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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 -
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 -
Pakistan Journal of Pharmaceutical... Nov 2016Obesity, dyslipidemia and hypertension are major risk factors for cardiovascular disease and its associated complications. To evaluate the beneficial effects of... (Randomized Controlled Trial)
Randomized Controlled Trial
Obesity, dyslipidemia and hypertension are major risk factors for cardiovascular disease and its associated complications. To evaluate the beneficial effects of sitagliptin and metformin in non-diabetic dyslipidemic and hypertensive patients. A prospective randomized clinical trial was conducted on 70 newly diagnosed dyslipidemic patients with BMI > 25 and blood pressure > 130/80 at outpatient clinic of medical unit-1 of Sheikh Medical College/Hospital, Rahim Yar Khan. They were divided in to three groups each containing 35 patients; First group served as a healthy control while second and third study groups were given tablet sitagliptin 50mg and tab metformin 850mg respectively twice a day for twelve weeks. After three months treatment with sitagliptin and metformin there was significant reduction in body weight (Sitagliptin 6.5% vs Metformin 7.65%) and BMI (Sitagliptin 2.2% vs Metformin 2.8%) with p <0.05. Metformin caused a significant reduction in blood pressure with p < 0.05 (i.e. SBP 9.9% & DBP 6.4%) while sitagliptin caused a highly significant p <0.01 reduction in blood pressure (i.e. SBP 15.8% & DBP 12.2%). There was significant improvement in lipid profile with sitagliptin p<0.05. The percent reduction in value of TC, TG and LDL-C was 20.2%, 13.8% and 23.7% while HDL-C value was increased 11.2% respectively. There was highly significant improvement in lipid profile with metformin p<0.01. The percent reduction in value of TC, TG and LDL-C was 27.8%, 28.2% and 40.4% while HDL-C value was increased 16.8% respectively. Both drugs improve cardiometabolic risk factors independently in non-diabetic patients.
Topics: Adult; Antihypertensive Agents; Biomarkers; Blood Pressure; Dipeptidyl-Peptidase IV Inhibitors; Dyslipidemias; Female; Humans; Hypertension; Hypolipidemic Agents; Lipids; Male; Metformin; Middle Aged; Pakistan; Prospective Studies; Sitagliptin Phosphate; Time Factors; Treatment Outcome; Weight Loss
PubMed: 28167482
DOI: No ID Found -
Molecular and Cellular Endocrinology Jan 2023We recently demonstrated that combined therapy of GABA and sitagliptin promoted beta-cell proliferation, and decreased beta-cell apoptosis in a multiple low-dose...
We recently demonstrated that combined therapy of GABA and sitagliptin promoted beta-cell proliferation, and decreased beta-cell apoptosis in a multiple low-dose streptozotocin (STZ)-induced beta-cell injury mouse model. In this study, we examined whether this combined therapy is effective in ameliorating the impairment of beta-cell function caused by high-fat diet (HFD) feeding in mice. Male C57BL/6J mice were fed normal chow diet, HFD, or HFD combined with GABA, sitagliptin, or both drugs. Oral drug daily administration was initiated one week before HFD and maintained for two weeks. After two weeks of intervention, we found that GABA or sitagliptin administration ameliorated the impairment of glucose tolerance induced by HFD. This was associated with improved insulin secretion in vivo. Notably, combined administration of GABA and sitagliptin significantly enhanced these effects as compared to each of the monotherapies. Combined GABA and sitagliptin was superior at increasing beta-cell mass, and associated Ki67 and PDX-1 beta-cell counts. In addition, we found that HFD-induced compensatory beta-cell proliferation was associated with increased activation of unfolded protein response (UPR), as indicated by BiP expression. This could be an important mechanism of compensatory beta-cell proliferation, and beta cells treated with GABA and sitagliptin showed greater UPR activation. Our results suggest that the combined use of these agents produces superior therapeutic outcomes.
Topics: Male; Mice; Animals; Mice, Inbred C57BL; Sitagliptin Phosphate; Diet, High-Fat; Streptozocin; Multiple Trauma; gamma-Aminobutyric Acid
PubMed: 36049597
DOI: 10.1016/j.mce.2022.111755 -
Diabetes, Obesity & Metabolism Apr 2018The present study was a 4-week randomized trial to assess the efficacy and safety of sitagliptin, a dipeptidyl-peptidase-4 inhibitor, in persistent or recurring type 2... (Randomized Controlled Trial)
Randomized Controlled Trial
The present study was a 4-week randomized trial to assess the efficacy and safety of sitagliptin, a dipeptidyl-peptidase-4 inhibitor, in persistent or recurring type 2 diabetes after Roux-en-Y gastric bypass surgery (RYGB). Participants (n = 32) completed a mixed meal test (MMT) and self-monitoring of plasma glucose (SMPG) before and 4 weeks after randomization to either sitagliptin 100 mg daily or placebo daily. Questionnaires were administered to assess gastrointestinal discomfort. Outcome variables were glucose, active glucagon-like peptide-1 and β-cell function during the MMT, and glucose levels during SMPG. Age (56.3 ± 8.2 years), body mass index (34.4 ± 6.7 kg/m ), glycated haemoglobin (7.21 ± 0.77%), diabetes duration (12.9 ± 10.0 years), years since RYGB (5.6 ± 3.3 years) and β-cell function did not differ between the placebo and sitagliptin groups at pre-intervention. Sitagliptin was well tolerated, decreased postprandial glucose levels during the MMT (from 8.31 ± 1.92 mmol/L to 7.67 ± 1.59 mmol/L, P = 0.03) and mean SMPG levels, but had no effect on β-cell function. In patients with diabetes and mild hyperglycemia after RYGB, a short course of sitagliptin provided a small but significant glucose-lowering effect, with no identified improvement in β-cell function.
Topics: Adult; Aged; Blood Glucose; Combined Modality Therapy; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glycated Hemoglobin; Humans; Longitudinal Studies; Male; Middle Aged; Sitagliptin Phosphate
PubMed: 29072800
DOI: 10.1111/dom.13139 -
Bioengineered Jan 2022Sitagliptin is a well-established anti-diabetic drug that also exerts protective effects on diabetic complications. Previous work reveals that sitagliptin has a...
Sitagliptin is a well-established anti-diabetic drug that also exerts protective effects on diabetic complications. Previous work reveals that sitagliptin has a protective effect on diabetic nephropathy (DN). Vascular impairment frequently occurs in diabetic renal complications. Here, we evaluated the protective function of sitagliptin in human renal glomerular endothelial cells (HrGECs) under high glucose (HG) conditions. Expressions of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-8 (IL-8) were assessed using real-time PCR and ELISA. Endothelial cells permeability was assayed using the fluorescein isothiocyanate dextran (FITC-dextran) and trans-endothelial electrical resistance (TEER) assay. The results show that sitagliptin mitigated HG-induced oxidative stress in HrGECs with decreased levels of mitochondrial reactive oxygen species (ROS), Malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG). Sitagliptin inhibited HG-induced production of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-8 (IL-8) in HrGECs. It also ameliorated HG-induced aggravation of HrGECs permeability and reduction of the tight junction component claudin-5. Moreover, kruppel Like Factor 6 (KLF6) mediated the protective effects of sitagliptin on endothelial monolayer permeability against HG. Collectively, sitagliptin reversed the HG-induced oxidative stress, inflammation, and increased permeability in HrGECs via regulating KLF6. This study suggests that sitagliptin might be implicated as an effective strategy for preventing diabetic renal injuries in the future.
Topics: Cell Line; Diabetic Nephropathies; Endothelial Cells; Glucose; Humans; Inflammation; Kidney Glomerulus; Oxidative Stress; Sitagliptin Phosphate
PubMed: 34967261
DOI: 10.1080/21655979.2021.2012550 -
JAMA Apr 2019
Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Metformin; Sitagliptin Phosphate
PubMed: 30903797
DOI: 10.1001/jama.2019.2941 -
International Journal of Biological... Aug 2023Highly mutated SARS-CoV-2 is known aetiological factor for COVID-19. Here, we have demonstrated that the receptor binding domain (RBD) of the spike protein can interact...
Highly mutated SARS-CoV-2 is known aetiological factor for COVID-19. Here, we have demonstrated that the receptor binding domain (RBD) of the spike protein can interact with human dipeptidyl peptidase 4 (DPP4) to facilitate virus entry, in addition to the usual route of ACE2-RBD binding. Significant number of residues of RBD makes hydrogen bonds and hydrophobic interactions with α/β-hydrolase domain of DPP4. With this observation, we created a strategy to combat COVID-19 by circumventing the catalytic activity of DPP4 using its inhibitors. Sitagliptin, linagliptin or in combination disavowed RBD to establish a heterodimer complex with both DPP4 and ACE2 which is requisite strategy for virus entry into the cells. Both gliptins not only impede DPP4 activity, but also prevent ACE2-RBD interaction, crucial for virus growth. Sitagliptin, and linagliptin alone or in combination have avidity to impede the growth of pan-SARS-CoV-2 variants including original SARS-CoV-2, alpha, beta, delta, and kappa in a dose dependent manner. However, these drugs were unable to alter enzymatic activity of PLpro and Mpro. We conclude that viruses hijack DPP4 for cell invasion via RBD binding. Impeding RBD interaction with both DPP4 and ACE2 selectively by sitagliptin and linagliptin is an potential strategy for efficiently preventing viral replication.
Topics: Humans; COVID-19; Linagliptin; SARS-CoV-2; Sitagliptin Phosphate; Dipeptidyl Peptidase 4; Angiotensin-Converting Enzyme 2; Protein Binding
PubMed: 37385308
DOI: 10.1016/j.ijbiomac.2023.125444 -
Current Molecular Pharmacology 2022In coronavirus disease 2019 (Covid-19), SARS-CoV-2 may use dipeptidyl peptidase 4 (DPP4) as an entry-point in different tissues expressing these receptors. DPP4...
OBJECTIVES
In coronavirus disease 2019 (Covid-19), SARS-CoV-2 may use dipeptidyl peptidase 4 (DPP4) as an entry-point in different tissues expressing these receptors. DPP4 inhibitors (DPP4Is), also named gliptins, like sitagliptin, have anti-inflammatory and antioxidant effects, thereby lessen inflammatory and oxidative stress in diabetic Covid-19 patients. Therefore, the present study aimed to illustrate the potential beneficial effect of sitagliptin in managing Covid-19 in non-diabetic patients.
METHODS
A total number of 89 patients with Covid-19 were recruited from a single center at the time of diagnosis. The recruited patients were assigned according to the standard therapy for Covid-19 and our interventional therapy into two groups; Group A: Covid-19 patients on the standard therapy (n=40) and Group B: Covid-19 patients on the standard therapy plus sitagliptin (n=49). The duration of this interventional study was 28 days according to the guideline in managing patients with Covid-19. Routine laboratory investigations, serological tests, Complete Blood Count (CBC), C-reactive Protein (CRP), D-dimer, lactate dehydrogenase (LDH), and serum ferritin were measured to observed Covid-19 severity and complications. Lung Computed Tomography (CT) and clinical scores were evaluated.
RESULTS
The present study illustrated that sitagliptin as an add-on to standard therapy improved clinical outcomes, radiological scores, and inflammatory biomarkers than standard therapy alone in non-diabetic patients with Covid-19 (P<0.01).
CONCLUSION
Sitagliptin as an add-on to standard therapy in managing non-diabetic Covid-19 patients may have a robust beneficial effect by modulating inflammatory cytokines with subsequent good clinical outcomes.
Topics: Diabetes Mellitus; Dipeptidyl-Peptidase IV Inhibitors; Humans; SARS-CoV-2; Sitagliptin Phosphate; COVID-19 Drug Treatment
PubMed: 34477540
DOI: 10.2174/1874467214666210902115650 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Sep 2021To investigate the effects of Sitagliptin on myocardial remodeling and autophagy in diabetic mice and its possible mechanisms. C57 mice aged ten weeks were treated...
To investigate the effects of Sitagliptin on myocardial remodeling and autophagy in diabetic mice and its possible mechanisms. C57 mice aged ten weeks were treated with streptozocin (STZ) at the dose of 50 mg/(kg·d) by intraperitoneal injections for five consecutive days, and the level of fasting blood glucose concentration was higher than 16.7 mmol/l after seven days indicated that the diabetic model was established successfully. Mice were divided into four groups, including control group (=10) which was intraperitoneally injected with the same volum of saline, the model group (=8), Sitagliptin treatment group(diabetic mice were treated with Sitagliptin at the dose of 10 mg/(kg·d)by gavage, =8) and the inhibitor group(diabetic mice were treated with Compound C, an AMPK inhibitor, at the dose of 10 mg/(kg·d) by intraperitoneal injection, =8). After six weeks, all the mices were weighted and then put to death and the hearts were separated to caculate ventricular /body weight ratio. Hemaloxylin-Eosin (HE) staining was used to observe the cell morphology and masson staining was used to observe interstitial fibrosis. Western blot was used to test the heart protein expressions of Connexin43(Cx43), adenosine 5'-monophosphate -activated protein kinase (AMPK), brain natriuretic peptide(BNP), transforming growth factor(TGF-β) and LC3B. After six weeks of treatment, compared with control group, the ventricular /body weight ratio was improved (<0.05), The cardiomyocyte hypertrophy and increased fibrosis were observed in the model group. The expression levels of BNP and TGF-β were increased, while the expression levels of Cx43,LC3B and AMPK were decreased significantly(<0.05). However, compared with model group, treatment with Sitagliptin decreased BNP, TGF-β protein levels and increased Cx43 and LC3B protein levels, while Compound C could inhibit the upregulation of Cx43, LC3B and AMPK protein (<0.05). Sitagliptin could improve cardiac hypertrophy and decrease interstitial fibrosis and AMPK-related signaling pathways was involved in the regulation of Cx43 and autophagy.
Topics: Animals; Autophagy; Diabetes Mellitus, Experimental; Mice; Myocardium; Sitagliptin Phosphate; Streptozocin
PubMed: 34816668
DOI: 10.12047/j.cjap.6129.2021.073