Incretin Based Therapies
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Incretin Based Therapies
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Author : Sanjay Kalra
language : en
Publisher: JP Medical Ltd
Release Date : 2013-03-31
Incretin Based Therapies written by Sanjay Kalra and has been published by JP Medical Ltd this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-03-31 with Medical categories.
Incretins are a group of gastrointestinal hormones that cause an increase in the amount of insulin released from cells in the pancreas after eating. Incretin based drugs are used to control blood sugar levels in the management of diabetes. This book is a concise guide to incretin based therapy. Beginning with an introduction to the history and physiology of incretins, the following sections examine the clinical pharmacology of GLP-1 Analogues and DPP-4 Inhibitors, the pleiotrophic effects of incretins and comparative pharmacology. Each section integrates science with practical therapeutic guidance for clinicians involved in the management of diabetes. The final chapter discusses the future of incretin therapies, including non-diabetic usage and combination therapy. Key Features Concise overview of incretin based therapy for the management of diabetes Guides clinicians step by step through the history and pharmacology of various molecules Integrates science with practical therapeutic guidance Includes chapter on the future of incretin therapy
Handbook Of Incretin Based Therapies In Type 2 Diabetes
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Author : Stephen Gough
language : en
Publisher: Springer
Release Date : 2016-06-07
Handbook Of Incretin Based Therapies In Type 2 Diabetes written by Stephen Gough and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-06-07 with Medical categories.
This concise handbook provides an overview of incretin-based therapies and guidance for incorporating them into the treatment of type 2 diabetes. Chapters include landmark clinical trials and international treatment guidelines in order to update readers with all major advances in the field. An ideal resource for medical professionals that treat patients with type 2 diabetes in hospital and clinical settings.
Novel Incretin Based Therapies For Type 2 Diabetes And Obesity
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Author : Barry Kerr
language : en
Publisher:
Release Date : 2011
Novel Incretin Based Therapies For Type 2 Diabetes And Obesity written by Barry Kerr and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.
Gut peptides including glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-l (GLP-I), and oxyntomodulin (Oxm) act to regulate glucose homeostasis, insulin secretion, bodyweight and satiety. However, clinical development has been hindered by rapid enzymatic degradation followed by renal clearance. This thesis evaluates the biological activities of these peptides, and exploits various chemical modifications / approaches to generate novel mimetics with therapeutic potential for type 2 diabetes and obesity. Acylation of Lys37 in GIP with C-14 fatty acid (myristate) afforded dipeptidylpeptidase-IV (DPP-IV) resistance and significantly enhanced in vitro cAMP production and insulin secretion. Furthermore, administration of N- AcGIP(Lys37 MYR) resulted in markedly improved glucose homeostasis and insulin-release in obese diabetic (ob/ob) mice. Once-daily administration of the DPP- IV resistant GIP analogue, GIP[mPEG], decreased non-fasting plasma glucose concentrations, increased insulin concentrations and improved glycaemic and insulin responses to a glucose load in mice with age-related glucose intolerance. These data clearly demonstrate the utility of stable analogues of GIP for treatment of obesity- diabetes. The GLP-l mimetic, Liraglutide, lacking the y-glutamyl linker (Lira-yGlu) demonstrated equi-potent DPP-IV resistance, cAMP production and insulin secretion compared with Liraglutide. In vivo, Lira-yGlu and Liraglutide significantly lowered plasma glucose in fasted mice. Twice-daily administration of either GLP-l analogue decreased food intake and plasma glucose concentrations, whilst increasing plasma insulin, and improving glucose tolerance and insulin sensitivity. These data indicate lack of requirement of y-glutamyl linker together with acylation for generation of long-acting incretin mimetics. Evaluating the effects of a an overnight preparation of Liraglutide and N- AcGIP(Lys37Myr) (Lira-AcGIP - mixed together and incubated for 12h) revealed improved acute glucose tolerance and insulin responses compared to a simple combination (immediate mixture). Furthermore, daily administration of the Lira- AcGIP preparation lowered bodyweight, decreased food intake, plasma glucose and insulin concentrations in ob/ob mice, as well as enhancing glucose tolerance, insulin response to glucose and insulin content. These data indicate the possibility of using combination therapy with stable GLP-l and GIP mimetics for treatment of type 2 diabetes. Oxm analogues, (0-Ser2)Oxm and (0-Ser2)Oxm[mPEG-PAL] exhibited DPP- IV stability, with equi-potent in vitro cAMP production and insulin secretion. In the presence of specific antagonists, cAMP production was reduced in GLP-l and glucagon receptor transfected cells, consistent with actions of dual receptor agonism. In acute studies, (0-Ser2)Oxm and (0-Ser2)Oxm[mPEG-PAL] exhibited glucoregulatory and anorexigenic properties with (0-Ser2)Oxm[mPEG-PAL] demonstrating more potent actions. Once-daily administration of (0- Ser2)Oxm[mPEG-PAL] decreased food intake, bodyweight and plasma glucose concentrations and increased insulin concentrations in ob/ob mice whilst improving glucose tolerance, insulin response to glucose and plasma lipid profiles. The N-terminal domain of GIP plays an important role in regulating its biological activity. Examining several novel N-terminally truncated forms of GIP revealed that GIP(8-42) exhibited reduced cAMP levels compared to native hormone whilst inhibiting GIP-induced cAMP production. In ob/ob mice, GIP(8-42) increased plasma glucose concentrations compared to the glucose-lowering action of native GIP. When GIP(8-42) was co-administered with GIP it countered the ability of the native hormone to lower plasma glucose and increase insulin concentrations. These data demonstrate the importance of the N-terminal of GIP in regulating bioactivity. Collectively, these data illustrate chemical modifications / approaches to improve the biological efficacy of GIP, GLP-l and Oxm. The use of smaller moieties to offset enzymatic degradation and renal clearance offer improved efficacy potentially due to reduced steric hindrance compared to currently available incretin therapies. In addition, incretin preparations and the dual role of Oxm may offer targeted 'smart therapy' for both obesity and type 2 diabetes. Hopefully this thesis will aid the development of pharmaceutical agents and subsequent clinical studies that will ultimately improve the lives of people suffering from type 2 diabetes and obesity.
The Role Of Incretin Based Therapies In Treating Patients With Type 2 Diabetes Mellitus
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Author : Laurence Kennedy
language : en
Publisher:
Release Date : 2009
The Role Of Incretin Based Therapies In Treating Patients With Type 2 Diabetes Mellitus written by Laurence Kennedy and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009 with categories.
Evaluating The Role Of Incretin Based Therapies In The Management Of Type 2 Diabetes
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Author :
language : en
Publisher:
Release Date : 2011
Evaluating The Role Of Incretin Based Therapies In The Management Of Type 2 Diabetes written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.
Introduction To Biological And Small Molecule Drug Research And Development
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Author : Matthew P. Coghlan
language : en
Publisher: Elsevier Inc. Chapters
Release Date : 2013-05-07
Introduction To Biological And Small Molecule Drug Research And Development written by Matthew P. Coghlan and has been published by Elsevier Inc. Chapters this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-05-07 with Science categories.
The increasing global prevalence of type 2 diabetes represents a significant burden of disease for afflicted patients and for health care systems. In the developed world poorly controlled diabetes is the leading cause of non-traumatic amputation, blindness and end-stage renal disease requiring dialysis and kidney transplant. Additionally, diabetes represents a significant risk factor for the development of cardiovascular disease with its associated morbidity and premature death. Currently available glucose lowering drugs used to treat type 2 diabetes do not impede progression of the disease. Therefore, as the disease progresses these agents rapidly lose efficacy, first as monotherapy and then in combination, resulting in poorly controlled disease. Clearly, there is a significant need for novel glucose lowering drugs for type 2 diabetes that will deliver sustained efficacy over several years by impeding disease progression. Such agents would reduce the risk of developing the microvascular complications of diabetes that ultimately result in amputation, blindness and kidney transplant. Novel glucose lowering drugs should ideally also exhibit a positive impact on the increased cardiovascular risk associated with diabetes. The incretin-based therapies first entered the market in the mid 2000’s and were heralded for their potential to impede progression of type 2 diabetes and to reduce cardiovascular risk. Through mimicking the actions of the gut incretin hormone GLP-1, these drugs had been shown to lower blood glucose in clinical trials by potentiating glucose stimulated insulin secretion from pancreatic β-cells. Moreover, data from preclinical rodent disease models and isolated human pancreatic islets suggested that these novel agents could preserve pancreatic β-cell function and thus impede disease progression. Further preclinical and clinical data supported the notion that these drugs could also aid blood glucose control by suppressing glucagon secretion, slowing gastric emptying and by suppressing appetite. The incretin-based drugs have potential to reduce cardiovascular risk through their ability to reduce body weight, blood pressure and atherogenic blood lipids. This chapter will review the incretin-based therapies and consider what impact these new drugs have made to date in the pharmacotherapy of type 2 diabetes. The incretin-based therapies are of particular relevance to this book as this class of drugs is composed of two sub-classes, injectable peptide drugs and oral small molecule drugs. The similarities and differences between these small molecule and peptide drugs are described.
Incretin Based Therapies
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Author :
language : en
Publisher:
Release Date : 2006
Incretin Based Therapies written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006 with categories.
Neuroprotective And Glucoregulatory Actions Of Incretin Based Therapies In Obesity And Diabetes
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Author : William David Porter
language : en
Publisher:
Release Date : 2011
Neuroprotective And Glucoregulatory Actions Of Incretin Based Therapies In Obesity And Diabetes written by William David Porter and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.
Incretin Based Drugs
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Author : BCC Research
language : en
Publisher:
Release Date : 2015-02
Incretin Based Drugs written by BCC Research and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-02 with categories.
Incretin Based Therapies And The Kidney
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Author :
language : en
Publisher:
Release Date : 2022
Incretin Based Therapies And The Kidney written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022 with categories.
Despite improvements in the management of renal risk factors in type 2 diabetes mellitus patients, and the use of renin-angiotensin-system inhibitors, residual renal risk remains, and novel strategies or new therapeutic options are needed to reduce diabetic kidney disease-burden in this population. After more than a decade of clinical use of incretin-based drugs, the understanding and value of therapeutically engaging glucagon-like peptide (GLP)-1 receptor-mediated mechanisms for type 2 diabetes mellitus treatment are becoming increasingly clear. In addition to glucose-lowering, incretin-based therapies enable maintenance of or reductions in body weight, blood pressure and lipid levels. Such effects, which are not achieved by current standard diabetes care, might help to narrow the gap between recommended and established renal risk factor control in clinical practice. Furthermore, GLP-1 and associated drugs may temporarily increase the renal excretion of electrolytes (most notably sodium), although GLP-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitor treatment does not improve glomerular hyperfiltration in type 2 diabetes mellitus patients with normal renal function. Evidence of pooled analyses, as well as results of large-sized cardiovascular outcome trials indicate that use of some GLP-1 receptor agonists may reduce albuminuria and kidney function loss over time in high-risk patients with type 2 diabetes mellitus, independent of their glucose-lowering effect. DPP-4 inhibitors, in addition to standard care, may modestly improve albuminuria in type 2 diabetes mellitus, plausibly beyond the effects of glycemic control, though their renoprotective efficacy is likely limited and data are inconsistent.