GLP-1 based therapies: clinical implications for gastroenterologists

The gut-derived incretin hormone, glucagon-like peptide 1 (GLP-1) lowers postprandial blood glucose levels by stimulating insulin and inhibiting glucagon secretion. Two novel antihyperglycaemic drug classes augment these effects; GLP-1 receptor agonists and inhibitors of the GLP-1 degrading enzyme dipeptidyl peptidase 4. These so called GLP-1 based or incretin based drugs are increasingly used to treat type 2 diabetes, because of a low risk of hypoglycaemia and favourable effect on body weight, blood pressure and lipid profiles. Besides glucose control, GLP-1 functions as an enterogastrone, causing a wide range of GI responses. Studies have shown that endogenous GLP-1 and its derived therapies slow down digestion by affecting the stomach, intestines, exocrine pancreas, gallbladder and liver. Understanding the GI actions of GLP-1 based therapies is clinically relevant; because GI side effects are common and need to be recognised, and because these drugs may be used to treat GI disease.
Source: Gut - Category: Gastroenterology Authors: Tags: GUT Recent advances in clinical practice, Pancreas and biliary tract, Editor's choice, Stomach and duodenum Source Type: research

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Authors: Davis EM, Sandoval DA Abstract GLP-1 was described as an incretin over 30 years ago. GLP-1 is encoded by the preproglucagon gene (Gcg), which is expressed in the intestine, the pancreas, and the central nervous system. GLP-1 activates GLP-1 receptors (GLP-1r) on the β-cell to induce insulin secretion in a glucose-dependent manner. GLP-1 also inhibits α-cell secretion of glucagon. As few, if any, GLP-1r are expressed on α-cells, indirect regulation, via β- or δ-cell products has been thought to be the primary mechanism by which GLP-1 inhibits glucagon secretion. However, recent w...
Source: Comprehensive Physiology - Category: Physiology Tags: Compr Physiol Source Type: research
Publication date: January 2020Source: Biomedical and Environmental Sciences, Volume 33, Issue 1Author(s): Lu XU, Shu Qing YU, Le GAO, Yi HUANG, Shan Shan WU, Jun YANG, Yi Xin SUN, Zhi Rong YANG, San Bao CHAI, Yuan ZHANG, Li Nong JI, Feng SUN, Si Yan ZHAN
Source: Biomedical and Environmental Sciences - Category: Biomedical Science Source Type: research
Conclusions: This meta-analysis revealed a significant association between pancreatitis and DPP-4 inhibitors; however, no such association was observed for GLP-1RAs. PMID: 32129106 [PubMed - as supplied by publisher]
Source: Expert Review of Clinical Pharmacology - Category: Drugs & Pharmacology Tags: Expert Rev Clin Pharmacol Source Type: research
ConclusionsTo our knowledge, no study has examined the detailed dynamic changes in glucose and insulin homeostasis in this number of participants undergoing SG in relation to incretin hormones GIP and GLP-1. This current study supports the role of SG for the treatment of obesity-related glucose dysregulation.
Source: Obesity Surgery - Category: Surgery Source Type: research
Publication date: Available online 14 February 2020Source: Pharmacology &TherapeuticsAuthor(s): Shiying Shao, QinQin Xu, Xuefeng Yu, Ruping Pan, Yong ChenAbstractDipeptidyl peptidase 4 (DPP4) inhibitors (DPP4is) are oral anti-diabetic drugs (OADs) for the treatment of type 2 diabetes mellitus (T2DM) through inhibiting the degradation of incretin peptides. Numerous investigations have been focused on the effects of DPP4is on glucose homeostasis. However, there are limited evidences demonstrating their Potential modulatory functions in the immune system. DPP4, originally known as the lymphocyte cell surface protein CD26,...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research
AbstractGender and biological sex impact the pathogenesis of numerous diseases, including metabolic disorders such as diabetes. In most parts of the world, diabetes is more prevalent in men than in women, especially in middle-aged populations. In line with this, considering almost all animal models, males are more likely to develop obesity, insulin resistance and hyperglycaemia than females in response to nutritional challenges. As summarised in this review, it is now obvious that many aspects of energy balance and glucose metabolism are regulated differently in males and females and influence their predisposition to type ...
Source: Diabetologia - Category: Endocrinology Source Type: research
ConclusionsThere were rapid changes within 4 weeks after RYGB: signs of enhanced parasympathetic nerve activity, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose. The findings suggest that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in type 2 diabetes.
Source: Endocrine - Category: Endocrinology Source Type: research
Publication date: Available online 23 January 2020Source: Pharmacological ResearchAuthor(s): Shabnam Radbakhsh, Thozhukat Sathyapalan, Maciej Banach, Amirhossein SahebkarAbstractMicroRNAs (miRNA) are one class of the small regulatory RNAs that can impact the expression of numerous genes including incretin hormones and their G protein-coupled receptors. Incretin peptides, including GLP-1, GLP-2, and GIP, are released from the gastrointestinal tract and have an crucial role in the glucose hemostasis and pancreatic beta-cell function. These hormones and their analogs with a longer half-life, glucagon like peptide-1 receptor a...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
ConclusionTherefore, our results demonstrate that DA5 ‐CH has neuroprotective effects in the STZ‐induced animal model and that DA5‐CH has potential to treat neurodegenerative disorders such as AD.
Source: Brain and Behavior - Category: Neurology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Conclusion: GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable. PMID: 32029057 [PubMed - in process]
Source: Biomedical and Environmental Sciences : BES - Category: Biomedical Science Authors: Tags: Biomed Environ Sci Source Type: research
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