GSE147693 Therapeutically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain
Contributor : Ho KoSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWith advances in single-cell genomics, molecular signatures of cells comprising the brain vasculature are revealed in unprecedented detail, yet the ageing-associated cell subtype transcriptomic changes which may contribute to neurovascular dysfunction in neurodegenerative diseases remain elusive. Here, we performed single-cell transcriptomic profiling of brain endothelial cells (EC) in young adult and aged mice to characterize their ageing-associated genome-wide expression changes. We identified zonation-dependent tran...
Source: GEO: Gene Expression Omnibus - March 30, 2020 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research

Efficacy and safety of generic exenatide injection in Chinese patients with type 2 diabetes: a multicenter, randomized, controlled, non-inferiority trial
This study aimed to compare the efficacy and safety of generic exenatide with branded exenatide Byetta® in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues.MethodsA multicenter, randomized, controlled, non-inferiority trial was performed. A total of 240 patients with T2DM and glycated hemoglobin (HbA1c)  ≥ 7% (53 mmol/mol) to ≤ 9.0% (75 mmol/mol) on monotherapy or combination therapy of metformin and insulin secretagogues for at least 3 months were randomized into ge...
Source: Acta Diabetologica - March 23, 2020 Category: Endocrinology Source Type: research

Efficacy and safety of meal-time administration of short-acting exenatide for glycaemic control in type 1 diabetes (MAG1C): a randomised, double-blind, placebo-controlled trial
Publication date: Available online 2 March 2020Source: The Lancet Diabetes & EndocrinologyAuthor(s): Nicklas J Johansen, Thomas F Dejgaard, Asger Lund, Camilla Schlüntz, Christian S Frandsen, Julie L Forman, Nicolai J Wewer Albrechtsen, Jens J Holst, Ulrik Pedersen-Bjergaard, Sten Madsbad, Tina Vilsbøll, Henrik U Andersen, Filip K Knop (Source: The Lancet Diabetes and Endocrinology)
Source: The Lancet Diabetes and Endocrinology - March 3, 2020 Category: Endocrinology Source Type: research

Triple Therapy with Exenatide/Pioglitazone/Metformin vs. Conventional Therapy: Changes in Liver Fibrosis Scores after 2 Years of Treatment in Patients with New-Onset Type 2 Diabetes Mellitus
Abstract (Source: Metabolism - Clinical and Experimental)
Source: Metabolism - Clinical and Experimental - March 1, 2020 Category: Biomedical Science Authors: Olga Lavrynenko, Muhammad Abdul-Ghani, Mariam Alatrach, Curtiss Puckett, John Adams, Naim Alkhouri, Ralph DeFronzo Source Type: research

Exploring the Possible Impact of Unbalanced Open-Label Drop-In of Glucose-Lowering Medications on EXSCEL Outcomes.
Conclusions: EXSCEL-observed HRs for MACE and ACM remained robust after right censoring or application of literature-derived risk reductions, but the exenatide versus placebo MACE effect size and statistical significance were increased by IPTW. Effects of open-label drop-in cardioprotective medications need to be considered carefully when designing, conducting, and analyzing cardiovascular outcome trials of glucose-lowering agents under the premise of glycemic equipoise. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01144338. PMID: 32098501 [PubMed - as supplied by publisher] (Source: Circulation)
Source: Circulation - February 26, 2020 Category: Cardiology Authors: Bethel MA, Stevens SR, Buse JB, Choi J, Gustavson SM, Iqbal N, Lokhnygina Y, Mentz RJ, Patel RA, Öhman P, Schernthaner G, Lecube A, Hernandez AF, Holman RR Tags: Circulation Source Type: research

Effectiveness of dulaglutide vs liraglutide and exenatide once-weekly. A real-world study and meta-analysis of observational studies
Real-word data on the head-to-head comparisons among glucagon-like peptide-1 receptor agonists (GLP-1RA) are scant. Therefore, we aimed to compare the effectiveness of dulaglutide versus liraglutide and exenatide once weekly (exeOW) in type 2 diabetic (T2D) patients under routine care. (Source: Metabolism - Clinical and Experimental)
Source: Metabolism - Clinical and Experimental - February 25, 2020 Category: Biomedical Science Authors: Mario Luca Morieri, Mauro Rigato, Vera Frison, Natalino Simioni, Michele D'Ambrosio, Federica Tadiotto, Agostino Paccagnella, Annunziata Lapolla, Angelo Avogaro, Gian Paolo Fadini Source Type: research

Ultra-sensitive bioanalysis of the therapeutic peptide exenatide for accurate pharmacokinetic analyses at effective plasma concentrations utilizing UPLC-MS/MS
Publication date: Available online 22 February 2020Source: Journal of Pharmaceutical AnalysisAuthor(s): Max Sauter, Philipp Uhl, Jürgen Burhenne, Walter E. HaefeliAbstractExenatide is the first approved glucagon-like peptide 1 receptor agonist subcutaneously or intramuscularly injected for the treatment of type 2 diabetes mellitus. Typical therapeutic plasma concentrations are in the low pg/mL range therefore requiring ultra-sensitive quantification. To enable the accurate evaluation of pharmacokinetic studies, we established a UPLC-MS/MS assay with a lower limit of quantification (LLOQ) of 5 pg/mL (1.2 pM) using 20...
Source: Journal of Pharmaceutical Analysis - February 23, 2020 Category: Drugs & Pharmacology Source Type: research

Metabolic measures 12 months after a randomised controlled trial of treatment of clozapine associated obesity and diabetes with exenatide (CODEX)
We examined whether this effect was maintained at 12-months post-intervention. We followed up CODEX trial participants at 12-months post trial endpoint, collecting information on weight, BMI, waist circumference, blood pressure, fasting glucose, HbA1c, and use of metformin. The primary outcome of interest was change in weight from trial baseline to 12-months post endpoint and trial endpoint to 12-months post endpoint compared between former exenatide and usual care participants. Only HbA1c differed between baseline and 12-months post endpoint between the exenatide and control groups. From endpoint to 12-month follow up the...
Source: Journal of Psychiatric Research - February 19, 2020 Category: Psychiatry Source Type: research

A 6 ‐month randomized, double‐blind, placebo‐controlled trial of weekly exenatide in adolescents with obesity
SummaryBackgroundPharmacological treatment options for adolescents with obesity are very limited. Glucagon ‐like‐peptide‐1 (GLP‐1) receptor agonist could be a treatment option for adolescent obesity.ObjectiveTo investigate the effect of exenatide extended release on body mass index (BMI) ‐SDS as primary outcome, and glucose metabolism, cardiometabolic risk factors, liver steatosis, and other BMI metrics as secondary outcomes, and its safety and tolerability in adolescents with obesity.MethodsSix ‐month, randomized, double‐blinded, parallel, placebo‐controlled clinical trial in patients (n = 44, 10‐18&thin...
Source: Pediatric Obesity - February 17, 2020 Category: Eating Disorders & Weight Management Authors: D. Weghuber, A. Forslund, H. Ahlstr öm, A. Alderborn, K. Bergström, S. Brunner, J. Cadamuro, I. Ciba, M. Dahlbom, V. Heu, J. Hofmann, H. Kristinsson, J. Kullberg, A. Ladinger, F. B. Lagler, M. Lidström, H. Manell, M. Meirik, K. Mörwa Tags: ORIGINAL RESEARCH Source Type: research

A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release, Dulaglutide and Liraglutide in the UK
AbstractIntroductionOnce-weekly semaglutide 1  mg is a novel glucagon-like peptide 1 receptor agonist (GLP-1 RA) that, in the SUSTAIN clinical trials, has demonstrated greater reductions in glycated haemoglobin (HbA1c) and body weight than the other GLP-1 RAs exenatide extended-release (ER) 2 mg, dulaglutide 1.5 mg and liraglutide 1.2 mg. The aim of this analysis was to evaluate the relative cost of control of achieving treatment goals in people with type 2 diabetes (T2D) treated with once-weekly semaglutide versus exenatide ER, dulaglutide and liraglutide from a UK perspective.MethodsProporti...
Source: Advances in Therapy - February 11, 2020 Category: Drugs & Pharmacology Source Type: research

Safety, Tolerability and Pharmacokinetics of Single Dose Polyethylene Glycolated Exenatide Injection (PB-119) in Healthy Volunteers
ConclusionThe administration of polyethylene glycolated exenatide injection at a single dose of 2 –200 µg is safe and tolerable for healthy volunteers. Once-weekly polyethylene glycolated exenatide injection can be recommended.Clinical Trials RegistrationThe study was registered at clinicaltrials.gov (No. NCT02084251). (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - January 31, 2020 Category: Drugs & Pharmacology Source Type: research

Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map
We examined the association between glucose-lowering medications and a broad range of cardiovascular outcomes, and assessed the strength of evidence for these associations.MethodsFor this umbrella review we searched PubMed, Embase, and the Cochrane Library to identify systematic reviews and meta-analyses of randomised controlled trials examining the cardiovascular safety of glucose-lowering medications. Cardiovascular outcomes examined included major adverse cardiovascular events, cardiovascular death, myocardial infarction, stroke, heart failure, unstable angina, and atrial fibrillation. For each meta-analysis, we estimat...
Source: The Lancet Diabetes and Endocrinology - January 30, 2020 Category: Endocrinology Source Type: research

Oral semaglutide versus injectable glucagon-like peptide-1 receptor agonists: A cost of control analysis.
Authors: B Hansen B, Nuhoho S, Ali SN, Dang-Tan T, Valentine WJ, Malkin S, Hunt B Abstract Aims: The efficacy and safety of oral semaglutide, the first glucagon-like peptide-1 (GLP-1) receptor agonist developed for oral administration for the treatment of type 2 diabetes, was evaluated in the PIONEER clinical trial program, and a recently published network meta-analysis allowed comparison with further injectable GLP-1 receptor agonists. The present study aimed to assess the short-term cost effectiveness of oral semaglutide 14 mg versus subcutaneous once-weekly dulaglutide 1.5 mg, once-weekly exenatide...
Source: Journal of Medical Economics - January 29, 2020 Category: Health Management Tags: J Med Econ Source Type: research

Twelve weeks of exenatide treatment increases [18F]fluorodeoxyglucose uptake by brown adipose tissue without affecting oxidative resting energy expenditure in nondiabetic males
Brown adipose tissue (BAT) improves energy metabolism by combusting glucose and lipids into heat. Agonism of the glucagon-like peptide-1 receptor (GLP-1R) within the central nervous system activates BAT in mice. Moreover, in patients with type 2 diabetes, GLP-1R agonism lowers body weight and improves glucose and lipid levels, possibly involving BAT activation. Interestingly, people from South Asian descent are prone to develop cardiometabolic disease. We studied the effect of GLP-1R agonism on BAT in humans, specifically in South Asians and Europids without obesity or type 2 diabetes. (Source: Metabolism - Clinical and Experimental)
Source: Metabolism - Clinical and Experimental - January 23, 2020 Category: Biomedical Science Authors: Laura G.M. Janssen, Kimberly J. Nahon, Katrien F.M. Brack é, Dennis van den Broek, Renée Smit, Aashley S.D. Sardjoe Mishre, Lisa L. Koorneef, Borja Martinez-Tellez, Jedrzej Burakiewicz, Hermien E. Kan, Floris H.P. van Velden, Lenka M. Pereira Arias-Boud Source Type: research

The Route from the Folded to the Amyloid State: Exploring the Potential Energy Surface of a Drug-Like Miniprotein.
wara T, Perczel A Abstract Invited for the cover of this issue is the group of András Perczel at Eötvös Loránd University, Budapest, Hungary and colleagues from Osaka University, Japan. The image depicts the amyloid buildup of an Exenatide derivate miniprotein (E5) monitored on a simplified hyperspace. Read the full text of the article at 10.1002/chem.201903826. PMID: 31961031 [PubMed - as supplied by publisher] (Source: Chemistry)
Source: Chemistry - January 21, 2020 Category: Chemistry Authors: Taricska N, Horváth D, Menyhárd DK, Ákontz-Kiss H, Noji M, So M, Goto Y, Fujiwara T, Perczel A Tags: Chemistry Source Type: research

Short-term GLP-1 receptor agonist exenatide ameliorates intramyocellular lipid deposition without weight loss in ob/ob mice
International Journal of Obesity, Published online: 07 January 2020; doi:10.1038/s41366-019-0513-yShort-term GLP-1 receptor agonist exenatide ameliorates intramyocellular lipid deposition without weight loss in ob/ob mice (Source: International Journal of Obesity)
Source: International Journal of Obesity - January 7, 2020 Category: Eating Disorders & Weight Management Authors: Fen Xu Huanyi Cao Zonglan Chen Huimin Gu Wanrong Guo Beisi Lin Jianping Weng Source Type: research

Does evidence matter? Comparative effectiveness research and prescribing of Type 2 diabetes mellitus drugs.
Conclusion: CER evidence appeared to be associated with prescribing trends in GLP-1 agonists market; however, no associations were found in DPP4 inhibitors market. The translation of evidence into practice can be limited by the availability of superiority trials and timing of their availability. PMID: 31789054 [PubMed - as supplied by publisher] (Source: Journal of Comparative Effectiveness Research)
Source: Journal of Comparative Effectiveness Research - December 5, 2019 Category: General Medicine Tags: J Comp Eff Res Source Type: research

Therapeutic efficacy of arginine-rich exenatide on diabetic neuropathy in rats.
Abstract Diabetes mellitus is characterized by metabolic dysregulation associated with a number of health complications. More than 50% of patients with diabetes mellitus suffer from diabetic polyneuropathy, which involves the presence of peripheral nerve dysfunction symptoms. The aim of this study was to evaluate the potential of a new synthetic arginine-rich exendin-4 (Peptide D) in the treatment of complications caused by diabetes, including peripheral neuropathy, in rats. Diabetes was induced by administering streptozotocin (STZ). Three groups of diabetic rats were treated with Peptide D (0.1, 1, and 10 μg...
Source: European Journal of Pharmacology - November 30, 2019 Category: Drugs & Pharmacology Authors: Shekunova EV, Kashkin VA, Muzhikyan AА, Makarova MN, Makarov VG, Balabanyan VY Tags: Eur J Pharmacol Source Type: research

Diabetes drugs for nonalcoholic fatty liver disease: a systematic review
ConclusionsConsistent with existing clinical practice guidelines, which recommend lifestyle intervention and treatment for comorbidities related to fatty liver disease as first-line treatment, trial evidence supports the efficacy of some diabetes drugs (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with some diabetes drugs may warrant caution. Larger trials are needed to better characterize the efficacy and harms of diabetes pharmacotherapy in these patients. (Source: Systematic Reviews)
Source: Systematic Reviews - November 29, 2019 Category: International Medicine & Public Health Source Type: research

Alcohol-mediated behaviours and the gut-brain axis; with focus on glucagon-like peptide-1.
Abstract The neurochemical mechanisms that regulate development of alcohol use disorder (AUD) are complex, and gut-brain peptides were recently pinpointed as novel modulators. Gut-brain peptides, such as glucagon-like peptide-1 (GLP-1), are well known for their ability to regulate food intake and appetite. GLP-1 also controls glucose homeostasis, which lead to the approval of GLP-1 receptor agonists for treatment of diabetes type II. These pharmacotherapies, including exenatide/exendin-4(Ex4) and liraglutide, have also been tested in various animal modes of AUD. In mice, Ex4 attenuates the acute behavioural respon...
Source: Brain Research - November 21, 2019 Category: Neurology Authors: Elisabet J Tags: Brain Res Source Type: research

Sustainable, cost-efficient manufacturing of therapeutic peptides using chemo-enzymatic peptide synthesis (CEPS)
Green Chem., 2019, Accepted Manuscript DOI: 10.1039/C9GC03600H, PaperJan Pawlas, Timo Nuijens, Jonas Persson, Thomas Svensson, Marcel Schmidt, Ana Toplak, Mikael Nilsson, Jon Holbech Rasmussen Using a large scale biocatalytic manufacture of the antidiabetic exenatide as an example we report that chemo-enzymatic peptide synthesis (CEPS) constitutes an efficient method for sustainable manufacturing of therapeutic peptides.... The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Green Chem. latest articles)
Source: RSC - Green Chem. latest articles - November 7, 2019 Category: Chemistry Authors: Jan Pawlas Source Type: research

Simultaneous angiotensin receptor blockade and glucagon-like peptide-1 receptor activation ameliorate albuminuria in obese insulin-resistant rats.
Abstract Insulin resistance increases renal oxidant production by up-regulating NADPH oxidase 4 (Nox4) expression contributing to oxidative damage and ultimately albuminuria. Inhibition of the renin-angiotensin system (RAS) and activation of glucagon-like peptide-1 (GLP-1) receptor signaling may reverse this effect. However, whether angiotensin receptor type 1 (AT1) blockade and GLP-1 receptor activation improve oxidative damage and albuminuria through different mechanisms is not known. Using insulin resistant Otsuka Long Evan Tokushima Fatty (OLETF) rats, we tested the hypothesis that simultaneous blockade of AT1...
Source: Clinical and Experimental Pharmacology and Physiology - November 1, 2019 Category: Drugs & Pharmacology Authors: Rodriguez R, Escobedo B, Lee AY, Thorwald M, Godoy-Lugo JA, Nakano D, Nishiyama A, Parkes DG, Ortiz RM Tags: Clin Exp Pharmacol Physiol Source Type: research

Glucagon-like peptide-1 receptor agonist exendin-4 mitigates lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages.
Abstract Macrophages play a critical role in the immune response against pathogen invasion and injury. However, under pathological stress, macrophages could have aberrant roles and contribute to the pathogenesis of inflammatory associated diseases. Exenatide is a glucagon-like peptide 1(GLP-1) agonist, which belongs to the family of synthetic exendin-based incretin mimetic. Exendin related compounds reduce glucose levels in type 2 diabetes patients. The purpose of this study was to examine the anti-inflammatory effects of exendin-4 in LPS-induced activation of macrophages. We show that exendin-4 inhibits LPS-induc...
Source: International Immunopharmacology - November 1, 2019 Category: Allergy & Immunology Authors: Lu C, Xie T, Guo X, Wu D, Li S, Li X, Lu Y, Wang X Tags: Int Immunopharmacol Source Type: research

Assessment of real ‐time and quantitative changes in renal hemodynamics in healthy overweight males: Contrast‐enhanced ultrasonography vs para‐aminohippuric acid clearance
ConclusionsContrast ‐enhanced ultrasonography can detect acute drug‐induced changes human renal hemodynamics. CEUS‐assessed renal cortical microvascular blood flow moderately associates with effective renal plasma flow, particularly when perfusion is in normal‐to‐high range. Renal CEUS cannot replace effectiv e renal plasma flow measurements, but may be a complementary tool to characterize regional kidney perfusion. (Source: Microcirculation)
Source: Microcirculation - October 28, 2019 Category: Research Authors: Marcel H. A. Muskiet, Anna L. Emanuel, Mark M. Smits, Lennart Tonneijck, Rick I. Meijer, Jaap A. Joles, Erik H. Sern é, Daniël H. van Raalte Tags: ORIGINAL ARTICLE Source Type: research

Mechanism of the neuroprotective effect of GLP-1 in a rat model of Parkinson's with pre-existing diabetes
ConclusionsDiabetes increases the severity of impairment in PD, and GLP-1 improve it through its direct neuronal effect in addition to its indirect effect through producing hypoglycemia.Graphical abstract (Source: Neurochemistry International)
Source: Neurochemistry International - October 24, 2019 Category: Neuroscience Source Type: research

The route from the folded to the amyloid state: exploring the potential energy surface of a drug-like miniprotein.
wara T, Perczel A Abstract The amyloid formation of the folded segment of a variant of Exenatide (a marketed drug for Type-2 Diabetes Mellitus ) was studied by ECD and NMR. We found that the optimum temperature for E5 protein amyloidosis coincides with body temperature and requires well below physiological salt concentration. Decomposition of the ECD spectra and its barycentric representation on the folded-unfolded-amyloid potential energy surface allowed us to monitor the full range of molecular transformation of amyloidogenesis. We identified points of no return ( e.g. T =37°C, pH =4.1, c E5 =250µM, c ...
Source: Chemistry - October 24, 2019 Category: Chemistry Authors: Taricska N, Horváth D, Menyhárd D, Ákontz-Kiss H, Noji M, So M, Goto Y, Fujiwara T, Perczel A Tags: Chemistry Source Type: research

Effects of exenatide and open-label SGLT2 inhibitor treatment, given in parallel or sequentially, on mortality and cardiovascular and renal outcomes in type 2 diabetes: insights from the EXSCEL trial
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve cardiovascular and renal outcomes in patients with type 2 diabetes through distinct mechanism... (Source: Cardiovascular Diabetology)
Source: Cardiovascular Diabetology - October 22, 2019 Category: Cardiology Authors: Lindsay E. Clegg, Robert C. Penland, Srinivas Bachina, David W. Boulton, Marcus Thuresson, Hiddo J. L. Heerspink, Stephanie Gustavson, C. David Sj öström, James A. Ruggles, Adrian F. Hernandez, John B. Buse, Robert J. Mentz and Rury R. Holman Tags: Original investigation Source Type: research

Glucagon-like peptide 1 receptor agonists in type 1 diabetes mellitus.
CONCLUSION: GLP-1 RA therapy represents an important add-on therapy option for achieving decreased insulin doses, weight loss, and modest improvements in HbA1c levels without significantly increasing hypoglycemia risk in patients with T1DM. Patients who have detectable C-peptide and/or are overweight or cannot achieve glycemic goals without hypoglycemia have been found to benefit the most from GLP-1 RA therapy. Further studies are warranted to evaluate these agents' potential impact on clinical outcomes such as microvascular and macrovascular complications. PMID: 31612934 [PubMed - in process] (Source: American Journa...
Source: American Journal of Health-System Pharmacy : AJHP - October 15, 2019 Category: Drugs & Pharmacology Authors: Guyton J, Jeon M, Brooks A Tags: Am J Health Syst Pharm Source Type: research

Efficacy and safety of once ‐weekly exenatide after switching from twice‐daily exenatide in patients with type 2 diabetes
In the present study, we report the efficacy and safety of once ‐weekly extended‐release exenatide after switching from twice‐daily exenatide in Japanese patients with type 2 diabetes. AbstractAims/IntroductionTo evaluate the efficacy and safety of once ‐weekly (q.w.) extended‐release exenatide after switching from twice‐daily (b.i.d.) exenatide in patients with type 2 diabetes.Materials and MethodsThis was an investigator ‐initiated, prospective, single‐arm, multicenter study. Individuals with type 2 diabetes who had been treated with exenatide b.i.d. for at least 3 months were enrolled...
Source: Journal of Diabetes Investigation - October 8, 2019 Category: Endocrinology Authors: Yuusuke Watanabe, Yoshifumi Saisho, Jun Inaishi, Kinsei Kou, Akira Yamauchi, Yasuhiko Kanazawa, Yoshiaki Okubo, Mikiya Tokui, Takatoshi Imai, Rie Murakami, Tami Tsuchiya, Hironobu Sasaki, Tatsuhiro Masaoka, Junichiro Irie, Shu Meguro, Hiros Tags: Clinical Trial Source Type: research

Mono-PEGylates of Exenatide in Branched and Dimeric Structures Can Improve In vivo Stability and Hypoglycemic Bioactivity
In this study, we attempted residue-specific mono-PEGylation to the middle of the amino acid backbone to extend its in vivo half-life. Exenatide was point-mutated from Lys to Cys at the 12th residue to yield a variant (K12C), and PEG-maleimide of varying molecular weights (MW) (5, 10, 20, 40 kD) was site-specifically conjugated to yield a mono-PEGylate with branched T-shape molecular structure. In another approach, we conjugated a bis-maleimide PEG (10 kD) to the middle of two K12Cs to yield an H-shape homodimer PEGylate In vitro bioactivity assays indicated that: (1) PEGylates conjugated with higher MW PEG l...
Source: Journal of Biotechnology - October 1, 2019 Category: Biotechnology Source Type: research

Oral Semaglutide (Rybelsus) for Type 2 Diabetes
Date: October 21, 2019 Issue #:  1583Summary:  An oral formulation of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Rybelsus– Novo Nordisk) has been approved by the FDA for once-daily treatment of type 2 diabetes in adults. Semaglutide, which has been available in a subcutaneously-injected formulation(Ozempic) since 2017, is the first GLP-1 receptor agonist to become available for oral administration; the 4 other GLP-1 receptor agonists currently available in the US are administered by subcutaneous (SC) injection. (Source: The Medical Letter)
Source: The Medical Letter - September 27, 2019 Category: Drugs & Pharmacology Authors: admin Tags: Adlyxine Bydureon Byetta dulaglutide Exenatide Glucophage Liraglutide lixisenatide Metformin Ozempic Rybelsus semaglutide Trulicity type 2 diabetes Source Type: research

Effect of Once-Weekly Exenatide in Patients With Type 2 Diabetes With and Without Heart Failure and Heart Failure-Related Outcomes: Insights From the EXSCEL Trial.
Conclusions: In EXSCEL, the use of EQW in patients with or without HF was well tolerated, but benefits of EQW on reduction in all-cause death and first hospitalization for HF were attenuated in patients with baseline HF. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01144338. PMID: 31542942 [PubMed - as supplied by publisher] (Source: Circulation)
Source: Circulation - September 23, 2019 Category: Cardiology Authors: Fudim M, White J, Pagidipati NJ, Lokhnygina Y, Wainstein J, Murin J, Iqbal N, Öhman P, Lopes RD, Reicher B, Holman RR, Hernandez AF, Mentz RJ Tags: Circulation Source Type: research

Unexpected bleeding after Exenatide treatment: a causative relationship or a coincidence?
CONCLUSIONS: To the best of our knowledge, this is the first report of spontaneous bleeding probably caused by Exenatide. The exact pathophysiology, by which the drug can cause spontaneous bleeding, is still not clear and has to be revealed. PMID: 31517602 [PubMed - in process] (Source: Endocrine Regulations)
Source: Endocrine Regulations - September 15, 2019 Category: Endocrinology Tags: Endocr Regul Source Type: research

A pilot study of exenatide actions in Alzheimer's disease.
CONCLUSION: The positive finding of lower EV Aβ42 supports emerging evidence that plasma neuronal EVs provide an effective platform for demonstrating biomarker responses in clinical trials in AD. The study was underpowered due to early termination and therefore we cannot draw any firm conclusions. However, the analysis of secondary outcomes shows no trends in support of the hypothesis that exenatide is disease- modifying in clinical AD, and lowering EV Aβ42 in and of itself may not improve cognitive outcomes in AD. PMID: 31518224 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research)
Source: Current Alzheimer Research - September 13, 2019 Category: Neurology Authors: Mullins RJ, Mustapic M, Chia CW, Carlson O, Gulyani S, Tran J, Li Y, Mattson MP, Resnick S, Egan JM, Greig NH, Kapogiannis D Tags: Curr Alzheimer Res Source Type: research

Efficacy and safety of once ‐weekly exenatide after switching from twice‐daily exenatide in patients with type 2 diabetes
AbstractAimsTo evaluate the efficacy and safety of once ‐weekly (QW) extended‐release exenatide after switching from twice‐daily (BID) exenatide in patients with type 2 diabetes (T2DM).MethodsThis was an investigator ‐initiated, prospective, single‐arm, multicenter study. Subjects with T2DM who had been treated with exenatide BID for at least 3 months were enrolled and switched to exenatide QW for 24 weeks. The primary endpoint was change in HbA1c at week 24, to test the glucose‐lowering effect of exenatid e QW versus exenatide BID.ResultsFifty ‐eight Japanese subjects with T2DM completed the study. HbA1c was...
Source: Journal of Diabetes Investigation - September 13, 2019 Category: Endocrinology Authors: Yuusuke Watanabe, Yoshifumi Saisho, Jun Inaishi, Kinsei Kou, Akira Yamauchi, Yasuhiko Kanazawa, Yoshiaki Okubo, Mikiya Tokui, Takatoshi Imai, Rie Murakami, Tami Tsuchiya, Hironobu Sasaki, Tatsuhiro Masaoka, Junichiro Irie, Shu Meguro, Hiros Tags: CLINICAL TRIAL Source Type: research

Effects of obesity induced by high-calorie diet and its treatment with exenatide on muscarinic acetylcholine receptors in rat hippocampus.
Abstract Here, we described the effects of obesity induced by high-calorie diet and its treatment with exenatide, an anti-diabetogenic and potential anti-obesogenic drug derived from the venom of the Gila monster Heloderma suspectum, on the affinity, density, subtypes and intracellular signaling pathways linked to activation of muscarinic acetylcholine receptors (mAChRs) in rat hippocampus. Male Wistar rats were divided into three groups: control (CT), obese induced by high-calorie diet (DIO) and DIO treated with exenatide (DIO+E). [3H]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium d...
Source: Biochemical Pharmacology - September 3, 2019 Category: Drugs & Pharmacology Authors: Silva MFP, Alves PL, Alponti RF, Silveira PF, Abdalla FMF Tags: Biochem Pharmacol Source Type: research

Proteins' fold compactness alters disulfide-bond reducibility by 3 orders of magnitude: a comprehensive kinetic case study on reduction of different size Trp-cage model proteins.
Abstract We derived a novel approach to monitor disulfide bond reduction in the vicinity of aromatic cluster(s) by using the near-UV range (266-293 nm) of ECD spectra. By using combined NMR- and ECD-spectroscopy we have determined the 3D-fold characteristics and the associated reduction rate constants (k) of E19_SS - a highly thermostable; disulfide bond reinforced 39-amino acid long Exenatide mimetic - and its N-terminally truncated derivatives at different experimental conditions. Single SS-bond reduction of the E19_SS model (using 18-fold excess of TCEP, pH = 7, 37 °C) takes hours, 20-30 times longer than e...
Source: Chembiochem - September 2, 2019 Category: Biochemistry Authors: Horvath D, Taricska N, Keszei E, Straner P, Farkas V, Toth GK, Perczel A Tags: Chembiochem Source Type: research

Dipeptidyl peptidase-4 inhibitors do not alter GH/IGF-I axis in adult diabetic patients
AbstractPurposeIncretin-based therapies have been introduced in clinical practice for type 2 diabetes mellitus (T2DM) treatment in the last few years. Current available medications of this class include glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. In addition to GLP-1, DPP-4 is able to inactivate  many others peptides as hypothalamic growth hormone-releasing hormone (GHRH). The aim of this exploratory study was to evaluate, on adult diabetic patients, the impact of therapy with incretins, particularly DPP-4 inhibitors on GH/IGF-I axis.Methods60 patients with T2D...
Source: Journal of Endocrinological Investigation - August 31, 2019 Category: Endocrinology Source Type: research

Novel lipid side chain modified exenatide analogs emerged prolonged glucoregulatory activity and potential body weight management properties.
Abstract Exenatide is known as the first marketed GLP-1 agonist for antidiabetic treatment, but it need twice injection a day because of its fast clearance. This work aims to prolong the half-life of exenatide by modified with novel lipid chain. Four optimized exenatide analogs named as Cys12-Exenatide (1-39)-NH2, Cys40-Exenatide (1-39)-NH2, Cys12-Tyr22-Gln24-Glu28-Arg35-Exenatide (1-39)-NH2 and Tyr22-Gln24-Glu28-Arg35-Cys40-Exenatide (1-39)-NH2 were selected and applied for conjugation. Then a series of evaluations including GLP-1R activation assay were conducted, conjugation C2 was selected for further investiga...
Source: Bioorganic and Medicinal Chemistry - August 23, 2019 Category: Chemistry Authors: Li C, Cai X, Dai Y, Liu C, Bi X, Zhou J, Li Q, Sun L, Huang W, Hou Z, Qian H Tags: Bioorg Med Chem Source Type: research

Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials
Publication date: Available online 14 August 2019Source: The Lancet Diabetes & EndocrinologyAuthor(s): Søren L Kristensen, Rasmus Rørth, Pardeep S Jhund, Kieran F Docherty, Naveed Sattar, David Preiss, Lars Køber, Mark C Petrie, John J V McMurraySummaryBackgroundGlucagon-like peptide-1 (GLP-1) receptor agonists differ in their structure and duration of action and have been studied in trials of varying sizes and with different patient populations, with inconsistent effects on cardiovascular outcomes reported. We aimed to synthesise the available evidence by doing a systematic review and meta-analysi...
Source: The Lancet Diabetes and Endocrinology - August 15, 2019 Category: Endocrinology Source Type: research

DPP-4 inhibition by linagliptin prevents cardiac dysfunction and inflammation by targeting the Nlrp3/ASC inflammasome
AbstractWe compared the effects of linagliptin (Lina, a DPP4 inhibitor) and GLP-1 receptor activation by exenatide followed by exendin-4 in an infusion pump (EX) on infarct size (IS), post-infarction activation of the inflammasome and remodeling in wild-type (WT) and db/db diabetic mice. Mice underwent 30  min ischemia followed by 24 h reperfusion. IS was assessed by TTC. Additional mice underwent permanent coronary artery occlusion. Echocardiography was performed 2w after infarction. Activation of the inflammasome in the border zone of the infarction was assessed by rt-PCR and ELISA 2w after reper fusion. Furthe...
Source: Basic Research in Cardiology - August 6, 2019 Category: Cardiology Source Type: research

Locally delivered GLP-1 analogues liraglutide and exenatide enhance microvascular perfusion in individuals with and without type 2 diabetes
AbstractAims/hypothesisGlucagon-like peptide-1 (GLP-1) analogues reduce the risk of macrovascular disease in diabetes; however, little is known about their microvascular effects. This research examined the microvascular actions of the GLP-1 analogues liraglutide and exenatide in individuals with and without type 2 diabetes (study 1). It also explored the involvement of the GLP-1 receptor (study 2) and the nitric oxide pathway in mediating the microvascular effects of the analogues.MethodsTrial design: Studies 1 and 2 had a randomised, controlled, double-blind study design. Study 1 participants, intervention and methods: th...
Source: Diabetologia - August 2, 2019 Category: Endocrinology Source Type: research

Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Their Use and Differential Features
AbstractGlucagon-like peptide-1 receptor agonists (GLP-1RAs) are well established as effective adjuncts to lifestyle modification in the treatment of type 2 diabetes (T2D) as monotherapy or in combination with oral glucose-lowering drugs  ± insulin. The six subcutaneous GLP-1RA formulations (i.e. twice-daily exenatide, once-daily liraglutide and lixisenatide, and once-weekly dulaglutide, exenatide and semaglutide) currently available in the EU and USA have many similarities, but also some unique features and properties. By stim ulating GLP-1 receptors, GLP-1RAs increase insulin secretion and suppress g...
Source: Clinical Drug Investigation - August 1, 2019 Category: Drugs & Pharmacology Source Type: research

Glucagon-Like Peptide-1 Receptor Analogues in Type 2 Diabetes: Their Use and Differential Features
AbstractGlucagon-like peptide-1 receptor analogues/agonists (GLP-1RAs) are well established as effective adjuncts to lifestyle modification in the treatment of type 2 diabetes (T2D) as monotherapy or in combination with oral glucose-lowering drugs  ± insulin. The six subcutaneous GLP-1RA formulations (i.e. twice-daily exenatide, once-daily liraglutide and lixisenatide, and once-weekly dulaglutide, exenatide and semaglutide) currently available in the EU and USA have many similarities, but also some unique features and properties. By stim ulating GLP-1 receptors, GLP-1RAs increase insulin secretion and ...
Source: Clinical Drug Investigation - July 18, 2019 Category: Drugs & Pharmacology Source Type: research

Assessment of real ‐time and quantitative changes in renal hemodynamics in healthy overweight males: contrast‐enhanced ultrasonography versus para‐aminohippuric acid clearance
ConclusionsCEUS can detect acute drug ‐induced changes human renal hemodynamics. CEUS‐assessed RCMBF moderately associates with ERPF, particularly when perfusion is in normal‐to‐high range. CEUS cannot replace ERPF‐measurements, but may be a complementary tool to characterize regional kidney‐perfusion.This article is protected by copyright. All rights reserved. (Source: Microcirculation)
Source: Microcirculation - July 17, 2019 Category: Research Authors: Marcel H.A. Muskiet, Anna L. Emanuel, Mark M. Smits, Lennart Tonneijck, Rick I. Meijer, Jaap A. Joles, Erik H. Sern é, Daniel van Raalte Tags: ORIGINAL RESEARCH Source Type: research

Correction to: Management of Patients with Type 2 Diabetes with Once-Weekly Semaglutide Versus Dulaglutide, Exenatide ER, Liraglutide and Lixisenatide: A Cost-Effectiveness Analysis in the Danish Setting
In the original publication, Figs.  3 and 5 and the final sentence in the final paragraph of Results/Sensitivity Analyses were incorrectly published. The corrected statement and the figures are given below. (Source: Diabetes Therapy)
Source: Diabetes Therapy - July 6, 2019 Category: Endocrinology Source Type: research

In-vivo Half-Life and Hypoglycemic Bioactivity of a Fusion Protein of Exenatide and Elastin-Based Polypeptide from Recombinant Saccharomyces cerevisiae
In this study, to further extend its in vivo half-life, we constructed a fusion protein (Ex-(EBP)10-6xHis) using a biocompatible and inert elastin-based polypeptide (EBP) as a fusion partner. Valine was inserted into the guest position of the pentapeptide (VPGXG), no linker sequence was inserted in between the EBPs, and (EBP)10-6xHis tag was attached to the C-terminus of exenatide. By using a recombinant Saccharomyces cerevisiae expression system, the fusion protein was expressed and secreted to the broth and purified by Ni-NTA affinity chromatography. Compared with the native exenatide, the physical half-life of the fusio...
Source: Journal of Biotechnology - July 4, 2019 Category: Biotechnology Source Type: research

Protective effects of glucagon ‐like peptide‐1 on cardiac remodeling by inhibiting oxidative stress through mammalian target of rapamycin complex 1/p70 ribosomal protein S6 kinase pathway in diabetes mellitus
ConclusionsGlucagon ‐like peptide‐1 protects the cardiomyocytes from oxidative stress and apoptosis in diabetes mellitus, which might contribute to the improvement of cardiac remodeling. The cardiac protection of GLP‐1 might be dependent on inhibition of mammalian target of rapamycin complex 1/p70 ribosomal prot ein S6 kinase, through an adenosine monophosphate‐activated protein kinase‐mediated pathway. (Source: Journal of Diabetes Investigation)
Source: Journal of Diabetes Investigation - July 2, 2019 Category: Endocrinology Authors: Dongjuan Wang, Longfu Jiang, Beili Feng, Nana He, Yue Zhang, Honghua Ye Tags: Original Article Source Type: research

Potential effectiveness of exenatide in experimentally-induced osteoporosis
ConclusionExenatide has a potential prophylactic and therapeutic role in the management postmenopausal osteoporosis. The non-inferiority of exenatide to vitamin D in treatment of osteoporosis is deduced. (Source: The Egyptian Rheumatologist)
Source: The Egyptian Rheumatologist - June 15, 2019 Category: Rheumatology Source Type: research

The protective effects of glucagon ‐like peptide‐1 on cardiac remodeling by inhibiting oxidative stress through mammalian target of rapamycin complex 1 /p70 ribosomal protein S6 kinase pathway in diabetes mellitus
ConclusionsGLP ‐1 protects the cardiomyocyte from oxidative stress and apoptosis in DM, which may contribute to the improvement of cardiac remodeling. The cardiac protection of GLP‐1 may be dependent on inhibition of mTORC1/p70S6K, via an AMPK‐mediated pathway.This article is protected by copyright. All rights reserved. (Source: Journal of Diabetes Investigation)
Source: Journal of Diabetes Investigation - June 14, 2019 Category: Endocrinology Authors: Dongjuan Wang, Longfu Jiang, Beili Feng, Nana He, Yue Zhang, Honghua Ye Tags: Original Article Source Type: research