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CV181-040 Investigators. Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: A randomised controlled trial

Diabetes Center, Federal University of São Paulo, São Paulo, Brazil.
International Journal of Clinical Practice (Impact Factor: 2.54). 07/2009; 63(9):1395-406. DOI: 10.1111/j.1742-1241.2009.02143.x
Source: PubMed

ABSTRACT Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy.
A total of 768 patients (18-77 years; HbA(1c) screening >or= 7.5 to <or= 10.0%) were randomised and treated with saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg vs. glyburide 10 mg for 24 weeks. Blinded uptitration glyburide was allowed in the glyburide-only arm to a maximum total daily dose of 15 mg. Efficacy analyses were performed using ANCOVA and last-observation-carried-forward methodology.
At week 24, 92% of glyburide-only patients were uptitrated to a total glyburide dose of 15 mg/day. Saxagliptin 2.5 and 5 mg provided statistically significant adjusted mean decreases from baseline to week 24 vs. uptitrated glyburide, respectively, in HbA(1c) (-0.54%, -0.64% vs. +0.08%; both p < 0.0001) and fasting plasma glucose (-7, -10 vs. +1 mg/dl; p = 0.0218 and p = 0.002). The proportion of patients achieving an HbA(1c) < 7% was greater for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide (22.4% and 22.8% vs. 9.1%; both p < 0.0001). Postprandial glucose area under the curve was reduced for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide (-4296 and -5000 vs. +1196 mg.min/dl; both p < 0.0001). Adverse event occurrence was similar across all groups. Reported hypoglycaemic events were not statistically significantly different for saxagliptin 2.5 (13.3%) and 5 mg (14.6%) vs. uptitrated glyburide (10.1%).
Saxagliptin added to submaximal glyburide therapy led to statistically significant improvements vs. uptitration of glyburide alone across key glycaemic parameters and was generally well tolerated.

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    • "patients with type 2 diabetes mellitus who received saxagliptin. On the other hand, there are studies that showed a small increase in body weight after treatment with saxagliptin [118] [119]. "
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    ABSTRACT: Currently, obesity and its associated complications are considered major public health problems worldwide. Because the causes are multifactorial and complex, different treatment methods are used, which include diet and exercise, as well as the use of drugs, although they can have adverse side effects. A new target for the treatment of obesity may be the incretin system, which consists of hormones that seem to contribute to weight loss. In this sense, some studies have shown a relationship between weight loss and drugs related to incretin system, including glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. The objective of this review is to summarize the association between the incretin system and obesity treatment. Copyright © 2015. Published by Elsevier Inc.
    Metabolism 05/2015; DOI:10.1016/j.metabol.2015.05.012 · 3.61 Impact Factor
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    • "DPP-4 inhibitors demonstrate different target mechanisms than sulfonylureas, and combination treatment not only improves glycemic control but minimizes the weaknesses of each drug. Previous studies report the effects of combination treatment without significant increases in the risk of AEs such as hypoglycemia [32, 33]. A recent study reports the efficacy on glucose fluctuation when added to DPP-4 inhibitors and administered to patients receiving ongoing sulfonylurea-based therapy [34]. "
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    ABSTRACT: Purpose Gemigliptin is approved for the treatment of type II diabetes mellitus. Sulfonylureas are commonly used in combination with other antidiabetic drugs to improve glycemic control. The objective of this study was to evaluate the pharmacokinetics, safety, and tolerability of gemigliptin and glimepiride combination therapy compared with those of monotherapies. Methods A randomized, open-label, crossover study was performed on healthy Korean male volunteers. Each subject received the following treatments (A and B) with a 7-day washout period: treatment A consisted of gemigliptin 50 mg once daily administered orally for 6 days, followed by concomitant oral dosing of glimepiride 4 mg and gemigliptin 50 mg on day 7; treatment B consisted of a single dose of glimepiride 4 mg. Blood samples were collected up to 24-h postdose on day 6 (gemigliptin) and day 7 (gemigliptin and glimepiride) following treatment A, and on day 1 (glimepiride) following treatment B. Concentrations of gemigliptin, glimepiride, and metabolites were determined using validated liquid chromatography–tandem mass spectrometry (LC–MS/MS). Safety assessments were performed throughout the study. Results Twenty-three subjects completed the study. The geometric mean ratios (GMRs) of Cmax,ss and AUCτ,ss for gemigliptin were 1.0097 [90 % confidence interval (CI) 0.924–1.103] and 0.9997 (90 % CI 0.976–1.024), respectively. For glimepiride, the GMRs of Cmax and AUClast were 1.031 (90 % CI 0.908–1.172) and 0.995 (90 % CI 0.902–1.097), respectively. Both combination and monotherapy were well tolerated, and no serious adverse events were reported. Conclusion Gemigliptin and glimepiride did not alter the pharmacokinetic properties of each other when they were co-administered in healthy volunteers, and were generally tolerated.
    Drugs in R & D 06/2014; 14(3). DOI:10.1007/s40268-014-0054-8 · 1.71 Impact Factor
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    • "GLP-1 released after meals but degraded by dipeptidyl peptidase-4 (DPP-4) rapidly. The DPP-4 inhibitors block the rapid inactivation of GLP-1 and improve glycaemic control [13]. It has been indicated that dipeptidyl peptidase-4 inhibitors (DPP4i) are superior to traditional oral hypoglycemic agents in terms of the efficacy and tolerability [14-17]. "
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    ABSTRACT: Background The oral DPP-4 inhibitors are new incretin-based therapies for treatment of type 2 diabetes. To assess the efficacy and safety of three DPP-4 inhibitors (Saxagliptin, Sitagliptin and Vildagliptin) as add-on therapy to dual combination of traditional oral hypoglycemic agents in Chinese type 2 diabetes patients. Methods In this 24-week, randomized, open-label, parallel clinical trial, we enrolled inadequately controlled (glycosylated haemoglobin A1c [HbA1c] ≥7.5% to ≤10%) patients with type 2 diabetes, who were treated by dual combination of metformin and another traditional oral hypoglycemic agent (glimepiride, acarbose or pioglitazone). 207 patients had been randomized to add-on 5 mg saxagliptin group or 100 mg sitagliptin once daily group, or 50 mg vildagliptin twice daily group for 24 weeks. HbA1c, fasting and postprandial blood glucose (FBG and P2hBG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated. Result After 24 weeks, HbA1c, FBG, and P2hBG of each group were significantly decreased. (saxagliptin vs vildagliptin vs sitagliptin: HbA1c: -1.2% vs -1.3% vs -1.1%; FBG: -1.8 mmol/l vs -2.4 mmol/l vs -1.5 mmol/l; P2hBG: -3.4 mmol/l vs -3.7 mmol/l vs -3.2 mmol/l). The changes of HbA1c and P2hBG among the three groups had no significance. However, vildagliptin-added group showed the greatest reduction (p < 0.001), while, sitagliptin-added group showed the lowest reduction (p < 0.001) in terms of FPG changes. Proportions of patients achieving HbA1c < 7% at the end were similar in three groups (saxagliptin 59%, vildagliptin 65%, sitagliptin 59%). Mild hypoglycemia was commonly reported among the three groups (saxagliptin 6%, vildagliptin 2%, sitagliptin 3%). No significant between-group difference was shown in other AEs. Conclusion The three gliptins showed almost similar glycemic control and incidence of adverse events. However, for FBG control, saxagliptin demonstrated superiority to sitagliptin, while, inferiority to vildagliptin.
    Diabetology and Metabolic Syndrome 05/2014; 6:69. DOI:10.1186/1758-5996-6-69 · 2.50 Impact Factor
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