Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Saxagliptin: A Selective DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus.

ABSTRACT: The prevalence of type 2 diabetes mellitus is high and growing rapidly. Suboptimal glycemic control provides opportunities for new treatment options to improve the morbidity and mortality of this progressive disease. Saxagliptin, a selective DPP-4 inhibitor, increases endogenous incretin levels and incretin acitivty. In controlled clinical trials saxagliptin reduces both fasting and postprandial glucose and works in monotherapy and in combination with metformin, TZDs and sulfonylureas. Saxagliptin has a very favourable side effect profile and may have other beneficial non-glycemic effects. The authors review the current available evidence for the safety, efficacy and saxagliptin's place in therapy for type 2 diabetes mellitus. As understanding of the incretin hormones (GLP-1, GIP) expand we may see additional important non-glycemic effects that may affect the chronic management of type 2 diabetes mellitus.

SUBMITTER: Shubrook J

PROVIDER: S-EPMC3411543 | biostudies-other | 2011

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Saxagliptin: A Selective DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus.

Shubrook Jay J Colucci Randall R Guo Aili A Schwartz Frank F

Clinical medicine insights. Endocrinology and diabetes 20110112

The prevalence of type 2 diabetes mellitus is high and growing rapidly. Suboptimal glycemic control provides opportunities for new treatment options to improve the morbidity and mortality of this progressive disease. Saxagliptin, a selective DPP-4 inhibitor, increases endogenous incretin levels and incretin acitivty. In controlled clinical trials saxagliptin reduces both fasting and postprandial glucose and works in monotherapy and in combination with metformin, TZDs and sulfonylureas. Saxaglipt ...[more]

PMID: 22879789

Similar Datasets

Saxagliptin for the treatment of type 2 diabetes mellitus: assessing cardiovascular data.

Project description:Patients with type 2 diabetes mellitus (T2DM) are at high risk for cardiovascular (CV) disease; however, conclusive evidence that glycemic control leads to improved cardiovascular outcomes is lacking. Saxagliptin is a potent, selective dipeptidyl peptidase-4 inhibitor approved as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. Saxagliptin was evaluated in a series of phase III trials as monotherapy; add-on therapy to metformin, a sulfonylurea, or a thiazolidinedione; and as initial therapy in combination with metformin. Saxagliptin consistently improved glycemic control (as reflected by significant decreases in glycated hemoglobin, fasting plasma glucose, and postprandial glucose compared with controls) and was generally well tolerated. In these analyses, saxagliptin had clinically neutral effects on body weight, blood pressure, lipid levels, and other markers of CV risk compared with controls. A retrospective meta-analysis of 8 phase II and phase III trials found no evidence that saxagliptin increases CV risk in patients with T2DM (Cox proportional hazard ratio, 0.43; 95% CI, 0.23-0.80 for major adverse cardiovascular events retrospectively adjudicated). Instead, it raised the hypothesis that saxagliptin may reduce the risk of major adverse CV events. A long-term CV outcome trial, Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-THrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) is currently ongoing to determine whether saxagliptin reduces CV risk in T2DM.

| S-EPMC3277488 | biostudies-literature

Discovery of Imigliptin, a Novel Selective DPP-4 Inhibitor for the Treatment of Type 2 Diabetes.

Project description:We report our discovery of a novel series of potent and selective dipeptidyl peptidase IV (DPP-4) inhibitors. Starting from a lead identified by scaffold-hopping approach, our discovery and development efforts were focused on exploring structure-activity relationships, optimizing pharmacokinetic profile, improving in vitro and in vivo efficacy, and evaluating safety profile. The selected candidate, Imigliptin, is now undergoing clinical trial.

| S-EPMC4137375 | biostudies-literature

Saxagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus.

Project description:The worldwide prevalence of type 2 diabetes mellitus (T2DM) is high, and the chronically poor metabolic control that can result from T2DM is associated with a high risk for microvascular and macrovascular complications. Because of the progressive pathophysiology of T2DM, oral antidiabetic agents often fail to provide sustained glycemic control, indicating the need for new therapies. Saxagliptin (Onglyza™; Bristol-Myers Squibb Company, Princeton, NJ, USA; AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA) is an oral dipeptidyl peptidase-4 inhibitor, recently approved for the treatment of T2DM.Saxagliptin significantly improves glycemic control vs placebo, as demonstrated by decreasing glycated hemoglobin, fasting plasma glucose, and postprandial plasma glucose levels when used as monotherapy; in initial combination with metformin; and as add-on therapy with metformin, sulfonylurea (SU), or thiazolidinedione (TZD). Saxagliptin also significantly improves ?-cell function, is weight neutral, has a low risk for hypoglycemia, and has been shown to have cardiovascular safety.The clinical profile for saxagliptin indicates that it is useful as an adjunct to diet and exercise as first-line monotherapy and in combination with metformin; or as add-on treatment for patients who cannot achieve glycemic control with a combination of diet and lifestyle changes and metformin, SU, or TZD.

| S-EPMC2963920 | biostudies-other

The efficacy and safety of the dipeptidyl peptidase-4 inhibitor saxagliptin in treatment-naive patients with type 2 diabetes mellitus: a randomized controlled trial.

Project description:UnlabelledBackgroundThe aim of this study was to assess efficacy and safety of saxagliptin monotherapy for up to 76 weeks in patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control, with main efficacy assessment at 24 weeks.Methods365 treatment-naïve patients with T2DM (HbA1c 7.0%-10.0%) were treated with saxagliptin 2.5 mg q.A.M., saxagliptin 2.5 mg q.A.M. with possible titration to saxagliptin 5 mg, saxagliptin 5 mg q.A.M., saxagliptin 5 mg q.P.M., or placebo. After week 24, patients in all groups were eligible for titration to saxagliptin 10 mg based on HbA1c ≥7%, and all unrescued placebo patients began blinded metformin 500 mg/day. Rescue with open-label metformin was available for patients with inadequate glycemic control.ResultsAt week 24, placebo-subtracted mean HbA1c reduction from baseline (LOCF) was significantly greater in the saxagliptin treatment groups vs placebo, and remained greater through week 76. Serious adverse events (AEs) and discontinuations due to AEs were similar in saxagliptin and control groups; incidence of confirmed hypoglycemia was low across all treatment groups (saxagliptin-treated, 2 [0.7]; control, 1 [1.4]).ConclusionsIn treatment-naïve patients with T2DM, saxagliptin monotherapy demonstrated statistically significant improvement in HbA1c compared with placebo at 24 weeks and was generally well tolerated for up to 76 weeks.Trial registrationClinicalTrials.gov Identifier: NCT00316082.

| S-EPMC3541110 | biostudies-literature

Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus.

Project description:Fatty acid binding protein 4 (FABP4), also known as adipocyte FABP or aP2, is secreted from adipocytes in association with lipolysis as a novel adipokine, and elevated serum FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the modulation of serum FABP4 level by therapeutic drugs. Sitagliptin (50 mg/day), a dipeptidyl peptidase 4 (DPP-4) inhibitor that increases glucagon-like peptide 1 (GLP-1), was administered to patients with type 2 diabetes (n = 24) for 12 weeks. Treatment with sitagliptin decreased serum FABP4 concentration by 19.7% (17.8 ± 1.8 vs. 14.3 ± 1.5 ng/ml, P < 0.001) and hemoglobin A1c without significant changes in adiposity or lipid variables. In 3T3-L1 adipocytes, sitagliptin or exendin-4, a GLP-1 receptor agonist, had no effect on short-term (2 h) secretion of FABP4. However, gene expression and long-term (24 h) secretion of FABP4 were significantly reduced by sitagliptin, which was not mimicked by exendin-4. Treatment with recombinant DPP-4 increased gene expression and long-term secretion of FABP4, and the effects were cancelled by sitagliptin. Furthermore, knockdown of DPP-4 in 3T3-L1 adipocytes decreased gene expression and long-term secretion of FABP4. In conclusion, sitagliptin decreases serum FABP4 level, at least in part, via reduction in the expression and consecutive secretion of FABP4 in adipocytes by direct inhibition of DPP-4.

| S-EPMC4655983 | biostudies-literature

Saxagliptin for type 2 diabetes.

Project description:Saxagliptin (Onglyza™) is a potent, selective, once-daily dipeptidyl peptidase-4 (DPP-4) inhibitor indicated for improving glycemic control in patients with type 2 diabetes (T2D). By blocking DPP-4, saxagliptin increases and prolongs the effects of incretins, a group of peptide hormones released by intestinal cells after meals, which stimulate glucose-dependent insulin secretion to lower blood glucose. In controlled clinical trials, saxagliptin administered as monotherapy or in combination with metformin, glyburide, or a thiazolidinedione improved glycemic control in a clinically significant manner, reflected by significant decreases in glycated hemoglobin (monotherapy, -0.5%; add-on to metformin, thiazolidinedione, or sulfonylurea, -0.6% to 0.9%; initial combination with metformin, -2.5%), fasting plasma glucose, and postprandial glucose compared with controls. Additionally, saxagliptin improved ?-cell function, reflected as increases in homeostasis model assessment (HOMA)-2?. Saxagliptin was generally well tolerated; it did not increase hypoglycemia compared with controls, and was weight neutral. A meta-analysis of Phase II and III trials showed that saxagliptin did not increase the risk of major cardiovascular events. Professional organizations have updated their guidelines for T2D to include a DPP-4 inhibitor as an early treatment option-either as initial therapy in combination with metformin, or as add-on therapy for patients whose glycemia is inadequately controlled by a single oral antidiabetic drug.

| S-EPMC3047974 | biostudies-other

Discovery of Novel Tricyclic Heterocycles as Potent and Selective DPP-4 Inhibitors for the Treatment of Type 2 Diabetes.

Project description:In our efforts to develop second generation DPP-4 inhibitors, we endeavored to identify distinct structures with long-acting (once weekly) potential. Taking advantage of X-ray cocrystal structures of sitagliptin and other DPP-4 inhibitors, such as alogliptin and linagliptin bound to DPP-4, and aided by molecular modeling, we designed several series of heterocyclic compounds as initial targets. During their synthesis, an unexpected chemical transformation provided a novel tricyclic scaffold that was beyond our original design. Capitalizing on this serendipitous discovery, we have elaborated this scaffold into a very potent and selective DPP-4 inhibitor lead series, as highlighted by compound 17c.

| S-EPMC4867478 | biostudies-literature

Determinants of saxagliptin use among patients with type 2 diabetes mellitus treated with oral anti-diabetic drugs.

Project description:BackgroundThe patterns and determinants of saxagliptin use among patients with type 2 diabetes mellitus (T2DM) are unknown in real-world settings. We compared the characteristics of T2DM patients who were new initiators of saxagliptin to those who were new initiators of non-dipeptidyl peptidase-4 (DPP-4) inhibitor oral anti-diabetic drugs (OADs) and identified factors associated with saxagliptin use.MethodsWe conducted a cross-sectional study within the Clinical Practice Research Datalink (CPRD), The Health Improvement Network (THIN), US Medicare, and the HealthCore Integrated Research Database (HIRD(SM)) across the first 36 months of saxagliptin availability (29 months for US Medicare). Patients were included if they were: 1) ≥18 years old, 2) newly prescribed saxagliptin or a non-DPP-4 inhibitor OAD, and 3) enrolled in their respective database for 180 days. For each saxagliptin initiator, we randomly selected up to ten non-DPP-4 inhibitor OAD initiators matched on age, sex, and geographic region. Conditional logistic regression was used to identify determinants of saxagliptin use.ResultsWe identified 64,079 saxagliptin initiators (CPRD: 1,962; THIN: 2,084; US Medicare: 51,976; HIRD(SM): 8,057) and 610,660 non-DPP-4 inhibitor OAD initiators (CPRD: 19,484; THIN: 19,936; US Medicare: 493,432; HIRD(SM): 77,808). Across all four data sources, prior OAD use, hypertension, and hyperlipidemia were associated with saxagliptin use. Saxagliptin initiation was also associated with hemoglobin A1c results >8% within the UK data sources, and a greater number of hemoglobin A1c measurements in the US data sources.ConclusionsIn these UK and US data sources, initiation of saxagliptin was associated with prior poor glycemic control, prior OAD use, and diagnoses of hypertension and hyperlipidemia.Trial registrationClinicalTrials.gov identifiers NCT01086280 , NCT01086293 , NCT01086319 , NCT01086306 , and NCT01377935.

| S-EPMC4404079 | biostudies-literature

The dipeptidyl peptidase (DPP)-4 inhibitors for type 2 diabetes mellitus in challenging patient groups.

Project description:Treating hyperglycemia is a critical aspect of managing type 2 diabetes mellitus (T2DM), but can be especially challenging in patients from vulnerable groups such as those with chronic kidney disease, African Americans, and older people. The dipeptidyl peptidase (DPP)-4 inhibitors are relatively new oral antidiabetes drugs that have been incorporated into treatment algorithms over the past few years and have also been studied in these vulnerable patients. Clinical trials with DPP-4 inhibitors have now been reported for all these patient groups and have demonstrated significant improvements in measures of hyperglycemia, with a good safety profile. Based on the current evidence, it appears that the DPP-4 inhibitors are worthy of consideration not only for the most straightforward patients with T2DM, but also for these vulnerable patients.

| S-EPMC3898344 | biostudies-literature

The cost-effectiveness of dapagliflozin compared to DPP-4 inhibitors in the treatment of type 2 diabetes mellitus in the Netherlands.

Project description:AimWhen glycaemic control for people with type 2 diabetes is not achieved with metformin and sulfonylurea alone, adding another oral anti-diabetes drug, such as a sodium-glucose co-transporter 2 (SGLT2) or dipeptidyl peptidase-4 (DPP-4) inhibitor, is an alternative to starting insulin. The aim of this study is to determine the cost-effectiveness of dapagliflozin (an SGLT2 inhibitor) compared with DPP-4 inhibitors when added to metformin and sulfonylurea in people with type 2 diabetes in the Netherlands.MethodsA cost-utility analysis is performed using the Cardiff diabetes model, a fixed-time increment stochastic simulation model informed by 'United Kingdom Prospective Diabetes Study 68' risk equations. The base-case analysis uses a 40-year time horizon, a Dutch societal perspective and differential discounting (4% for costs, 1.5% for effects). Inputs are obtained from the literature and Dutch price lists. Univariate and probabilistic sensitivity analysis are performed.ResultsDapagliflozin is dominant compared with DPP-4 inhibitors, resulting in a €990 cost saving and a 0.28 quality-adjusted life year gain over 40 years. Cost savings are associated mainly with treatment costs and a reduced incidence of micro- and macrovascular complications, among others nephropathy, myocardial infarction and stroke. Results are robust to changes in input parameters.ConclusionsDapagliflozin is a cost-saving alternative to DPP-4 inhibitors when added to metformin and sulfonylurea. The incidence of micro- and macrovascular complications is lower for people treated with dapagliflozin. Uncertainty around this outcome is low.

| S-EPMC8048925 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data