Página 1 dos resultados de 247 itens digitais encontrados em 0.001 segundos

Análise da resposta hormonal pancreática antes e após tratamento com GLP-1 mimético em indivíduos com diabetes tipo 2 portadores da variante rs7903146 do gene TCF7L2; Analysis of pancreatic hormonal response before and after treatment with GLP-1-mimetic in subjects with type 2 diabetes carrying the rs7903146 variant in TCF7L2

Ferreira, Mari Cassol
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 03/10/2013 Português
Relevância na Pesquisa
27.97192%
Introdução: O gene TCF7L2 (Transcription Factor 7-Like 2) codifica o fator de transcrição de mesmo nome que, tem importante papel na via Wnt de sinalização intra celular. A via Wnt é constituída por proteínas de integração e ligação dos processos de diferenciação e multiplicação celulares, interagindo com os fatores TCF, e ativando a expressão de genes relacionados ao TCF7L2, sendo este amplamente expresso em vários tecidos. Dados epidemiológicos atuais não deixam dúvidas quanto à forte associação de polimorfismos do gene TCF7L2 com o diabetes tipo 2 (DM2) em diferentes etnias. Apesar de serem pouco conhecidos os mecanismos que envolvem o gene TCF7L2 no DM2, tem sido bem demonstrada a associação do alelo T no rs7903146 com redução da secreção de insulina, redução do efeito das incretinas, principalmente do GLP-1, aumento na secreção de glucagon e a longo prazo, redução da meia vida da célula beta. Em vista destas evidências, aventamos a hipótese de que pacientes com DM2 portadores da variante rs7903146 do gene TCF7L2, ao ser tratados com GLP-1 mimético, poderiam responder de forma peculiar. Objetivos: Avaliar a resposta hormonal pancreática antes e após tratamento com GLP-1 mimético em indivíduos com DM2 portadores da variante rs7903146 do gene TCF7L2. Pacientes e Métodos: Foram genotipados162 indivíduos com DM2 portadores da variante rs7903146 do gene TCF7L2: idade (57...

Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease

Fan,Hui; Pan,QingRong; Xu,Yuan; Yang,XinChun
Fonte: Sociedade Brasileira de Endocrinologia e Metabologia Publicador: Sociedade Brasileira de Endocrinologia e Metabologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2013 Português
Relevância na Pesquisa
37.790703%
OBJECTIVE: To investigate the effects of exenatide on blood glucose, body weight and hepatic enzymes in patients with type 2 diabetes mellitus (T2DM) and concomitant non-alcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS: One hundred and seventeen patients with T2DM and NAFLD were randomly divided into exenatide group and metformin group. Patients were treated with exenatide and metformin, respectively, for 12 weeks. RESULTS: After 12 weeks of treatment, body weight, body mass index (BMI), waist-to-hip ratio, HbA1c, FPG, 2-h PPG, ALT, AST, γ-GT, and hs-CRP were significantly reduced, and the AST/ALT ratio and adiponectin were markedly increased in both groups. BMI, waist-to-hip ratio, 2-h PPG, ALT, AST, γ-GT, and hs-CRP were markedly lower, and AST/ALT ratio and adiponectin in the exenatide group were dramatically higher than in the metformin group. CONCLUSION: Compared with metformin, exenatide is better to control blood glucose, reduces body weight and improves hepatic enzymes, attenuating NAFLD in patients with T2DM concomitant with NAFLD.

Exenatide can reduce glucose independent of islet hormones or gastric emptying

Ionut, Viorica; Zheng, Dan; Stefanovski, Darko; Bergman, Richard N.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
28.011023%
Exenatide is a long-acting glucagon-like peptide-1 (GLP-1) mimetic used in the treatment of type 2 diabetes. There is increasing evidence that GLP-1 can influence glycemia not only via pancreatic (insulinotropic and glucagon suppression) and gastric-emptying effects, but also via an independent mechanism mediated by portal vein receptors. The aim of our study was to investigate whether exenatide has an islet- and gastric-independent glycemia-reducing effect, similar to GLP-1. First, we administered mixed meals, with or without exenatide (20 μg sc) to dogs. Second, to determine whether exenatide-induced reduction in glycemia is independent of slower gastric emptying, in the same animals we infused glucose intraportally (to simulate meal test glucose appearance) with exenatide, exenatide + the intraportal GLP-1 receptor antagonist exendin-(9-39), or saline. Exenatide markedly decreased postprandial glucose: net 0- to 135-min area under the curve = +526 ± 315 and −536 ± 197 mg·dl−1·min−1 with saline and exenatide, respectively (P < 0.05). Importantly, the decrease in plasma glucose occurred without a corresponding increase in postprandial insulin but was accompanied by delayed gastric emptying and lower glucagon. Significantly lower glycemia was induced by intraportal glucose infusion with exenatide than with saline (92 ± 1 vs. 97 ± 1 mg/dl...

Exenatide does not evoke pancreatitis and attenuates chemically induced pancreatitis in normal and diabetic rodents

Tatarkiewicz, Krystyna; Smith, Pamela A.; Sablan, Emmanuel J.; Polizzi, Clara J.; Aumann, Donald E.; Villescaz, Christiane; Hargrove, Diane M.; Gedulin, Bronislava R.; Lu, Melissa G. W.; Adams, Lisa; Whisenant, Tina; Roy, Denis; Parkes, David G.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.97192%
The risk of developing pancreatitis is elevated in type 2 diabetes and obesity. Cases of pancreatitis have been reported in type 2 diabetes patients treated with GLP-1 (GLP-1R) receptor agonists. To examine whether the GLP-1R agonist exenatide potentially induces or modulates pancreatitis, the effect of exenatide was evaluated in normal or diabetic rodents. Normal and diabetic rats received a single exenatide dose (0.072, 0.24, and 0.72 nmol/kg) or vehicle. Diabetic ob/ob or HF-STZ mice were infused with exenatide (1.2 and 7.2 nmol·kg−1·day−1) or vehicle for 4 wk. Post-exenatide treatment, pancreatitis was induced with caerulein (CRN) or sodium taurocholate (ST), and changes in plasma amylase and lipase were measured. In ob/ob mice, plasma cytokines (IL-1β, IL-2, IL-6, MCP-1, IFNγ, and TNFα) and pancreatitis-associated genes were assessed. Pancreata were weighed and examined histologically. Exenatide treatment alone did not modify plasma amylase or lipase in any models tested. Exenatide attenuated CRN-induced release of amylase and lipase in normal rats and ob/ob mice but did not modify the response to ST infusion. Plasma cytokines and pancreatic weight were unaffected by exenatide. Exenatide upregulated Reg3b but not Il6...

Critical appraisal of once-weekly formulation of exenatide in the control of type 2 diabetes mellitus

Seewoodhary, Jason; Griffin, Leanne; Bain, Stephen C
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Artigo de Revista Científica
Publicado em 17/05/2010 Português
Relevância na Pesquisa
28.011023%
Exenatide (also known as exendin-4) is a glucagon-like peptide-1 mimetic, which is indicated for the treatment of type 2 diabetes mellitus. The currently available formulation of this drug is a twice-daily exenatide (exenatide BID) injection that should be administered within 60 minutes of food. Once-weekly exenatide (exenatide QW) formulation is now being assessed in a clinical trial program. Exenatide QW has been shown to be the only noninsulin monotherapy to achieve glycosylated hemoglobin levels of <7% in >75% of treated patients. It has also demonstrated potential cardiovascular benefits by lowering total and low-density lipoprotein cholesterol concentrations, triglyceride levels, and both systolic and diastolic blood pressure. In addition, patients treated with exenatide QW achieved significant weight loss, which may also lead to significant cardiovascular risk reduction. Exenatide QW is associated with a lower incidence of gastrointestinal adverse effects compared with exenatide BID, and no patients treated with exenatide QW monotherapy experienced a confirmed hypoglycemic event. Exenatide QW results in 24-hour coverage with exenatide concentrations that are known to improve glycemic control and remain well tolerated in patients with type 2 diabetes mellitus. This review defines the state of play with exenatide QW by critically appraising its role in clinical practice.

Recent results of exenatide use as adjunctive therapy in the treatment of patients with type 2 diabetes

Odegard, Peggy Soule; DeSantis, Anthony
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Artigo de Revista Científica
Publicado em 31/07/2009 Português
Relevância na Pesquisa
27.790703%
Exenatide is a GLP-1 receptor agonist approved for use in type 2 diabetes mellitus. In clinical trials, significant reductions in serum glucose and weight were demonstrated for exenatide with primary glycemic effects of the twice daily formulation on prandial glucose control. In this paper, we review recent research with exenatide as adjunctive therapy in type 2 diabetes mellitus. In particular, studies demonstrate ongoing benefit on glycemic control and weight reduction with continued therapy up to 82 weeks duration and efficacy as adjunctive therapy for patients taking metformin, thiazolidinediones, and/or a sulfonylurea and as compared to sitagliptin and various insulin formulations. Compared to insulin, exenatide likely has greatest benefit for those patients who are overweight or who need improved prandial glucose control. The new long-acting release formulation of exenatide has demonstrated slightly improved efficacy compared to the twice daily formulation as well as a reduction in gastrointestinal side effects. Emerging research is further exploring novel benefits of exenatide as adjunctive DM therapy, effects on prandial glycemic control, markers of hepatic inflammation, alternative dosage forms including intra-nasal administration...

Exenatide improves glucocorticoid-induced glucose intolerance in mice

Zhao, Ruiying; Fuentes-Mattei, Enrique; Velazquez-Torres, Guermarie; Su, Chun-Hui; Chen, Jian; Lee, Mong-Hong; Yeung, Sai-Ching Jim
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Artigo de Revista Científica
Publicado em 26/01/2011 Português
Relevância na Pesquisa
27.97192%
Exenatide is an incretin mimetic that is recently available in the US for the treatment of diabetes. There is a paucity of information on the effects of exenatide in glucocorticoid (GC)-induced diabetes. Although the effect of continuous intravenous infusion of exenatide on GC-induced glucose intolerance has been investigated before in healthy human males receiving oral prednisolone, we investigated the efficacy of a single subcutaneous dose of exenatide (3 μg/kg) in lowering blood glucose in GC-induced glucose intolerance in C57BL/6 mice. In a longitudinal experiment, the area under the curve (AUC) of oral glucose tolerance tests (OGTT) significantly increased after dexamethasone (P = 0.004), which was subsequently decreased by exenatide (P < 0.001). A cross-sectional experiment showed that exenatide improved glucose tolerance compared with placebo in a mouse model of dexamethasone-induced glucose intolerance. AUC of OGTT in the exenatide group were significantly (P < 0.001) lower than in the placebo group. Insulin tolerance tests (ITT) demonstrated that exenatide decreased the ability of the mice to tolerate insulin compared with placebo. The AUC of ITT in the exenatide group were also significantly (P = 0.006) lower than in the placebo group. In conclusion...

Exenatide Pretreatment Improved Graft Function in Nonhuman Primate Islet Recipients Compared to Treatment after Transplant Only

Buss, Jill L.; Rajab, Amer; Essig, Elizabeth D.; Bergdall, Valerie K.; Wang, Jie; Osei, Kwame
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.842705%
The GLP-1 receptor agonist, exenatide, has previously been shown to improve insulin secretion, protect beta cells from apoptosis, and promote beta cell regeneration. We propose that pretreatment with exenatide will promote islet graft survival and improve graft function. Pancreatectomized cynomolgus monkeys underwent islet allotransplantation and were treated with exenatide beginning on day 0 or day −2. A third group of animals was treated with an immunosuppressive regimen while a fourth group remained untreated. Fasting blood glucose (FBG) was used to evaluate graft function along with intravenous glucose tolerance tests (IVGTTs) performed at study endpoint (day 10 for untreated and posttransplant exenatide or day 90 for pretreatment exenatide and immunosuppression). The average FBG for pre-treated animals day 5 following transplant was 52.7 ± 14.8 mg/dl, compared to 154.3 ± 105.5 mg/dl for animals treated only following transplant, 59.4 mg/dl ±12.1 for animals treated with immunosuppression, and 265.5 ± 172.3 mg/dl for untreated animals. IVGTTs performed at study endpoint showed normal glucose and insulin curves in the pre-treated exenatide and immunosuppression groups only, with beta cell function actually improving after transplant in the pre-treated group. We conclude...

Evolution of Exenatide as a Diabetes Therapeutic

Bhavsar, Sunil; Mudaliar, Sunder; Cherrington, Alan
Fonte: Bentham Science Publishers Publicador: Bentham Science Publishers
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.842705%
Type 2 diabetes (T2DM) is a disease of epidemic proportion associated with significant morbidity and excess mortality. Optimal glucose control reduces the risk of microvascular and possibly macrovascular complications due to diabetes. However, glycemic control is rarely optimal and several therapeutic interventions for the treatment of diabetes cause hypoglycemia and weight gain; some may exacerbate cardiovascular risk. Exenatide (synthetic exendin-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist developed as a first-in-class diabetes therapy. This review presents an overview of the evolution of exenatide as a T2DM treatment, beginning with the seminal preclinical discoveries and continuing through to clinical pharmacology investigations and phase 3 clinical trials. In patients with T2DM, exenatide enhanced glucose-dependent insulin secretion, suppressed inappropriately elevated glucagon secretion, slowed gastric emptying, and enhanced satiety. In controlled phase 3 clinical trials ranging from 12 to 52 weeks, 10-mcg exenatide twice daily (ExBID) reduced mean HbA1c by -0.8% to -1.7% as monotherapy or in combination with metformin (MET), sulfonylureas (SFU), and/or thiazolidinediones (TZD); with mean weight losses of -1.2 kg to -8.0 kg. In controlled phase 3 trials ranging from 24 to 30 weeks...

Alleviation of Hyperglycemia Induced Vascular Endothelial Injury by Exenatide Might Be Related to the Reduction of Nitrooxidative Stress

Zhao, Qian; Xu, Chun-ling; Xiong, Hai-yan; Huang, Wen; Zhang, Mei; Wang, Yun; Wang, Si-yu; Wang, Wen
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.88451%
We will investigate the effects of exenatide on vascular endothelial injury and nitrooxidative stress in hyperglycemia both in vivo and in vitro and explore the role of nitrooxidative stress in endothelium-protective action of exenatide. Healthy male Wistar rats were randomly divided into 4 groups: control, diabetes mellitus (DM) model, low dose of exenatide treatment, and high dose of exenatide treatment. In vitro study showed that, compared with control group, the DM rats exhibited a lowered endothelium-dependent relaxation and damaged structural integrity of thoracic aortas, and there was a significant increase in plasma nitrotyrosine concentration. These parameters were improved after treatment with either low dose or high dose of exenatide for 45 days. In vitro study showed that exendin-4 (the active ingredient of exenatide) attenuated HUVECs injury induced by high glucose, with improving cell viability and attenuating cell apoptosis. Exendin-4 also significantly alleviated the increased malondialdehyde (MDA), nitrotyrosine content, and inducible nitric oxide synthase (iNOS) expression induced by high glucose in HUVECs. In conclusion, this study demonstrates that exenatide treatment can alleviate the vascular endothelial injury...

Oral Delivery of Exenatide via Microspheres Prepared by Cross-Linking of Alginate and Hyaluronate

Zhang, Baojie; He, Dongyang; Fan, Yu; Liu, Nan; Chen, Yijun
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 21/01/2014 Português
Relevância na Pesquisa
27.842705%
Exenatide is an FDA-approved glucose-lowering peptide drug for the treatment of type 2 diabetes by subcutaneous injection. To address the issues on the inconvenience for patient use and the difficulty of oral administration of peptide drugs, chemical cross-linking of two pH-responsive biomaterials, alginate and hyaluronate, was carried out to prepare a new material for the encapsulation of exenatide as a form of microspheres. The exenatide-loaded microspheres exhibited spherical structures with excellent loading and release behaviors in the simulated gastrointestinal tract environments. After oral administration of the microspheres in db/db mice, maximum plasma concentration of exenatide appeared at 4 hours, and blood glucose was effectively reduced to a normal level within 2 hours and maintained for another 4 hours. The bioavailability of the exenatide-loaded microspheres, relative to subcutaneous injection of exenatide, reached 10.2%. Collectively, the present study demonstrated the feasibility of orally delivering exenatide with the new cross-linked biomaterial and formulation, and showed therapeutic potential for clinical applications.

Novel Exenatide Analogs with Peptidic Albumin Binding Domains: Potent Anti-Diabetic Agents with Extended Duration of Action

Levy, Odile E.; Jodka, Carolyn M.; Ren, Shijun Steven; Mamedova, Lala; Sharma, Abhinandini; Samant, Manoj; D’Souza, Lawrence J.; Soares, Christopher J.; Yuskin, Diane R.; Jin, Li Jenny; Parkes, David G.; Tatarkiewicz, Krystyna; Ghosh, Soumitra S.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 04/02/2014 Português
Relevância na Pesquisa
28.026953%
The design, synthesis and pharmacology of novel long-acting exenatide analogs for the treatment of metabolic diseases are described. These molecules display enhanced pharmacokinetic profile and potent glucoregulatory and weight lowering actions compared to native exenatide. [Leu14]exenatide-ABD is an 88 residue peptide amide incorporating an Albumin Binding Domain (ABD) scaffold. [Leu14]exenatide-ABP is a 53 residue peptide incorporating a short Albumin Binding Peptide (ABP). [Leu14]exenatide-ABD and [Leu14]exenatide-ABP exhibited nanomolar functional GLP-1 receptor potency and were metabolically stable in vitro in human plasma and in a pancreatic digestive enzyme mixture. Both molecules displayed picomolar and nanomolar binding association with albumin across multiple species and circulating half lives of 16 and 11 hours, respectively, post a single IV dose in rats. Unlike exenatide, both molecules elicited robust glucose lowering when injected 1 day prior to an oral glucose tolerance test, indicative of their extended duration of action. [Leu14]exenatide-ABD was compared to exenatide in a Lep ob/ob mouse model of diabetes. Twice-weekly subcutaneously dosed [Leu14]exenatide-ABD displayed superior glucose lowering and weight loss in diabetic mice when compared to continuously infused exenatide at the same total weekly dose. A single oral administration of each molecule via an enteric coated capsule to cynomolgus monkeys showed superior pharmacokinetics for [Leu14]exenatide-ABD as compared to [Leu14]exenatide-ABP with detectable exposure longer than 14 days. These studies support the potential use of these novel long acting exenatide analogs with different routes of administration for the treatment of type 2 diabetes.

Combined antidiabetic benefits of exenatide and dapagliflozin in diabetic mice†

Tatarkiewicz, K; Polizzi, C; Villescaz, C; D’Souza, L J; Wang, Y; Janssen, S; Parkes, D G
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
28.011023%
The combined glucose-lowering effect of exenatide and dapagliflozin has not yet been studied. We investigated this combination (single-dose or 4-week dosing) in diabetic ob/ob mice. Vehicle-corrected basal glucose showed greater reduction 1 h following exenatide + dapagliflozin than with exenatide or dapagliflozin alone, and stayed significantly lower for all groups versus vehicle over 3 h. During an oral glucose tolerance test, glucose excursion (30 min post-dose) was significantly lower for exenatide + dapagliflozin versus exenatide or dapagliflozin, or vehicle. Exenatide + dapagliflozin and exenatide, but not dapagliflozin alone, reduced glucose excretion over 24 h versus vehicle. After dosing for 4 weeks, exenatide, dapagliflozin and exenatide + dapagliflozin similarly decreased haemoglobin A1c (HbA1c). Body weight was reduced only with exenatide or exenatide + dapagliflozin. The glomerular filtration rate was similar with exenatide, dapagliflozin and vehicle, and increased with exenatide + dapagliflozin. Optimized combinatorial dosing of these antidiabetic agents may provide additive glucose lowering in type 2 diabetes mellitus.

Determining Predictors of Early Response to Exenatide in Patients with Type 2 Diabetes Mellitus

Khan, Muhammad; Ouyang, Jing; Perkins, Karen; Nair, Sunil; Joseph, Franklin
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.918848%
Exenatide is a GLP-1 analogue used in the management of T2DM yet within a subset of patients fails due to adverse side effects or from failure to attain the end goal. This retrospective observational study aimed to determine whether we could predict response to exenatide in patients with T2DM. 112 patients on exenatide were included with patient age, gender, duration of T2DM, medications alongside exenatide and weight, BMI, and HbA1c at baseline and 3 and 6 months of exenatide use being recorded. 63 responded with 11 mmol/mol reduction from baseline HbA1c after six months and 49 did not respond to exenatide. HbA1c solely differed significantly between cohorts at baseline, 3 months, and 6 months (P < 0.05). Regression analyses identified a negative linear relationship with higher baseline HbA1c correlating to greater reductions in HbA1c by 6 months (P < 0.0001). HbA1c was the sole predictor of exenatide response with higher baseline HbA1c increasing the odds of response by 5% (P = 0.004). Patients with HbA1c reductions ≥15–20% by 3 months were more likely to be responders by 6 months (P = 0.033). Our study identified that baseline HbA1c acted as the sole predictor of exenatide response and that response may be determined after 3 months of exenatide administration.

Proteomic Analysis of INS-1 Rat Insulinoma Cells: ER Stress Effects and the Protective Role of Exenatide, a GLP-1 Receptor Agonist

Kim, Mi-Kyung; Cho, Jin-Hwan; Lee, Jae-Jin; Son, Moon-Ho; Lee, Kong-Joo
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 20/03/2015 Português
Relevância na Pesquisa
27.88451%
Beta cell death caused by endoplasmic reticulum (ER) stress is a key factor aggravating type 2 diabetes. Exenatide, a glucagon-like peptide (GLP)-1 receptor agonist, prevents beta cell death induced by thapsigargin, a selective inhibitor of ER calcium storage. Here, we report on our proteomic studies designed to elucidate the underlying mechanisms. We conducted comparative proteomic analyses of cellular protein profiles during thapsigargin-induced cell death in the absence and presence of exenatide in INS-1 rat insulinoma cells. Thapsigargin altered cellular proteins involved in metabolic processes and protein folding, whose alterations were variably modified by exenatide treatment. We categorized the proteins with thapsigargin initiated alterations into three groups: those whose alterations were 1) reversed by exenatide, 2) exaggerated by exenatide, and 3) unchanged by exenatide. The most significant effect of thapsigargin on INS-1 cells relevant to their apoptosis was the appearance of newly modified spots of heat shock proteins, thimet oligopeptidase and 14-3-3β, ε, and θ, and the prevention of their appearance by exenatide, suggesting that these proteins play major roles. We also found that various modifications in 14-3-3 isoforms...

Exenatide once-weekly injection for the treatment of type 2 diabetes in Chinese patients: current perspectives

Deng, Wuquan; Qiu, Sheng; Yang, Gangyi; Chen, Bing
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Artigo de Revista Científica
Publicado em 10/08/2015 Português
Relevância na Pesquisa
27.947559%
Glucagon-like peptide-1 (GLP-1) analogs, such as exenatide, have played an important role as antidiabetic medications in the treatment of type 2 diabetes (T2DM). Like most other hypoglycemic agents, exenatide has a number of actions, including lowering blood glucose, promoting weight loss, improving insulin resistance, and protecting islet β-cells. Although GLP-1 analogs, combined with other antidiabetic medications, have excellent performance in T2DM, some side effects and imperfections limit its use in clinical practice. Since 2012, a new generation GLP-1 agent, exenatide once weekly (QW), has been available for patients with T2DM in the USA, but not as yet in the People’s Republic of China. Previous data indicate that exenatide QW achieves better fasting glucose reductions than sitagliptin or exenatide twice daily, whilst appearing non-inferior to pioglitazone and achieving less reductions than insulin glargine. Exenatide QW was better at improving average postprandial glucose than sitagliptin or titrated insulin glargine, but was inferior to exenatide twice daily. Additionally exenatide QW has a better effect in terms of weight loss than other glycemic medications. Exenatide QW can also reduce blood lipids and lower blood pressure. Accordingly...

Effect of exenatide on gastric emptying and relationship to postprandial glycemia in type 2 diabetes

Linnebjerg, H.; Park, S.; Kothare, P.; Trautmann, M.; Mace, K.; Fineman, M.; Wilding, I.; Nauck, M.; Horowitz, M.
Fonte: Elsevier Science BV Publicador: Elsevier Science BV
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
Relevância na Pesquisa
37.992847%
OBJECTIVES: To evaluate the effect of exenatide on gastric emptying (GE) in type 2 diabetes using scintigraphy. METHODS: Seventeen subjects with type 2 diabetes participated in a randomized, single-blind, 3-period, crossover study. In each 5-day period, 5 or 10 microg exenatide or placebo was administered subcutaneously BID. Oral antidiabetic treatments were continued. The presence of cardiac autonomic neuropathy was assessed during screening. On day 5, after the morning dose, subjects consumed a 450-kcal breakfast containing (99m)Tc-labeled eggs and (111)In-labeled water, and GE was measured by scintigraphy. Plasma glucose and insulin, perceptions of appetite, and plasma exenatide were also quantified. RESULTS: Exenatide slowed GE of both solid and liquid meal components [solid (T(50)(90% confidence interval [CI]); placebo, 60(50-70) min; 5 microg exenatide, 111(94-132) min; 10 microg exenatide, 169(143-201) min; both P<0.01); liquid (T(50)(90% CI), placebo, 34(25-46) min; 5 microg exenatide, 87(65-117) min; 10 microg exenatide, 114(85-154) min; both P<0.01)]. GE was not different between subjects with cardiac autonomic neuropathy (n=7), compared with those without (n=10) (P>/=0.68). Exenatide reduced postprandial glucose (area under the curve [AUC((0-6 h))]) by 69-76% and peak insulin (C(max)) by 84-86% compared with placebo. There was an inverse relationship between the postprandial rise in glucose (AUC((0-3 h))) and GE (solid T(50)...

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats

Rudinsky, A. J.; Adin, C. A.; Borin-Crivellenti, S.; Rajala-Schultz, P.; Hall, M. J.; Gilor, C.
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 78-85
Português
Relevância na Pesquisa
37.918848%
Exenatide extended-release (ER) is a microencapsulated formulation of the glucagon-like peptide 1-receptor agonist exenatide: It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin with an improved safety profile in type II diabetic people. Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target = 225 mg/dL) was performed on days 7 (clamp I) and 21 (clamp II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean standard deviation = 11 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% 14%-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%-12.1%], P = 0.005). Compared with preinjection values on continuous glucose monitoring...

Exenatide in obesity with accelerated gastric emptying: a randomized, pharmacodynamics study

Acosta, Andres; Camilleri, Michael; Burton, Duane; O’Neill, Jessica; Eckert, Deborah; Carlson, Paula; Zinsmeister, Alan R
Fonte: John Wiley & Sons, Ltd Publicador: John Wiley & Sons, Ltd
Tipo: Artigo de Revista Científica
Publicado em 29/10/2015 Português
Relevância na Pesquisa
27.88451%
Obesity is associated with differences in satiety, gastric emptying (GE), gastric volume, and psychological traits. Exenatide, a short-acting glucagon-like peptide 1 (GLP-1) receptor agonist, is associated with variable weight loss. We compared the effects of exenatide, 5 μg, and placebo SQ, twice daily for 30 days on GE of solids and liquids (scintigraphy), satiety (ad libitum buffet meal), satiation (nutrient drink test, maximum tolerated volume [MTV]), and weight loss in 20 participants with documented accelerated GE of solids (T1/2 < 90 min). Exenatide delayed GE of solids (T1/2 [Δ] 86 min relative to placebo, P < 0.001) and reduced calorie intake at buffet meal ([Δ] 129 kcal compared to placebo). Median weight loss was −0.95 kg (IQR −0.7 to −2.1) for exenatide and −0.55 kg (0.3 to −2.1) for placebo (P = 0.23); 80% of exenatide group had documented reduction in weight. In the exenatide treatment group, there was an inverse correlation between gastric emptying T1/2 and MTV (R = −0.548, P = 0.089). The univariate association of weight change with posttreatment MTV was borderline (Rs = 0.43, P = 0.06); in the multiple regression model, posttreatment MTV was associated with weight change (P = 0.047). The effect of the short-acting GLP-1 receptor agonist...

Coste-efectividad de la insulina de acción intermedia o larga contra Exenatide en pacientes con diabetes mellitus tipo 2 no óptimamente controlados con antidiabéticos orales

Edwards,Krystal L.; Irons,Brian K.; Xu,Tom
Fonte: Pharmacy Practice (Granada) Publicador: Pharmacy Practice (Granada)
Tipo: info:eu-repo/semantics/article; journal article; info:eu-repo/semantics/publishedVersion Formato: text/html; application/pdf
Publicado em 01/09/2006 Português
Relevância na Pesquisa
37.790703%
Objetivo: Comprender el papel del exenatide en el tratamiento de la diabetes tipo 2, analizando su coste-efectividad comparado con insulina intermedia (NPH) y de larga duración (glargina). Exetanide es una medicación recientemente aprobada para el tratamiento del a diabetes tipo 2, para ser usada además de los antidiabétios orales frecuentemente usados. Métodos: Para evaluar apropiadamente el coste-efectividad de las insulinas comparadas con exenatide, tanto en control glucémico como de peso, se identificaron dos estudios en una búsqueda en Medline (1996 a octubre 2005) que eran similares en duración, control de la glucemia basal, tamaño de la población y resultados principales. Resultados: Tanto la NPH como la glergina parecen ser más coste-efectivos que el exenatide en relación al control glucémico (ratio CE incremental -1968 y -65520 respectivamente). El exenatide parece ser más coste-efectivo para la reducción del peso corporal que la NPH (Ratio CE 235) o la gargina (ratio CE 128). Conclusiones: Comparada con la insulina intermedia y de larga duración, exenatide no parece ser más coste-efectivo para el tratamiento de la diabetes tipo 2.