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https://www.readbyqxmd.com/read/29799205/a-lithocholic-acid-based-peptide-delivery-system-for-enhanced-pharmacological-and-pharmacokinetic-profile-of-xenopus-glp-1-analogs
#1
Jing Han, Xinyu Chen, Li-Ming Zhao, Junjie Fu, Lidan Sun, Ying Zhang, Feng Zhou, Yingying Fei
GLP-1 analogs suffer from the main disadvantage of a short in vivo half-life. Lithocholic acid (LCA), one of the four main bile acids in human body, possesses a high albumin binding rate. We therefore envisioned that a LCA-based peptide delivery system could extend the half-life of GLP-1 analogs by facilitating the noncovalent binding of peptides to human serum albumin. Based on our previously identified Xenopus GLP-1 analogs (1-3), a series of LCA modified Xenopus GLP-1 conjugates were designed (4a-r), and the bioactivity studies of these conjugates were performed to identify compounds with balanced in vitro receptor activation potency and plasma stability...
May 25, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29799100/no-qtc-prolongation-with-semaglutide-a-thorough-qt-study-in-healthy-subjects
#2
Valentin Demmel, Anne Sandberg-Schaal, Jacob B Jacobsen, Georg Golor, Jonas Pettersson, Anne Flint
INTRODUCTION: Semaglutide is a glucagon-like peptide-1 (GLP-1) analog approved for the once-weekly treatment of type 2 diabetes. The objective of this 16-week, double-blind, single-center thorough QT study was to confirm that semaglutide treatment does not prolong cardiac repolarization versus placebo. Prolongation of the QT interval is a biomarker for ventricular tachyarrhythmia. METHODS: In a parallel design, 168 healthy subjects were randomized to the treatment or placebo arms, of whom 166 were treated with subcutaneous semaglutide (N = 83; escalated to a supratherapeutic dose of 1...
May 24, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29779196/retrospective-analysis-of-an-insulin-to-liraglutide-switch-in-patients-with-type-2-diabetes-mellitus
#3
Eveline Bruinstroop, Laura Meyer, Catherine B Brouwer, Diana E van Rooijen, P Sytze van Dam
INTRODUCTION: Insulin and the GLP-1 receptor agonist liraglutide are both effective in reaching glycemic targets. The efficacy of an insulin-to-liraglutide switch in an obese population with concurrent use of sulfonylurea and metformin is unknown. We assessed the efficacy and determinants of success of an insulin-to-liraglutide switch in these patients. METHODS: In a retrospective study we analyzed all patients that underwent an insulin-to-liraglutide switch during routine medical care (January 2009-February 2015)...
June 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29760945/liraglutide-and-dulaglutide-therapy-in-addition-to-sglt-2-inhibitor-and-metformin-treatment-in-indian-type-2-diabetics-a-real-world-retrospective-observational-study
#4
S Ghosal, B Sinha
Background: Therapy for Type 2 diabetes (T2D) has been transformed by the introduction of newer agents like Glucagon like Peptide Receptor Agonists (GLP-1RA) and Sodium-glucose linked transporter inhibitors (SGLT2i). However with co-initiation of SGLT2i and GLP-1RA in the DURATION 8 trial an improvement in HbA1c was noted but the beneficial effect was not equal to the sum of its parts. In view of this we proceeded to test the hypothesis that sequential addition of GLP-1RA therapy to metformin and SGLT-2i may be more beneficial...
2018: Clinical Diabetes and Endocrinology
https://www.readbyqxmd.com/read/29525885/utilization-patterns-of-glucagon-like-peptide-1-receptor-agonists-in-patients-with-type-2-diabetes-mellitus-in-italy-a-retrospective-cohort-study
#5
Marco Orsini Federici, Janette McQuillan, Giovanni Biricolti, Serena Losi, Jeremie Lebrec, Catrina Richards, Cristiana Miglio, Kirsi Norrbacka
INTRODUCTION: Real-world evidence on glucagon-like peptide-1 receptor agonist (GLP-1 RAs) usage is emerging in different European countries but is lacking in Italy. This retrospective cohort study aimed to describe the real-world drug utilization patterns in patients initiating GLP-1 RAs for treating T2DM in Italy. METHODS: Adults aged ≥ 20 years and with ≥ 1 oral antidiabetic drug (alone or in combination with insulin) other than GLP-1 RAs in the 6 months prior to initiating exenatide twice daily (exBID), exenatide once weekly (exQW), dulaglutide once weekly (DULA), liraglutide once daily (LIRA) or lixisenatide once daily (LIXI) between March and July 2016 were retrospectively identified in the Italian IMS LifeLink™ longitudinal prescriptions database (retail pharmacy data)...
April 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29516612/use-and-effectiveness-of-dapagliflozin-in-routine-clinical-practice-an-italian-multicentre-retrospective-study
#6
Gian Paolo Fadini, Giancarlo Zatti, Ileana Baldi, Daniele Bottigliengo, Agostino Consoli, Andrea Giaccari, Giorgio Sesti, Angelo Avogaro
In randomized controlled trials (RCTs), sodium-glucose co-transporter-2 (SGLT2) inhibitors have been shown to confer glycaemic and extra-glycaemic benefits. The DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) study was a multicentre retrospective study designed to evaluate the baseline characteristics of patients receiving dapagliflozin vs those receiving selected comparators (dipeptidyl peptidase-4 inhibitors, gliclazide, or glucagon-like peptide-1 receptor agonists), and drug effectiveness in routine clinical practice...
March 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29397532/changes-in-heart-rate-associated-with-exenatide-once-weekly-pooled-analysis-of-clinical-data-in-patients-with-type-2-diabetes
#7
Steven P Marso, Elise Hardy, Jenny Han, Hui Wang, Robert J Chilton
INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycemia in patients with type 2 diabetes, but heart rate increases have been observed. METHODS: A pooled post hoc analysis of 11 randomized clinical trials (N = 4595) of 10-30 weeks' duration from the exenatide once-weekly (QW) development program evaluated heart rate with exenatide QW (intervention group) and exenatide twice daily (BID), liraglutide, and non-GLP-1RAs (insulin, metformin, pioglitazone, and sitagliptin) (comparison groups)...
April 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29395808/effect-of-short-term-intensive-insulin-therapy-on-the-incretin-response-in-early-type-2-diabetes
#8
H Choi, C K Kramer, B Zinman, P W Connelly, R Retnakaran
AIMS: Short-term intensive insulin therapy (IIT) and gastric bypass surgery are both interventions that can improve beta-cell function, reduce insulin resistance and induce remission of type 2 diabetes. Whereas gastric bypass yields an enhanced glucagon-like peptide-1 (GLP-1) response that may contribute to its metabolic benefits, the effect of short-term IIT on the incretin response is unclear. Thus, we sought to evaluate the impact of IIT on GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion in early type 2 diabetes...
January 11, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29369494/comparisons-of-diabetic-retinopathy-events-associated-with-glucose-lowering-drugs-in-patients-with-type-2-diabetes-mellitus-a-network-meta-analysis
#9
Huilin Tang, Guangyao Li, Ying Zhao, Fei Wang, Emily W Gower, Luwen Shi, Tiansheng Wang
AIM: To assess the comparative effects of glucose-lowering drugs (GLDs) on the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). METHODS: We systematically searched Cochrane Central Register of Controlled Trials, PUBMED and EMBASE from inception to January 17, 2017 to identify randomized controlled trials (RCTs) that reported DR events among T2DM patients receiving any GLD. Random-effects pairwise and network meta-analyses were performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs)...
January 25, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29357718/the-cost-effectiveness-of-dulaglutide-versus-insulin-glargine-for-the-treatment-of-type-2-diabetes-mellitus-in-japan
#10
Hitoshi Ishii, Matthew Madin-Warburton, Alena Strizek, Lucy Thornton-Jones, Shuichi Suzuki
AIMS: Dulaglutide is a new once weekly glucagon-like peptide-1 (GLP-1) receptor agonist administered via a disposable auto-injection pen for the management of type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the cost-effectiveness of dulaglutide vs insulin glargine for the management of T2DM from a Japanese healthcare perspective, in accordance with recently approved Japanese Cost-Effectiveness Guidelines. METHODS: The IQVIA CORE Diabetes Model (version 9) was used to estimate the long-term costs and effects of treatment with dulaglutide and insulin glargine...
May 2018: Journal of Medical Economics
https://www.readbyqxmd.com/read/29320889/the-cardiovascular-effect-of-incretin-based-therapies-among-type-2-diabetes-a-systematic-review-and-network-meta-analysis
#11
REVIEW
Shanshan Wu, Andrea Cipriani, Zhirong Yang, Jun Yang, Ting Cai, Yang Xu, Xiaochi Quan, Yuan Zhang, Sanbao Chai, Feng Sun, Siyan Zhan
OBJECTIVE: To evaluate the comparative cardiovascular safety of incretin-based therapies in patients with type 2 diabetes mellitus (T2DM). METHODS: Medline, Embase, the Cochrane Library and www.clinicaltrials.gov were searched for randomized controlled trials (RCTs) with duration≥12 weeks. Network meta-analysis was performed, followed by subgroup analysis and meta-regression. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence...
March 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29301824/clinical-impact-of-itca-650-a-novel-drug-device-glp-1-receptor-agonist-in-uncontrolled-type-2-diabetes-and-very-high-baseline-hba-1c-the-freedom-1-hbl-high-baseline-study
#12
Robert R Henry, Julio Rosenstock, Douglas S Denham, Prakash Prabhakar, Lise Kjems, Michelle A Baron
OBJECTIVE: ITCA 650 is a subdermal osmotic mini-pump that continuously delivers exenatide subcutaneously for 3-6 months. The efficacy, safety, and tolerability of ITCA 650 added to diet and exercise alone or combined with metformin, sulfonylurea, or thiazolidinedione monotherapy or a combination of these drugs was evaluated in poorly controlled patients with type 2 diabetes (T2D) who were ineligible for participation in a placebo-controlled study (FREEDOM-1) because of severe hyperglycemia (HbA1c >10% [86 mmol/mol])...
March 2018: Diabetes Care
https://www.readbyqxmd.com/read/29283894/incretin-based-drugs-and-the-incidence-of-colorectal-cancer-in-patients-with-type-2-diabetes
#13
Devin Abrahami, Hui Yin, Oriana H Y Yu, Michael N Pollak, Laurent Azoulay
BACKGROUND: Evidence on the safety of the incretin-based drugs (glucagon-like peptide-1 [GLP-1] analogues and dipeptidyl peptidase-4 [DPP-4] inhibitors) with respect to colorectal cancer is contradictory. The objective of this study was to determine whether use of incretin-based drugs is associated with risk of incident colorectal cancer in patients with type 2 diabetes. METHODS: Using data from the UK Clinical Practice Research Datalink, we identified a cohort of 112,040 patients newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2015...
March 2018: Epidemiology
https://www.readbyqxmd.com/read/29239601/preparation-and-pharmaceutical-characterizations-of-lipidated-dimeric-xenopus-glucagon-like-peptide-1-conjugates
#14
Jing Han, Feng Zhou, Yingying Fei, Xinyu Chen, Junjie Fu, Hai Qian
A pair of glucagon-like peptide-1 (GLP-1) analogs (1 and 2) were synthesized by hybridizing the key sequences of GLP-1, exendin-4, lixisenatide, and xenGLP-1B (Xenopus GLP-1 analog). To achieve long-acting hypoglycemic effects and to further improve their anti-diabetic potencies, lipidization and dimerization strategies were used to afford two lipidated dimeric conjugates (9 and 11). Conjugates 9 and 11 showed stronger receptor activation potency than GLP-1 and exendin-4 in vitro. Moreover, 9 and 11 exhibited superior hypoglycemic and insulinotropic activities to liraglutide in type 2 diabetic C57BL/6J-m+/+ Leprdb (db/db) mice...
February 21, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29235507/blood-brain-glucose-transfer-in-alzheimer-s-disease-effect-of-glp-1-analog-treatment
#15
Michael Gejl, Birgitte Brock, Lærke Egefjord, Kim Vang, Jørgen Rungby, Albert Gjedde
There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral metabolic rate for glucose (CMRglc ) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29205774/comparison-of-glucose-lowering-agents-after-dual-therapy-failure-in-type-2-diabetes-a-systematic-review-and-network-meta-analysis-of-randomized-controlled-trials
#16
Francesco Zaccardi, Nafeesa N Dhalwani, Jolyon Dales, Hamid Mani, Kamlesh Khunti, Melanie J Davies, David R Webb
AIMS: To assess the evidence supporting the choice of third-line agents in adults with inadequately controlled type 2 diabetes. MATERIALS AND METHODS: We searched randomized controlled trials (RCTs) published between January 2000 and July 2017 that reported data on cardiometabolic outcomes and hypoglycaemia for glucose-lowering agents added to metformin-based dual treatments. Data were stratified by background therapy and RCT duration, and synthesized, when possible, with network meta-analyses...
April 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29183873/effect-of-chronic-liraglutide-therapy-and-its-withdrawal-on-time-to-postchallenge-peak-glucose-in-type-2-diabetes
#17
Susan Tran, Caroline K Kramer, Bernard Zinman, Haysook Choi, Ravi Retnakaran
Delayed timing of peak serum glucose following an oral glucose challenge can predict declining β-cell function and worsening glucose tolerance over time. Accordingly, postchallenge peak glucose is typically delayed in patients with type 2 diabetes (T2DM). However, little is known about the capacity of antidiabetic medications to reverse this delay. Thus, we sought to evaluate the effect of the glucagon-like peptide-1 agonist liraglutide on time to peak glucose in early T2DM. In this secondary analysis of a double-blind placebo-controlled trial, 51 patients with T2DM of 2...
March 1, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29180139/combined-gastrin-releasing-peptide-29-and-glucagon-like-peptide-1-reduce-body-weight-more-than-each-individual-peptide-in-diet-induced-obese-male-rats
#18
Thaer R Mhalhal, Martha C Washington, Kayla D Newman, John C Heath, Ayman I Sayegh
To test the hypothesis that gastrin releasing peptide-29 (GRP-29) combined with glucagon like peptide-1 (7-36) (GLP-1 (7-36)) reduce body weight (BW) more than each of the peptides given individually, we infused the two peptides (0.5nmol/kg each) in the aorta of free feeding, diet-induced obese (DIO) male Sprague Dawley rats once daily for 25days and measured BW. We found that GRP-29 and GLP-1 reduce BW, GRP-29 reduced it more than GLP-1 and GRP-29+GLP-1 reduce BW more than each peptide given alone. This reduction was accompanied by decrease 24-hour food intake (normal rat chow), meal size (MS), duration of first meal and number of meals, and increase latency to the first meal, intermeal interval (IMI) and satiety ratio (IMI/MS, amount of food consumed per a unit of time)...
February 2018: Neuropeptides
https://www.readbyqxmd.com/read/29171021/xenopus-derived-glucagon-like-peptide-1-and-polyethylene-glycosylated-glucagon-like-peptide-1-receptor-agonists-long-acting-hypoglycaemic-and-insulinotropic-activities-with-potential-therapeutic-utilities
#19
Jing Han, Yingying Fei, Feng Zhou, Xinyu Chen, Ying Zhang, Lin Liu, Junjie Fu
BACKGROUND AND PURPOSE: Incretin-based therapies based on glucagon-like peptide-1 (GLP-1) receptor agonists are effective treatments of type 2 diabetes. Abundant research has focused on the development of long-acting GLP-1 receptor agonists. However, all GLP-1 receptor agonists in clinical use or development are based on human or Gila GLP-1. We have identified a potent GLP-1 receptor agonist, xGLP-1B, based on Xenopus GLP-1. EXPERIMENTAL APPROACH: To further modify the structure of xGLP-1B, alanine scanning was performed to study the structure -activity relationship of xGLP-1B...
February 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29167470/glucagon-like-peptide-1-mimetics-optimal-for-asian-type-2-diabetes-patients-with-and-without-overweight-obesity-meta-analysis-of-randomized-controlled-trials
#20
Fang Zhang, Lizhi Tang, Yuwei Zhang, Qingguo Lü, Nanwei Tong
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are desirable for diabetes, especially in patients with overweight/obesity. We aimed to determine whether GLP-1RAs exhibit different glucose-lowering efficacies between Asian type 2 diabetes (T2D) patients with and without overweight/obesity. Randomized controlled trials were searched in EMBASE, MEDLINE, CENTRAL, and ClinicalTrials.gov. Studies published in English with treatment duration ≥12 weeks and information on HbA1c changes were included. The studies were divided into normal body mass index (BMI) and overweight/obese groups according to baseline BMI...
November 22, 2017: Scientific Reports
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