Use Of Sitagliptin Research Articles

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with alpha-glucosidase inhibitor in Japanese patients with type2 diabetes inadequately controlled on metformin or pioglitazone alone (Study for an Ultimate Combination Therapy to Control Diabetes with Sitagliptin-1): A multicenter, randomized, open-label, non-inferiority trial.

Aims/IntroductionTo assess the efficacy and safety of sitagliptin compared with α-glucosidase inhibitors in Japanese patients with type 2 diabetes inadequately controlled by metformin or pioglitazone alone.Materials and MethodsIn the present multicenter, randomized, open-label, parallel-group, active-controlled, non-inferiority trial, 119 patients aged 20–79 years with type 2 diabetes who had glycated hemoglobin 6.9–8.8% on stable metformin (500–1,500 mg/day) or pioglitazone (15–30 mg/day) alone were randomly assigned (1:1) to receive the addition of sitagliptin (50 mg/day) or an α-glucosidase inhibitor (0.6 mg/day voglibose or 150 mg/day miglitol) for 24 weeks. The primary end-point was change in glycated hemoglobin from baseline to week 12. All data were analyzed according to the intention-to-treat principle.ResultsAfter 12 weeks, reductions in adjusted mean glycated hemoglobin from baseline were −0.70% in sitagliptin and −0.21% in the α-glucosidase inhibitor groups respectively; between-group difference was −0.49% (95% confidence interval −0.66 to −0.32, P < 0.0001), meeting the predefined non-inferiority criterion (0.25%) and showing statistical significance. This statistical significance also continued after 24 weeks. Although sitagliptin did not affect bodyweight, α-glucosidase inhibitors decreased bodyweight significantly from baseline (−0.39 kg; P = 0.0079). Gastrointestinal disorders were significantly lower with sitagliptin than with an α-glucosidase inhibitor (6 [10.3%] patients vs 23 [39.7%]; P = 0.0003). Minor hypoglycemia occurred in two patients (3.5%) in each group.ConclusionsSitagliptin showed greater efficacy and better tolerability than an α-glucosidase inhibitor when added to stable doses of metformin or pioglitazone. These findings support the use of sitagliptin in Japanese patients with type 2 diabetes inadequately controlled by insulin-sensitizing agents. This trial was registered with UMIN (no. 000004675).

One year remission of type 1 diabetes mellitus in a patient treated with sitagliptin.

SummaryType 1 diabetes mellitus (T1DM) is a chronic disease characterized by the autoimmune destruction of pancreatic β-cells. This paper describes the case of a 19-year-old male patient who presented with glutamic acid decarboxylase (GAD) antibody positive and diabetic ketoacidosis, which mandated intensive insulin treatment. Once the ketoacidosis was controlled, an oral dose of 100 mg of sitagliptin was administered once a day. Ketoacidosis was managed by insulin and insulin daily requirement began to dwindle after one month, until its complete withdrawal at 8 weeks, when partial remission was reached. The patient has now remained on sitagliptin treatment alone for a year, without requiring insulin. The benefit observed with this medication is possibly associated with its immunological effects. Inhibition of dipeptidyl peptidase 4 in animal models deregulates the Th1 immune response, increases secretion of Th2 cytokines, activates CD4+CD25+FoxP3+ regulatory T-cells, and prevents IL17 production.Learning points The use of insulin-dose-adjusted HbA1c constitutes the best way to define partial remission in T1DM patients.The use of sitagliptin in T1DM patients could help to decrease daily requirement of insulin by delaying β-cell loss and improving endogenous insulin production.The determination of antibodies against insulin, islet cells, and GAD permits differentiation of T1DM patients from those with atypical or ketosis-prone diabetes.

Dipeptidyl-peptidase 4 inhibition and the vascular effects of glucagon-like peptide-1 and brain natriuretic peptide in the human forearm.

BackgroundDipeptidyl‐peptidase 4 (DPP4) inhibitors improve glycemic control in patients with diabetes mellitus by preventing the degradation of glucagon‐like peptide‐1 (GLP‐1). GLP‐1 causes vasodilation in animal models but also increases sympathetic activity; the effect of GLP‐1 in the human vasculature and how it is altered by DPP4 inhibition is not known. DPP4 also degrades the vasodilator brain natriuretic peptide (BNP) to a less potent metabolite. This study tested the hypothesis that DPP4 inhibition potentiates the vasodilator responses to GLP‐1 and BNP in the human forearm.Method and ResultsSeventeen healthy subjects participated in this randomized, double‐blinded, placebo‐controlled crossover study. On each study day, subjects received DPP4 inhibitor (sitagliptin 200 mg by mouth) or placebo. Sitagliptin increased forearm blood flow and decreased forearm vascular resistance without affecting mean arterial pressure and pulse. GLP‐1 and BNP were infused in incremental doses via brachial artery. Venous GLP‐1 concentrations were significantly higher during sitagliptin use, yet there was no effect of GLP‐1 on forearm blood flow in the presence or absence of sitagliptin. BNP caused dose‐dependent vasodilation; however, sitagliptin did not affect this response. GLP‐1 and BNP had no effect on net norepinephrine release.ConclusionsThese data suggest that GLP‐1 does not act as a direct vasodilator in humans and does not contribute to sympathetic activation. Sitagliptin does not regulate vascular function in healthy humans by affecting the degradation of GLP‐1 and BNP.Clinical Trial RegistrationURL: www.clinicaltrials.gov/ Unique identifier: NCT01413542.

Sitagliptin Use in Patients With Diabetes and Heart Failure: A Population-Based Retrospective Cohort Study

ObjectivesThe study objective was to evaluate the effects of sitagliptin in patients with type 2 diabetes (T2D) and heart failure (HF). BackgroundThere is uncertainty in the literature about whether dipeptidyl peptidase (DPP)-4 inhibitors cause harm in patients with HF and T2D. MethodsWe analyzed data from a national commercially insured U.S. claims database. Patients with incident HF were identified from individuals with T2D initially treated with metformin or sulfonylurea and followed over time. Subjects subsequently using sitagliptin were compared with those not using sitagliptin in the 90 days before our primary outcome of all-cause hospital admission or death using a nested case-control analysis after adjustment for demographics and clinical and laboratory data. HF-specific hospital admission or death also was assessed. ResultsA total of 7,620 patients with diabetes and incident HF met our inclusion criteria. Mean (SD) age was 54 years (9), and 58% (3,180) were male. Overall, 887 patients (12%) were exposed to sitagliptin therapy (521 patient years of exposure) after incident HF. Our primary composite endpoint occurred in 4,137 patients (54%). After adjustment, sitagliptin users were not at an increased risk for the primary endpoint (7.1% vs. 9.2%, adjusted odds ratio [aOR]: 0.84, 95% confidence interval [CI]: 0.69 to 1.03) or each component (hospital admission 7.5% vs. 9.2%, aOR: 0.93, 95% CI: 0.76 to 1.14; death 6.9% vs. 9.3%, aOR: 1.16, 95% CI: 0.68 to 1.97). However, sitagliptin use was associated with an increased risk of HF hospitalizations (12.5% vs. 9.0%, aOR: 1.84, 95% CI: 1.16 to 2.92). ConclusionsSitagliptin use was not associated with an increased risk of all-cause hospitalizations or death, but was associated with an increased risk of HF-related hospitalizations among patients with T2D with pre-existing HF.

Di-peptidyl peptidase-4 inhibitor sitagliptin protects vascular function in metabolic syndrome: possible role of epigenetic regulation.

Metabolic syndrome (MetS) is a complex medical disorder characterized by insulin resistance, hypertension, and high risk of coronary disease and stroke. Microvascular rarefaction and endothelial dysfunction have also been linked with MetS, and recent evidence from clinical studies supports the efficacy of incretin-based antidiabetic therapies for vascular protection in diabetes. Previous studies pointed out the importance of dipeptidyl peptidase-4 (DPP-4) inhibition in endothelial cells due to getting protection against metabolic pathologies. We therefore aimed to investigate the acute effects of a DPP-4 inhibitor, sitagliptin, on vascular function in rats with high-sucrose diet-induced MetS. In order to elucidate the mechanisms implicated in the effects of DPP-4 inhibition, we tested the involvement of NO pathway and epigenetic regulation in the MetS. Acute use of sitagliptin protects the vascular function in the rats with MetS in part due to NO pathway via restoring the depressed aortic relaxation responses mediated by receptors. Application of sitagliptin enhanced the depressed phosphorylation levels of both the endothelial NO synthase and the apoptotic status of protein kinase B, known as Akt, in endothelium-intact thoracic aorta from rats with MetS. One-hour application of sitagliptin on aortic rings from rats with MetS also induced remarkable histon posttranslational modifications such as increased expression of H3K27Me3, but not of H3K27Me2, resulting in an accumulation of the H3K27Me3. Our findings suggest that, in addition to its well-known hypoglycemic action, sitagliptin may also have beneficial effects on hyperglycemia-induced vascular changes in an endotheium-dependent manner. These present results with sitagliptin aside from the glycaemic control, may demonstrate its important role in the treatment of patients with MetS.

Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: systematic review and meta-analysis of randomised and non-randomised studies

Objective To investigate the risk of pancreatitis associated with the use of incretin-based treatments in patients with type 2 diabetes mellitus.Design Systematic review and meta-analysis.Data sources Medline, Embase, the Cochrane...

Preliminary Study Characterizing the Use of Sitagliptin for Glycemic Control in Healthy Beagle Dogs with Normal Gluco-Homeostasis

ABSTRACTSitagliptin is a dipeptidyl peptidase-4 inhibitor aimed at treating Type 2 diabetes mellitus (T2DM) and T1DM, by increasing blood levels of Glucagon-like peptide 1 (GLP-1) and insulin. The objective of this preliminary study is to characterize Sitagliptin’s ability for glycemic control, in healthy dogs under an oral glucose tolerance test (OGTT) environment. Overall, Sitagliptin did not result in any significant changes to temporal glucose and insulin concentrations. However, a ~55% increase in median total GLP-1 AUC0–120min was observed, as compared to baseline control in healthy dogs (n=5), thus indicating a similar mode of action of Sitagliptin between healthy dogs and humans. Future studies to validate the use of Sitagliptin with dogs suffering from insulin independent diabetes are warranted.

Sitagliptin induced acute severe nasopharyngitis

Acute nasopharyngitis is one of the distressing adverse effects seen with the use of dipeptidyl peptidase-4 inhibitors like sitagliptin. Here, we report a case of acute severe nasophryngitis with the use of sitagliptin for diabetes mellitus.

Significant Differences in Effects of Sitagliptin Treatment on Body Weight and Lipid Metabolism Between Obese and Non-Obese Patients With Type 2 Diabetes

Background: We previously reported that HbA1c levels and body weight significantly decreased by 0.6% and by 0.8 kg, respectively, at 6 months after sitagliptin treatment started. We found a significant and negative correlation between change in body weight and body mass index (BMI) at baseline. Methods: We retrospectively sub-analyzed effects of 6-month treatment with sitagliptin on glucose and lipid metabolism, blood pressure, body weight and renal function in patients with type 2 diabetes, by dividing 173 type 2 diabetic subjects into obese group (BMI is greater than or equal to 25) and non-obese group (BMI < 25). Results: At baseline, obese group was significantly younger than non-obese group. Diastolic blood pressure, low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG), and estimated glomerular filtration rate (eGFR) in obese group were significantly higher than in non-obese group. Serum high-density lipoprotein-cholesterol (HDL-C) in obese group was significantly lower than in non-obese group. At 6 months after the start of sitagliptin use, body weight significantly decreased in obese group, while body weight did not change in non-obese group. HbA1c significantly decreased in both groups. Serum HDL-C significantly decreased in obese group, while serum HDL-C did not change in non-obese group. Serum TG significantly decreased in obese group, while serum TG significantly increased in non-obese group. Change in serum TG was significantly and inversely correlated with BMI at baseline. Conclusions: We found significant differences in effects of sitagliptin treatment on body weight and lipid metabolism between obese and non-obese patients with type 2 diabetes. Sitagliptin improved HbA1c regardless of the existence of obesity. In obese people, sitagliptin significantly reduced body weight and serum TG. Sitagliptin reduced serum TG in a baseline-BMI-dependent manner. J Endocrinol Metab. 2014;4(5-6):136-142 doi: http://dx.doi.org/10.14740/jem243w

Significant Differences in Effects of Sitagliptin Treatment on Body Weight and Lipid Metabolism Between Obese and Non-Obese Patients With Type 2 Diabetes

Background: We previously reported that HbA1c levels and body weight significantly decreased by 0.6% and by 0.8 kg, respectively, at 6 months after sitagliptin treatment started. We found a significant and negative correlation between change in body weight and body mass index (BMI) at baseline. Methods: We retrospectively sub-analyzed effects of 6-month treatment with sitagliptin on glucose and lipid metabolism, blood pressure, body weight and renal function in patients with type 2 diabetes, by dividing 173 type 2 diabetic subjects into obese group (BMI is greater than or equal to 25) and non-obese group (BMI &lt; 25). Results: At baseline, obese group was significantly younger than non-obese group. Diastolic blood pressure, low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG), and estimated glomerular filtration rate (eGFR) in obese group were significantly higher than in non-obese group. Serum high-density lipoprotein-cholesterol (HDL-C) in obese group was significantly lower than in non-obese group. At 6 months after the start of sitagliptin use, body weight significantly decreased in obese group, while body weight did not change in non-obese group. HbA1c significantly decreased in both groups. Serum HDL-C significantly decreased in obese group, while serum HDL-C did not change in non-obese group. Serum TG significantly decreased in obese group, while serum TG significantly increased in non-obese group. Change in serum TG was significantly and inversely correlated with BMI at baseline. Conclusions: We found significant differences in effects of sitagliptin treatment on body weight and lipid metabolism between obese and non-obese patients with type 2 diabetes. Sitagliptin improved HbA1c regardless of the existence of obesity. In obese people, sitagliptin significantly reduced body weight and serum TG. Sitagliptin reduced serum TG in a baseline-BMI-dependent manner. J Endocrinol Metab. 2014;4(5-6):136-142 doi: http://dx.doi.org/10.14740/jem243w

Efficacy and safety of sitagliptin for the treatment of new-onset diabetes after renal transplantation.

New-onset diabetes after transplantation (NODAT) is a common comorbidity after renal transplantation. Though metformin is the first-line agent for the treatment of type 2 diabetes, in renal transplant recipients, metformin is frequently avoided due to concerns about renal dysfunction and risk for lactic acidosis. Therefore, alternative first-line agents for the treatment of NODAT in renal transplant recipients are needed. Sitagliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, has a low incidence of hypoglycemia, is weight neutral, and, in a small study, did not affect immunosuppressant levels. However, long-term sitagliptin use for the treatment of NODAT in kidney transplant recipients has not been studied. We retrospectively analyzed renal transplant recipients diagnosed with NODAT and treated with sitagliptin to assess safety and efficacy. Twenty-two patients were started on sitagliptin alone. After 12 months of followup, 19/22 patients remained on sitagliptin alone with a significant improvement in hemoglobin A1c. Renal function and immunosuppressant levels remained stable. Analysis of long-term followup (32.5 ± 17.8 months) revealed that 17/22 patients remained on sitagliptin (mean hemoglobin A1c < 7%) with 9/17 patients remaining on sitagliptin alone. Transplant-specific adverse events were rare. Sitagliptin appears safe and efficacious for the treatment of NODAT in kidney transplant recipients.

Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study

Sitagliptin, a dipeptidyl-peptidase 4 (DPP-4) inhibitor, improves blood glucose control in patients with type 2 diabetes by blocking cleavage of glucagon-like peptide 1 (GLP-1). In type 2 diabetes patients sitagliptin use is associated with an increase in minor infections, and in new-onset type 1 diabetes patients the ability of sitagliptin to dampen autoimmunity is currently being tested. DPP-4, also known as CD26, is expressed on leucocytes and can inactivate many chemokines important for leucocyte migration, as well as act as a co-stimulatory molecule on T cells. Therefore, this study was conducted to test whether sitagliptin is immunomodulatory. In this randomized, placebo-controlled trial, healthy volunteers were given sitagliptin or placebo daily for 28 days, and blood was drawn for immune assays. No significant differences were observed in the percentage of leucocyte subsets within peripheral blood mononuclear cells (PBMCs), plasma chemokine/cytokine levels or cytokines released by stimulation of PBMCs with either lipopolysaccharide (LPS) or anti-CD3. Individuals taking sitagliptin displayed increases in the percentage of cells expressing higher levels of CD26 at early time-points compared to placebo controls, but these differences resolved by day 28 of treatment. Therefore, in healthy volunteers, treatment with sitagliptin daily for 28 days does not overtly alter systemic immune function.

A review of sitagliptin with special emphasis on its use in moderate to severe renal impairment.

Sitagliptin is the first dipeptidylpeptidase-4 inhibitor to be used in the management of type 2 diabetes. It is widely used as an add-on therapy to ongoing management or as monotherapy where it is deemed necessary. It has been found to be beneficial in improving β-cell function and glycemic control, and also is used in special circumstances like chronic kidney disease, with appropriate dose reductions. Overall, cardiovascular outcomes are no different from other oral hypoglycemic agents. In this review article we have summarized all the previous studies relevant to sitagliptin use in clinical practice and emphasized its use in various stages of chronic kidney disease.

The faces of pharmacy: Students and pharmacists stepping forward

The faces of pharmacy: Students and pharmacists stepping forward

Comparative safety and effectiveness of sitagliptin in patients with type 2 diabetes: retrospective population based cohort study

Objective To determine if the use of sitagliptin in newly treated patients with type 2 diabetes is associated with any changes in clinical outcomes.Design Retrospective population based cohort study.Setting Large...

A New Preventive Strategy for Hypoglycemia Incorporating Added Food Diet in Patients with Type 2 Diabetes Who Received Sitagliptin Therapy

There has been concern as to whether dipeptidyl peptidase-4 (DPP-4) inhibitors can be used safely in patients with relatively good glycemic control. This study, approved by the institutional review board of Hanzoumon Diabetes City Atlas Clinic, examined whether DPP-4 inhibitor sitagliptin could safely achieve good glycemic control without severe hypoglycemia by employing the “added food” concept. The subjects were 60 patients (46 men and 14 women) with type 2 diabetes who started sitagliptin therapy during a 1-month period from December 15, 2009 to January 15, 2010. They were recommended to have added food between meals to prevent hypoglycemia, while maintaining the same daily calorie intake. HbA1c decreased from 7.1 ± 1.2% to 6.5 ± 0.6% after 6 months of sitagliptin treatment (p < 0.001). In patients with a baseline HbA1c <7%, it decreased from 6.5 ± 0.3% to 6.1 ± 0.4% (p < 0.001). Systolic blood pressure was significantly reduced from 127.7 ± 17.0 to 122.7 ± 17.9 mmHg in the patients with a baseline HbA1c < 7% (p = 0.018). However, body weight increased by approximately 900 g and high-density lipoprotein cholesterol decreased significantly from 1.57 ± 0.46 to 1.43 ± 0.35 mmol/L (p < 0.01) in the patients concomitantly receiving sulfonylureas with sitagliptin. Excellent glycemic control was achieved by sitagliptin treatment together with the added food concept. However, combined use of sitagliptin with sulfonylureas requires attention to weight gain and the lipid profile. Further clinical studies will elucidate whether sitagliptin can decrease cardiovascular events as well as normalizing blood glucose and lowering the blood pressure.

AKI With Use of Sitagliptin – Do We Need to be Concerned?

AKI With Use of Sitagliptin – Do We Need to be Concerned?

Exenatide and sitagliptin are not associated with increased risk of acute renal failure: a retrospective claims analysis

This study evaluated whether the risk of acute renal failure (ARF) increases with exenatide and sitagliptin use. A retrospective cohort study of a large medical and pharmacy claims database was performed. Data for 4 91 539 patients were analysed. Cox proportional hazard models were used to compare the risk of ARF between diabetic and non-diabetic subjects and between diabetic patients treated with exenatide, sitagliptin and control medications. Adjusted Cox analyses showed diabetic subjects had a higher risk of ARF [HR 1.51, confidence interval (CI) 1.26-1.81, p < 0.001] than non-diabetic controls. Compared with diabetic controls, neither exenatide (HR 0.77, CI 0.42-1.41, p = 0.40) nor sitagliptin (HR 1.17, CI 0.82-1.65, p = 0.39) increased the risk of ARF. Our study revealed an increased incidence of ARF in diabetic versus non-diabetic patients but no association between use of exenatide or sitagliptin and ARF. Because of the limitations of this observational analysis, we cannot exclude the possibility of a very small increased risk.

Sitagliptin increases tau phosphorylation in the hippocampus of rats with type 2 diabetes and in primary neuron cultures

Increasing evidence supports an association between Alzheimer's disease (AD) and diabetes. In this context, anti-diabetic agents such as rosiglitazone and glucagon-like peptide (GLP)-1 have been reported to reduce pathologies associated with AD, including tau hyperphosphorylation, suggesting that such agents might be used to treat AD. One such anti-diabetic agent is sitagliptin, which acts through inhibition of dipeptidyl peptidase (DPP)-IV to increase GLP-1 levels. Given this action, sitagliptin would be predicted to reduce AD pathology. Accordingly, we investigated whether sitagliptin is effective in attenuating AD pathologies, focusing on tau phosphorylation in the OLETF type 2 diabetic rat model. Unexpectedly, we found that sitagliptin was not effective against pathological tau phosphorylation in the hippocampus of OLETF type 2 diabetes rats, and instead aggravated it. This paradoxically increased tau phosphorylation was attributed to activation of the tau kinase, GSK3β (glycogen synthase kinase 3β). Sitagliptin also increased ser-616 phosphorylation of the insulin receptor substrate (IRS)-1, suggesting increased insulin resistance in the brain. These phenomena were recapitulated in primary rat cortical neurons treated with sitagliptin, further confirming sitagliptin's effects on AD-related pathologies in neurons. These results highlight the need for caution in considering the use of sitagliptin in AD therapy.

Diabetes mellitus in the young: Gliptins or sulfonylurea after metformin?

Introduction:Diagnosis and initial management of diabetes mellitus (DM) in the young are clinical dilemma. Gliptins may be a safer and more effective option than sulfonylureas. Few Indian studies have addressed this issue of clinical relevance.Aim:To compare the use of sitagliptin and glimepiride as early add-on drugs along with metformin in young patients with DM to achieve optimum glycemic targets.Methods:This was a prospective, open-label, cohort study set in a tertiary care hospital in North India. Newly diagnosed patients of DM ≤35 year of age were initially treated to pre-defined glycemic goals (Fasting plasma glucose (FPG) 70-130, post prandial glucose (PPG) < 180 mg/dl) with insulin and metformin 1 g for 8 weeks. Insulin was discontinued and metformin increased to 2 g daily for next 4 weeks. Thereafter, glimepiride 1 mg or sitagliptin 100 mg was randomly added to those who were not maintaining the set glucose targets. Dose of glimepiride was uptitrated every 4 weeks upto a maximum of 4 mg. Three groups (Gp A: Metfromin 2 g/d, Gp B: Metformin 2 g + Glimepiride 1-4 mg/d, and Gp C: Metformin 2 g + sitagliptin 100 mg/d) were followed up over next 24 weeks. They were compared for glycemic control and weight change. Those failing therapy on these drugs (FPG > 180, PPG > 250 mg/dl with/without catabolic symptoms/ketosis) were withdrawn.Results:Sitagliptin with metfromin and metfromin alone group fared better than the glimepiride group for glycemic control, lesser treatment failures, and less weight gain.Conclusion:In this limited study, we found that sitagliptin is a safer and more effective option in young, newly diagnosed patients with DM. Findings of this study are relevant for clinical practice in Indian setting.