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GLP-1 Analogues

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https://www.readbyqxmd.com/read/29790260/endogenous-glp-1-alters-postprandial-functional-connectivity-between-homeostatic-and-reward-related-brain-regions-involved-in-the-regulation-of-appetite-in-healthy-lean-males-a-pilot-study
#1
Anne Christin Meyer-Gerspach, Huynh Giao Ly, Stefan Borgwardt, Patrick Dupont, Christoph Beglinger, Lukas Van Oudenhove, Bettina K Wölnerhanssen
AIMS: Peripheral infusion of glucagon-like peptide-1 (GLP-1) can affect brain activity in areas involved in the regulation of appetite, including hypothalamic and reward-related brain regions. In contrast, the physiological role of endogenous GLP-1 in the central regulation of appetite has hardly been investigated. MATERIALS AND METHODS: The study was performed as randomized, cross-over trial. Twelve healthy volunteers received an intragastric (ig) glucose (gluc) load with or without intravenous (iv) exendin9-39 (ex9-39; specific GLP-1 receptor antagonist)...
May 22, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29713961/a-systematic-literature-review-and-network-meta-analysis-comparing-once-weekly-semaglutide-with-other-glp-1-receptor-agonists-in-patients-with-type-2-diabetes-previously-receiving-basal-insulin
#2
Michal Witkowski, Lars Wilkinson, Neil Webb, Alan Weids, Divina Glah, Hrvoje Vrazic
INTRODUCTION: Once-weekly semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is currently available as 1.0 mg and 0.5 mg dose for the treatment of type 2 diabetes (T2D). Currently, no head-to-head trial investigating once-weekly semaglutide as an add-on to basal insulin vs other GLP-1 receptor agonists (GLP-1 RAs) is available. The aim of this study was to conduct a network meta-analysis (NMA) to assess the efficacy and safety of once-weekly semaglutide vs other GLP-1 RAs in patients with T2D inadequately controlled on basal insulin...
April 30, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29696037/pharmacological-treatment-in-diabetes-mellitus-type-1-insulin-and-what-else
#3
REVIEW
Ewa Otto-Buczkowska, Natalia Jainta
The basis of treatment in autoimmune diabetes is insulin therapy; however, many clinical cases have proven that this method does not solve all problems. Trials of causal treatment including blocking the autoimmune processes and insulin-producing cells transplants were carried out. Those methods require more research to be concerned as efficient and safe ways of treatment in type 1 diabetes. The use of non-insulin adjunct treatment is a new trend. It has been successfully used in laboratories as well as clinical trials...
January 2018: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29680267/oxyntomodulin-analogue-increases-energy-expenditure-via-the-glucagon-receptor
#4
R Scott, J Minnion, T Tan, S R Bloom
The gut hormone oxyntomodulin (OXM) causes weight loss by reducing appetite and increasing energy expenditure. Several analogues are being developed to treat obesity. Exactly how oxyntomodulin works, however, remains controversial. OXM can activate both glucagon and GLP-1 receptors but no specific receptor has been identified. It is thought that the anorectic effect occurs predominantly through GLP-1 receptor activation but, to date, it has not been formally confirmed which receptor is responsible for the increased energy expenditure...
April 19, 2018: Peptides
https://www.readbyqxmd.com/read/29675798/a-systematic-literature-review-and-network-meta-analysis-comparing-once-weekly-semaglutide-with-other-glp-1-receptor-agonists-in-patients-with-type-2-diabetes-previously-receiving-1-2-oral-anti-diabetic-drugs
#5
Michal Witkowski, Lars Wilkinson, Neil Webb, Alan Weids, Divina Glah, Hrvoje Vrazic
INTRODUCTION: Once-weekly semaglutide is a new glucagon-like peptide-1 (GLP-1) analogue administered at a 1.0 or 0.5 mg dose. As head-to-head trials assessing once-weekly semaglutide as an add-on to 1-2 oral anti-diabetic drugs (OADs) vs other GLP-1 receptor agonists (GLP-1 RAs) are limited, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of once-weekly semaglutide vs GLP-1 RAs in patients with type 2 diabetes (T2D) inadequately controlled on 1-2 OADs...
April 19, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29667023/liraglutide-effects-on-upper-gastrointestinal-investigations-implications-prior-to-bariatric-surgery
#6
Renuca Modi, Peter Rye, Sarah Cawsey, Daniel W Birch, Arya M Sharma
Liraglutide is a glucagon-like peptide type 1 (GLP-1) analogue that is approved for long-term obesity management in North America. While bariatric surgery remains the gold standard for weight loss, an increasing number of patients are on liraglutide in the setting of ongoing workup for bariatric surgery. The presence of gastrointestinal symptoms prior to bariatric surgery may prompt testing for dysmotility, which affects surgical decision making. Here we report six cases where treatment with liraglutide was associated with reversible reduction in gastric and esophageal motility in screening for bariatric surgery...
April 17, 2018: Obesity Surgery
https://www.readbyqxmd.com/read/29651202/a-narrative-review-of-potential-future-antidiabetic-drugs-should-we-expect-more
#7
REVIEW
Gaurav Chikara, Pramod Kumar Sharma, Pradeep Dwivedi, Jaykaran Charan, Sneha Ambwani, Surjit Singh
Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential...
April 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/29623579/pharmacokinetics-safety-and-tolerability-of-oral-semaglutide-in-subjects-with-renal-impairment
#8
Charlotte Granhall, Flemming L Søndergaard, Mette Thomsen, Thomas W Anderson
BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) as a tablet for oral administration. This trial (NCT02014259) investigated the pharmacokinetics, safety and tolerability of oral semaglutide in subjects with and without renal impairment. METHODS: Subjects were categorised as having normal renal function (n = 24), mild (n = 12), moderate (n = 12) or severe (n = 12) renal impairment, or end-stage renal disease (ESRD) requiring haemodialysis (n = 11) and received once-daily oral semaglutide (5 mg for 5 days followed by 10 mg for 5 days) in the fasting state, followed by 30 min fasting after dosing...
April 6, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29603687/mir-7-mir-9-and-mir-375-contribute-to-effect-of-exendin-4-on-pancreatic-%C3%AE-cells-in-high-fat-diet-fed-mice
#9
Chang Guo, Yi-Qiong Sun, Qiang Li, Jin-Chao Zhang
PURPOSE: The purpose of this study was to test whether glucagon-like peptide-1 (GLP-1) receptor activation preserved pancreatic β-cells via the regulation of microRNAs and target genes in high-fat-diet-fed mice. METHODS: C57BL/6 male mice were simultaneously treated with high-fat-diet (HFD) and GLP-1 analogue, Exendin-4 (Ex-4) (3 μg/kg/day or 30 μg/kg/day), i.p. or vehicle, for consecutive 13 weeks. Fasting blood glucose, postprandial blood glucose, ΔI30/ΔG30, HOMA-IR and HOMA-% β were measured in each group...
March 27, 2018: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/29603541/augmentation-of-glucagon-like-peptide-1-receptor-signalling-by-neprilysin-inhibition-potential-implications-for-patients-with-heart-failure
#10
REVIEW
Milton Packer
Augmentation of glucagon-like peptide-1 (GLP-1) receptor signalling is an established approach to the treatment of type 2 diabetes. However, endogenous GLP-1 and long-acting GLP-1 receptor analogues are degraded not only by dipeptidyl peptidase-4, but also by neprilysin. This observation raises the possibilities that endogenous GLP-1 contributes to the clinical effects of neprilysin inhibition and that patients concurrently treated with sacubitril/valsartan and incretin-based drugs may experience important drug-drug interactions...
March 30, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29574633/a-network-meta-analysis-comparing-semaglutide-once-weekly-with-other-glp-1-receptor-agonists-in-japanese-patients-with-type-2-diabetes
#11
Neil Webb, Michelle Orme, Michal Witkowski, Rie Nakanishi, Jakob Langer
INTRODUCTION: Semaglutide once-weekly (QW) is a novel glucagon-like peptide-1 (GLP-1) analogue administered at a 0.5 or 1.0 mg dose. In the absence of head-to-head trials between semaglutide QW and other GLP-1 receptor agonists (GLP-1 RAs) in a Japanese population, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of semaglutide QW vs GLP-1 RAs in Japanese patients with type 2 diabetes (T2DM), with a specific focus on the comparison between semaglutide 0...
March 24, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29549796/post-treatment-with-the-glp-1-analogue-liraglutide-alleviate-chronic-inflammation-and-mitochondrial-stress-induced-by-status-epilepticus
#12
Rui-Fang Wang, Guo-Fang Xue, Christian Hölscher, Miao-Jing Tian, Peng Feng, Ji-Ying Zheng, Dong-Fang Li
Glucagon-like peptide-1(GLP-1) is a growth factor that has neuroprotective and anti-inflammatory properties. The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease. Status epilepticus (SE) is a complex disorder, involving many underlying pathological processes, including excitotoxic and chronic inflammatory events. The present pilot study aims to investigate whether liraglutide alleviates the chronic inflammation response and mitochondrial stress induced by SE in the lithium-pilocarpine animal model...
May 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29547043/hypoglycemia-in-the-elderly-with-diabetes-a-growing-problem-with-emerging-solutions
#13
Martin M Grajower
Hypoglycemia is the major side effect of insulin therapy. The elderly are especially vulnerable to episodes of hypoglycemia, and with greater risks of complications such as falls. Two new long-acting basal insulins, glargine-300 (Gla-300) and degludec, are associated with lower incidences of hypoglycemia than previously available basal insulins. One of them, Gla-300, was studied in the elderly and has a lower incidence of hypoglycemia in patients over 65 years old. These new data should be incorporated into decision making when treating the elderly patient with insulin, whether they have type 1 or 2 diabetes...
March 2018: Endocrine Practice
https://www.readbyqxmd.com/read/29540315/novel-glp-1-glp-2-co-agonists-display-marked-effects-on-gut-volume-and-improves-glycemic-control-in-mice
#14
Pernille Wismann, Søren L Pedersen, Gitte Hansen, Karin Mannerstedt, Philip J Pedersen, Palle B Jeppesen, Niels Vrang, Keld Fosgerau, Jacob Jelsing
AIM: Analogues of several gastrointestinal peptide hormones have been developed into effective medicines for treatment of diseases such as type 2 diabetes mellitus (T2DM), obesity and short bowel syndrome (SBS). In this study, we aimed to explore whether the combination of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) into a potent co-agonist could provide additional benefits compared to existing monotherapies. METHODS: A short-acting (GUB09-123) and a half-life extended (GUB09-145) GLP-1/GLP-2 co-agonist were generated using solid-phase peptide synthesis and tested for effects on food intake, body weight, glucose homeostasis, and gut proliferation in lean mice and in diabetic db/db mice...
March 11, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29524296/liraglutide-a-human-glucagon-like-peptide-1-analogue-stimulates-akt-dependent-survival-signalling-and-inhibits-pancreatic-%C3%AE-cell-apoptosis
#15
Katerina Kapodistria, Effie-Photini Tsilibary, Eleni Kotsopoulou, Petros Moustardas, Paraskevi Kitsiou
Liraglutide, a human long-lasting GLP-1 analogue, is currently regarded as a powerful treatment option for type 2 diabetes. Apart from glucoregulatory and insulinotropic actions, liraglutide increases β-cell mass through stimulation of β-cell proliferation and islet neogenesis, as well as inhibition of β-cell apoptosis. However, the underline molecular mechanisms have not been fully characterized. In this study, we investigated the mechanism by which liraglutide preserves islet β-cells in an animal model of overt diabetes, the obese db/db mice, and protects a mouse pancreatic β-cell line (βTC-6 cells) against apoptosis...
March 10, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29516618/sodium-glucose-co-transporter-2-inhibitors-the-latest-residents-on-the-block-impact-on-glycaemic-control-at-a-general-practice-level-in-england
#16
Adrian H Heald, Anthony A Fryer, Simon G Anderson, Mark Livingston, Mark Lunt, Mark Davies, Gabriela Y C Moreno, Roger Gadsby, Robert J Young, Mike Stedman
AIMS: To determine, using published general practice-level data, how differences in Type 2 diabetes mellitus (T2DM) prescribing patterns relate to glycaemic target achievement levels. METHODS: Multiple linear regression modelling was used to link practice characteristics and defined daily dose (DDD) of different classes of medication in 2015/2016 and changes between that year and the year 2014/2015 in medication to proportion of patients achieving target glycaemic control (glycated haemoglobin A1c [HbA1c] ≤58 mmol/mol [7...
March 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29508275/eadsg-guidelines-insulin-therapy-in-diabetes
#17
Bahendeka Silver, Kaushik Ramaiya, Swai Babu Andrew, Otieno Fredrick, Sarita Bajaj, Sanjay Kalra, Bavuma M Charlotte, Karigire Claudine, Anthony Makhoba
A diagnosis of diabetes or hyperglycemia should be confirmed prior to ordering, dispensing, or administering insulin (A). Insulin is the primary treatment in all patients with type 1 diabetes mellitus (T1DM) (A). Typically, patients with T1DM will require initiation with multiple daily injections at the time of diagnosis. This is usually short-acting insulin or rapid-acting insulin analogue given 0 to 15 min before meals together with one or more daily separate injections of intermediate or long-acting insulin...
April 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29504049/future-pharmacotherapy-for-obesity-new-anti-obesity-drugs-on-the-horizon
#18
REVIEW
Gitanjali Srivastava, Caroline Apovian
PURPOSE OF REVIEW: Obesity is a global health crisis with detrimental effects on all organ systems leading to worsening disease state and rising costs of care. Persons with obesity failing lifestyle therapies need to be escalated to appropriate pharmacological treatment modalities, medical devices, and/or bariatric surgery if criteria are met and more aggressive intervention is needed. The progression of severe obesity in the patient population coupled with related co-morbidities necessitates the development of novel therapies for the treatment of obesity...
March 5, 2018: Current Obesity Reports
https://www.readbyqxmd.com/read/29503858/radiosynthesis-and-evaluation-of-an-18-f-labeled-silicon-containing-exendin-4-peptide-as-a-pet-probe-for-imaging-insulinoma
#19
Lukas O Dialer, Andreas Jodal, Roger Schibli, Simon M Ametamey, Martin Béhé
Background: Analogues of exendin-4 have been radiolabeled for imaging the glucagon-like peptide type 1 receptors (GLP-1R) which are overexpressed in insulinoma. The aim of this research was to synthesize an 18 F-labeled silicon containing exendin-4 peptide (18 F- 2 ) and to evaluate its in vitro and in vivo behavior in CHL-GLP-1 receptor positive tumor-bearing mice. 18 F-labeled silicon containing exendin-4 peptide (18 F- 2 ) was prepared via one-step nucleophilic substitution of a silane precursor with 18 F-fluoride in the presence of acetic acid and K222...
2018: EJNMMI Radiopharmacy and Chemistry
https://www.readbyqxmd.com/read/29475006/glutamine-up-regulates-pancreatic-sodium-dependent-neutral-aminoacid-transporter-2-and-mitigates-islets-apoptosis-in-diabetic-rats
#20
Zekrayat J H Medras, Norhan M El-Sayed, Sawsan A Zaitone, Eman A Toraih, Manal M Sami, Yasser M Moustafa
BACKGROUND: Glutamine aminoacid regulates insulin exocytosis from pancreatic β-cells. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has fascinated function in inhibiting β-cell apoptosis and preserving pancreatic β-cell mass. The present study investigated the benefit of adding glutamine to a regimen of liraglutide in diabetic rats focusing on their role in increasing insulin production and upregulation of the expression of sodium-dependent neutral aminoacid transporter-2 (SNAT2)...
April 2018: Pharmacological Reports: PR
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