No abstract available.
Diabetes Mellitus, Type 2 ; Pyrazines ; Triazoles ; Sitagliptin Phosphate

No abstract available.
Diabetes Mellitus, Type 2 ; Pyrazines ; Triazoles ; Sitagliptin Phosphate

BACKGROUND: To evaluate the clinical efficacy of sitagliptin for reducing plasma glucose levels in Korean subjects with type 2 diabetes mellitus during a 14-week treatment period. METHODS: Our study design involved the addition of 100 mg sitagliptin once-daily to three ongoing combination therapy regimens and changing from glimepiride and metformin to sitagliptin and metformin. RESULTS: The addition of sitagliptin 100 mg/day produced a statistically significant reduction in mean HbA1c level (mean HbA1c reduction of 0.99+/-0.85%, P<0.01). In the group taking a combination of sitagliptin and metformin (n=143, initial mean HbA1c level=7.48%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 0.72+/-0.76% (P<0.01), 47+/-65 mg/dL (P<0.01), and 15+/-44 mg/dL (P<0.01), respectively. In the group taking a combination of sitagliptin, glimepiride, and metformin (n=125, initial mean HbA1c level=8.42%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 1.09+/-0.86% (P<0.01), 62+/-64 mg/dL (P<0.01), and 31+/-45 mg/dL (P<0.01), respectively. In the group taking a combination of sitagliptin, glimepiride, metformin, and alpha-glucosidase inhibitor (n=63, initial mean HbA1c level=9.19%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 1.27+/-0.70% (P<0.01), 72+/-65 mg/dL (P<0.01), and 35+/-51 mg/dL (P<0.01), respectively. In the group that had previous hypoglycemic events and that changed from glimepiride to sitagliptin, HbA1c level did not change but fasting glucose increased significantly (14+/-29 mg/dL, P<0.01). CONCLUSION: Sitagliptin combination therapy for 14 weeks significantly improved glycemic control and was well-tolerated in Korean subjects with type 2 diabetes mellitus.
alpha-Glucosidases ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Metformin ; Plasma ; Pyrazines ; Sulfonylurea Compounds ; Triazoles ; Sitagliptin Phosphate

BACKGROUND: Sitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects. METHODS: We obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (DeltaHbA1c) and fasting plasma glucose (DeltaFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in DeltaHbA1c or >20% in DeltaFPG levels at 24 weeks. RESULTS: We classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70+/-2.40 vs. 26.00+/-2.26, P< or =0.01) and were younger (58.83+/-11.57 years vs. 62.87+/-12.09 years, P=0.03) than the non-responder group. CONCLUSION: In Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders.
Body Mass Index ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Insulin ; Metformin ; Plasma ; Pyrazines ; Triazoles ; Sitagliptin Phosphate

BACKGROUND/AIMS: The gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the 13C-acetic acid breath test. METHODS: Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted for overnight and were randomly assigned to receive 50 mg sitagliptin 2 hours before ingestion of the liquid test meal (200 kcal per 200 mL, containing 100 mg 13C-acetate) or the test meal alone. Under both conditions, breath samples were collected for 150 minutes following the meal. Liquid gastric emptying was estimated by the values of the following parameters: the time required for 50% emptying of the labeled meal (T1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (Tlag), the gastric emptying coefficient and the regression-estimated constants (beta and kappa), calculated by using the 13CO2 breath excretion curve using the conventional formulae. The parameters between the 2 test conditions were compared statistically. RESULTS: No significant differences in the calculated parameters, including T1/2, Tlag, gastric emptying coefficient or beta and kappa, were observed between the 2 test conditions. CONCLUSIONS: The present study revealed that single-dose sitagliptin intake had no significant influence on the rate of liquid gastric emptying in asymptomatic volunteers.
Breath Tests ; Cross-Over Studies ; Eating ; Gastric Emptying ; Gastrointestinal Motility ; Humans ; Incretins ; Male ; Meals ; Pyrazines ; Triazoles ; Sitagliptin Phosphate

BACKGROUND: To investigate the clinical results of sitagliptin (SITA) and the characteristics of the treatment failure group or of low responders to SITA. METHODS: A retrospective study of type 2 diabetic patients reviewed 99 cases, including 12 treatment failure cases, who stopped SITA because of worsening patients' condition, and 87 cases, who continued treatment over five visits (total 9.9+/-10.1 months) after receiving the prescription of SITA from December 2008 to June 2009. Subjects were classified as five groups administered SITA as an initial combination with metformin (MET), add-on to metformin or sulfonylurea, and switching from sulfonylurea or thiazolidinedione. The changes in HbA1c level from the first to last visit (DeltaHbA1c) in treatment maintenance group were subanalyzed. RESULTS: The HbA1c level was significantly reduced in four groups, including initial coadministration of SITA with metformin (DeltaHbA1c=-1.1%, P<0.001), add-on to MET (DeltaHbA1c=-0.6%, P=0.017), add-on to sulfonylurea (DeltaHbA1c=-0.5%, P<0.001), and switching from thiazolidinedione (DeltaHbA1c=-0.3%, P=0.013). SITA was noninferior to sulfonlyurea (DeltaHbA1c=-0.2%, P=0.63). There was no significant adverse effect. The treatment failure group had a longer diabeties duration (P=0.008), higher HbA1c (P=0.001) and fasting plasma glucose (P=0.003) compared to the maintenance group. Subanalysis on the tertiles of DeltaHbA1c showed that low-response to SITA (tertile 1) was associated with a longer diabetes duration (P=0.009) and lower HbA1c (P<0.001). CONCLUSION: SITA was effective and safe for use in Korean type 2 diabetic patients. However, its clinical responses and long-term benefit-harm profile is yet to be established.
Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Humans ; Metformin ; Plasma ; Prescriptions ; Pyrazines ; Retrospective Studies ; Thiazolidinediones ; Treatment Failure ; Treatment Outcome ; Triazoles ; Sitagliptin Phosphate

New therapeutics for type 2 diabetes using incretin hormone were introduced recently. Incretin-based therapies consist of two types: GLP-1 agonists mainly acting on the GLP-1 receptor and dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors). The former is resistant to DPP-4 and injectable. The latter is oral medications raising endogenous GLP-1 by inhibiting the degrading enzyme DPP-4. The incretin based therapies are promising and more commonly used due to their action and safety profile. Stimulation of insulin secretion by these drugs occurs in a glucose-dependent manner. Incretin based therapies have low risk for hypoglycemia. The subsequent review outlines evidence from selected clinical trials of the currently available GLP-1 agonists, exenatide and liraglutide, and DPP-4 inhibitors, sitagliptin and vildagliptin.
Adamantane ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptide 1 ; Hypoglycemia ; Incretins ; Insulin ; Nitriles ; Peptides ; Pyrazines ; Pyrrolidines ; Receptors, Glucagon ; Triazoles ; Venoms ; Glucagon-Like Peptide-1 Receptor ; Liraglutide ; Sitagliptin Phosphate

While there are many therapies for type 2 diabetes are available including insulin secretagogues, insulin sensitizers and exogenous insulin, many patients are unable to reach recommended therapeutic targets. Incretin-based therapies have recently been introduced into clinical practice, and these novel therapies may make it possible to achieve improved glycemic control either with no weight gain (dipeptidyl peptidase-4 [DPP-4] inhibitors sitagliptin and vildagliptin, or with weight loss (glucagon-like peptide-1 [GLP-1] mimetics exenatide and liraglutide). This article aims to provide an overview of efficacy and safety data regarding incretinbased clinical trials in type 2 diabetic patients, and propose a systematic approach to treatment including patient selection and optimal treatment combination. In addition, preclinical data suggest that incretin-based therapies may also preserve-cell function. Therefore, these agents hold out promise of a truly disease-modifying therapy that would target the progressive nature of type 2 diabetes. Additional clinical trials will be required to test such hypothesis.
Adamantane ; Diabetes Mellitus, Type 2 ; Humans ; Incretins ; Insulin ; Nitriles ; Patient Selection ; Peptides ; Pyrazines ; Pyrrolidines ; Sitagliptin Phosphate ; Triazoles ; Venoms ; Weight Gain ; Weight Loss

During past several years, a novel class of antihyperglycemic agents, dipeptidyl peptidase-4 (DPP-4) inhibitors, has become one of the most important options in the management of type 2 diabetes. These agents have unique insulinotropic actions as well as other advantages such as lower hypoglycemia and a weight-neutral effect compared to traditional insulin secretagogues. To date, 6 different DPP-4 inhibitors have been introduced: sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin and gemiglitin. This review provides a summary of the clinical data for each DPP-4 inhibitor, and discusses the similarities and differences between them.
Adamantane ; Diabetes Mellitus ; Dipeptides ; Dipeptidyl-Peptidase IV Inhibitors ; Hypoglycemia ; Hypoglycemic Agents ; Incretins ; Insulin ; Nitriles ; Piperidines ; Purines ; Pyrazines ; Pyrrolidines ; Quinazolines ; Triazoles ; Uracil ; Linagliptin ; Sitagliptin Phosphate

Boronic Acids ; Bortezomib ; Humans ; Liver Diseases ; Proteasome Inhibitors ; Pyrazines