliptin DC tablets with good mechanical strength (tensile strength over 2 N/mm), rapid disintegration (shorter than 2 min), and fast release of the drug substance (85% of the drug is dissolved within 15 min). It was found that the type of calcium phosphate excipient used had a large effect on the properties of the sitagliptin tablets. All formulations developed showed good chemical stability, even when stored under stress conditions (50 °C/80% RH).
Topics: Calcium Phosphates; Drug Compounding; Excipients; Plastics; Powders; Sitagliptin Phosphate; Tablets; Tensile Strength
PubMed: 35913021
DOI: 10.1080/10837450.2022.2107013 -
Irish Journal of Medical Science May 2021Insulin resistance plays a major role in the pathogenesis of polycystic ovary syndrome (PCOS). Therefore, there is a growing interest in the use of insulin sensitizer...
BACKGROUND
Insulin resistance plays a major role in the pathogenesis of polycystic ovary syndrome (PCOS). Therefore, there is a growing interest in the use of insulin sensitizer drugs in the treatment of PCOS. Research in recent years has shown that sitagliptin has been reported to improve ovarian cycles and ovulation in PCOS patients.
AIMS
We aimed to compare the effects of metformin and sitagliptin on PCOS individuals undergoing ICSI.
METHODS
Sixty PCOS patients were divided into 3 groups: metformin, sitagliptin, and placebo group. Treatment was carried out 2 months before the start of the ovulation cycle and continued until the day of oocyte aspiration. The serum levels of total testosterone, estradiol, and fasting insulin along with the total number of retrieved, normal and abnormal MII, and fertilized oocytes, the number of transferred embryos (grades I, II and III), and biochemical and clinical pregnancy rates as well as the ovarian hyperstimulation syndrome (OHSS) were evaluated.
RESULTS
There was a significant reduction in the serum levels of Insulin and total testosterone in the treated groups compared with the placebo. The number of mature and normal MII oocytes increased significantly in the treated groups compared with the placebo. Moreover, the number of immature oocytes decreased significantly and the number of grade I embryos increases significantly in the sitagliptin group compared with the placebo group.
CONCLUSION
We conclude that sitagliptin can improve the maturation of oocytes and embryos' quality more effectively than metformin, in PCOS patients undergoing ICSI.
TRIAL REGISTRATION
Trial registration is NCT04268563 ( https://clinicaltrials.gov ).
Topics: Adult; Female; Humans; Metformin; Oocytes; Polycystic Ovary Syndrome; Sitagliptin Phosphate; Sperm Injections, Intracytoplasmic
PubMed: 32720198
DOI: 10.1007/s11845-020-02320-5 -
Inflammopharmacology Dec 2022Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome type 2 (SARS-CoV-2). Covid-19 is characterized by hyperinflammation, oxidative stress,... (Review)
Review
Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome type 2 (SARS-CoV-2). Covid-19 is characterized by hyperinflammation, oxidative stress, and multi-organ injury (MOI) such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Covid-19 is mainly presented with respiratory manifestations; however, extra-pulmonary manifestations may also occur. Extra-pulmonary manifestations of Covid-19 are numerous including: neurological, cardiovascular, renal, endocrine, and hematological complications. Notably, a cluster of differentiation 26 (CD26) or dipeptidyl peptidase-4 (DPP-4) emerged as a new receptor for entry of SARS-CoV-2. Therefore, DPP-4 inhibitors like sitagliptin could be effective in treating Covid-19. Hence, we aimed in the present critical review to assess the potential role of sitagliptin in Covid-19. DPP-4 inhibitors are effective against the increased severity of SARS-CoV-2 infections. Moreover, DPP-4 inhibitors inhibit the interaction between DPP-4 and scaffolding proteins which are essential for endosome formation and replication of SARS-CoV-2. Therefore, sitagliptin through attenuation of the inflammatory signaling pathway and augmentation of stromal-derived factor-1 (SDF-1) may decrease the pathogenesis of SARS-CoV-2 infection and could be a possible therapeutic modality in treating Covid-19 patients. In conclusion, the DPP-4 receptor is regarded as a potential receptor for the binding and entry of SARS-CoV-2. Inhibition of these receptors by the DPP-4 inhibitor, sitagliptin, can reduce the pathogenesis of the infection caused by SARS-CoV-2 and their associated activation of the inflammatory signaling pathways.
Topics: Humans; SARS-CoV-2; Sitagliptin Phosphate; Dipeptidyl-Peptidase IV Inhibitors; Lung; COVID-19 Drug Treatment
PubMed: 36180664
DOI: 10.1007/s10787-022-01078-9 -
International Journal of Clinical... Mar 2023Various studies have reported the association of cognition and depression with diabetes. Literature suggests that metformin and sitagliptin used to control hyperglycemia... (Observational Study)
Observational Study
BACKGROUND
Various studies have reported the association of cognition and depression with diabetes. Literature suggests that metformin and sitagliptin used to control hyperglycemia in type 2 diabetes mellitus (T2DM) possess a beneficial effect on neurological symptoms associated with diabetes. However, there are scarce data in the clinical setting. Thus, this study aims to compare depression, cognitive impairment, and quality of life (QoL) of newly diagnosed T2DM patients with those of healthy individuals. Further, the impact of metformin alone or in combination with dipeptidyl peptidase-4 inhibitors on cognition, depression, and QoL of T2DM patients was also compared with newly diagnosed T2DM patients.
MATERIALS AND METHODS
This was a prospective observational study in 120 subjects. The subjects were equally divided into four groups: healthy controls, newly diagnosed T2DM patients, and T2DM patients taking either metformin alone or in combination with sitagliptin. We assessed cognition using Mini-Mental State Examinations (MMSE), depression using Hamilton Depression Rating Scale (HAM-D), and health status using Short-Form Health Survey-36 (SF-36).
RESULTS
No significant change in MMSE score was observed among the groups. However, a significant increase in the HAM-D score of newly diagnosed patients (p < 0.001), T2DM patients receiving metformin alone (p < 0.05), and in combination with sitagliptin (p < 0.001) was observed as compared to healthy controls (p < 0.001). Also, a statistically significant increase in HAM-D score was observed in patients receiving sitagliptin in combination with metformin as compared to metformin alone (p < 0.01). A decrease in SF-36 scores was observed in all groups as compared to healthy controls.
CONCLUSION
To conclude, this preliminary study indicates that T2DM patients are most likely to suffer from depression and impaired QoL. Moreover, both the conventional and recent antidiabetic agents might lead to neurobehavioral complications and adverse impact on the QoL of these patients. Thus, we warrant the assessment of cognitive functions, depression, and QoL in patients receiving metformin and sitagliptin.
Topics: Humans; Sitagliptin Phosphate; Diabetes Mellitus, Type 2; Metformin; Quality of Life; Depression; Glycated Hemoglobin; Hypoglycemic Agents; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Blood Glucose
PubMed: 36519927
DOI: 10.5414/CP204288 -
Biochimica Et Biophysica Acta.... Aug 2022Autoimmune-led challenge resulting in β-cell loss is responsible for the development of type 1 diabetes (T1D). Melatonin, a pineal hormone or sitagliptin, a dipeptidyl...
Autoimmune-led challenge resulting in β-cell loss is responsible for the development of type 1 diabetes (T1D). Melatonin, a pineal hormone or sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, has increased β-cell mass in various diabetic models and has immunoregulatory property. Both β-cell regenerative capacity and melatonin secretion decrease with ageing. Thus, we aimed to investigate the therapeutic potential of melatonin combined with sitagliptin on β-cell regeneration under glucotoxic stress, in the streptozotocin-induced young and old diabetic mouse models, and euglycemic humanized islet transplant mouse model. Our results suggest that combination therapy of sitagliptin and melatonin show an additive effect in inducing mouse β-cell regeneration under glucotoxic stress, and in the human islet transplant mouse model. Further, in the young diabetic mouse model, the monotherapies induce β-cell transdifferentiation and reduce β-cell apoptosis whereas, in the old diabetic mouse model, melatonin and sitagliptin induce β-cell proliferation and β-cell transdifferentiation, and it also reduces β-cell apoptosis. Further, in both the models, combination therapy reduces fasting blood glucose levels, increases plasma insulin levels and glucose tolerance and promotes β-cell proliferation, β-cell transdifferentiation, and reduces β-cell apoptosis. It can be concluded that combination therapy is superior to monotherapies in ameliorating diabetic manifestations, and it can be used as a future therapy for β-cell regeneration in diabetes patients.
Topics: Animals; Blood Glucose; Diabetes Mellitus; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Humans; Hypoglycemic Agents; Melatonin; Mice; Pyrazines; Sitagliptin Phosphate; Triazoles
PubMed: 35364117
DOI: 10.1016/j.bbamcr.2022.119263