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GLP-1 diabetes

Zeinab Nazarian-Samani, Robert D E Sewell, Zahra Lorigooini, Mahmoud Rafieian-Kopaei
PURPOSE OF REVIEW: This systematic review describes evidence concerning medicinal plants that, in addition to exerting hypoglycemic effects, decrease accompanying complications such as nephropathy, neuropathy, retinopathy, hypertension, and/or hyperlipidemia among individuals with diabetes mellitus (DM). RECENT FINDINGS: Studies on the antidiabetic mechanisms of medicinal plants have shown that most of them produce hypoglycemic activity by stimulating insulin secretion, augmenting peroxisome proliferator-activated receptors (PPARs), inhibiting α-amylase or α-glucosidase, glucagon-like peptide-1 (GLP-1) secretion, advanced glycation end product (AGE) formation, free radical scavenging plus antioxidant activity (against reactive oxygen or nitrogen species (ROS/RNS)), up-regulating or elevating translocation of glucose transporter type 4 (GLUT-4), and preventing development of insulin resistance...
August 13, 2018: Current Diabetes Reports
Hsien-Yen Chang, Sonal Singh, Omar Mansour, Sheriza Baksh, G Caleb Alexander
Importance: Results of clinical trials suggest that canagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor for treating type 2 diabetes, may be associated with lower extremity amputation. Objective: To quantify the association between the use of oral medication for type 2 diabetes and 5 outcomes (lower extremity amputation, peripheral arterial disease, critical limb ischemia, osteomyelitis, and ulcer). Design, Setting, and Participants: A retrospective cohort study was conducted using Truven Health MarketScan Commercial Claims and Encounters data on new users between September 1, 2012, and September 30, 2015...
August 13, 2018: JAMA Internal Medicine
Moellmann Julia, Klinkhammer Barbara Mara, Onstein Julia, Stöhr Robert, Jankowski Vera, Jankowski Joachim, Lebherz Corinna, Tacke Frank, Marx Nikolaus, Boor Peter, Lehrke Michael
Incretin based therapies, including GLP-1 receptor agonists and dipeptidylpeptidase 4 (DPP-4) inhibitors, are potent glucose lowering drugs. Still, only GLP-1 receptor agonists with close peptide homology to GLP-1 (liraglutide and semaglutide) but neither exenatide based GLP-1 receptor agonists nor DPP-4 inhibitors were found to reduce cardiovascular events. This different response might relate to GLP-1 receptor independent actions of GLP-1 caused by cleavage products only liberated by GLP-1 receptor agonists with close peptide structure to GLP-1...
August 13, 2018: Diabetes
Bo-Ram Kim, Hyo Young Kim, Inhee Choi, Jin-Baek Kim, Chang Hyun Jin, Ah-Reum Han
Dipeptidyl peptidase IV (DPP-IV), a new target for the treatment of type 2 diabetes mellitus, degrades incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide. DPP-IV inhibitors shorten the inactivation of GLP-1, permitting the incretin to stimulate insulin release, thereby combating hyperglycemia. In our ongoing search for new DPP-IV inhibitors from medicinal plants and foods, three flavonol glycosides ( 1 ⁻ 3 ) were isolated from the seeds of Lens culinaris Medikus (Fabaceae) and tested for their DPP-IV⁻inhibitory activity...
August 10, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Xuejing Li, Suhui Qie, Xianying Wang, Yingying Zheng, Yang Liu, Guoqiang Liu
OBJECTIVES: To investigate the safety and efficacy of once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide as monotherapy or add-on to other antihyperglycaemic agents (AHAs) in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, Embase, Cochrane library and were searched from the inception to January 18, 2018. Randomised controlled trials (RCTs) comparing semaglutide with placebo or other AHAs in T2DM patients were included in our meta-analysis...
August 12, 2018: Endocrine
Bo Ahrén
GLP-1 receptor agonists are today established glucose-lowering drugs in the management of type 2 diabetes. Their development emerged from the understanding that a combined islet dysfunction comprising of impaired insulin secretion and exaggerated glucagon secretion is the key defect for the hyperglycemia. GLP-1 was early shown to target these defects and following the realization that DPP-4 inactivates native GLP-1, several different DPP-4 resistant GLP-1 receptor agonists have been developed. They are administered subcutaneously but show differences in molecular structure, molecular size and pharmacokinetics, the latter allowing twice daily, once daily or once weekly administration...
August 12, 2018: Journal of Diabetes Investigation
Kathleen T Watson, Tonita E Wroolie, Gabby Tong, Lara C Foland-Ross, Sophia Frangou, Manpreet Singh, Roger McIntyre, Siena Roat-Shumway, Alison Myoraku, Allan L Reiss, Natalie L Rasgon
Insulin resistance (IR) is a metabolic state preceding development of type 2 diabetes (DM2), cardiovascular disease, and neurodegenerative disorders, including Alzheimer's Disease (AD). Liraglutide, a glucagon-like peptide-1 (GLP) agonist, is an insulin-sensitizing agent with neuroprotective properties, as shown in animal studies. The purpose of this double-blinded, placebo-controlled study was to examine the neural effects of administration of liraglutide in cognitively normal late middle-aged individuals with subjective cognitive complaints (half of subjects had family history of AD)...
August 9, 2018: Behavioural Brain Research
Matthias Kolibabka, Nadine Dietrich, Thomas Klein, Hans-Peter Hammes
AIMS/HYPOTHESIS: Linagliptin has protective effects on the retinal neurovascular unit but, in proliferative retinopathy, dipeptidyl peptidase 4 (DPP-4) inhibition could be detrimental. The aim of this study was to assess the effect of linagliptin on ischaemia-induced neovascularisation of the retina. METHODS: C57BL/6J and glucagon-like peptide 1 (GLP-1) receptor (Glp1r)-/- mice were subjected to a model of oxygen-induced retinopathy (OIR). Both strains were subcutaneously treated with linagliptin from postnatal days 12 to 16...
August 10, 2018: Diabetologia
Jing Han, Yue Huang, Xinyu Chen, Feng Zhou, Yingying Fei, Junjie Fu
Dimerization is viewed as an effective means to enhance the binding affinity and therapeutic potency of peptides. Both dimerization and lipidation effectively prolong the half-life of peptides in vivo by increasing hydrodynamic size and facilitating physical interactions with serum albumin. Here, we report a novel method to discover long-acting glucagon-like peptide 1 (GLP-1) analogues by rational design based on Xenopus GLP-1 through a combined dimerization and lipidization strategy. On the basis of our previous structure analysis of Xenopus GLP-1, palmitic acid and a C-terminal Cys were firstly introduced into two Xenopus GLP-1 analogues (1 and 2), and the afforded 3 and 4 were further reacted with bis-maleimide amine to afford two dimeric lipidated Xenopus GLP-1 analogues (5 and 6)...
August 3, 2018: European Journal of Medicinal Chemistry
Joachim Tillner, Maximilian G Posch, Frank Wagner, Lenore Teichert, Youssef Hijazi, Christine Einig, Stefanie Keil, Torsten Haack, Michael Wagner, Martin Bossart, Philip J Larsen
AIMS: To evaluate the safety, pharmacokinetics, and pharmacodynamics of SAR425899, a novel polypeptide active as an agonist at both the glucagon-like peptide-1 receptor (GLP-1 R) and the glucagon receptor, in healthy volunteers and in patients with overweight/obesity and type 2 diabetes. METHODS: Subcutaneous administrations of SAR425899 were tested in two randomized, placebo-controlled, double-blind clinical trials. In the first trial, healthy overweight volunteers (BMI: 25─30 kg/m2 ; n = 32) received single-ascending doses (0...
August 8, 2018: Diabetes, Obesity & Metabolism
Clifford J Bailey, Nikolaus Marx
This review examines recent randomised controlled cardiovascular (CV) outcome trials with glucose-lowering therapies in type 2 diabetes and their impact on the treatment of patients with type 2 diabetes. The trials were designed to comply with regulatory requirements to confirm that major adverse cardiac events (MACE) are not detrimrntally affected by such therapies. Trials involving dipeptidyl peptidase-4 (DPP4) inhibitors did not alter a composite MACE comprising CV deaths, nonfatal myocardial infarction (MI) and non-fatal stroke...
August 8, 2018: Diabetes, Obesity & Metabolism
Lawrence Blonde, Vivian Fonseca
A growing body of data, guideline recommendations, algorithms, and position papers supports the use of glucagon-like peptide-1 (GLP-1) receptor agonists in type 2 diabetes (T2D), given their beneficial effects on glycemic control, weight, lipid parameters, and blood pressure, and low risk for hypoglycemia when used in patients who have not achieved glycemic goals with metformin and lifestyle interventions. Exciting new evidence continues to emerge, showing the utility of certain GLP-1 receptor agonists to decrease incident cardiovascular (CV) outcomes, and to bolster glycemic control when combined with other antihyperglycemic therapies, including basal insulin...
August 7, 2018: Endocrine Practice
Gabby Elbaz-Greener, Olga Bloch, Ilya Kumets, Alex Blatt, Micha J Rapoport
We previously demonstrated increased GLP-1 secretion during acute ST elevation myocardial infarction (STEMI) in non-diabetic (ND) patients. Whether the endogenous GLP-1 system response is different in patients with type 2 diabetes (T2D) during STEMI is unknown. Patients with STEMI (20 ND, 13 T2D) and three control groups: non-STEMI (14 ND,13 T2D), stable angina pectoris (SAP) (8 ND, 10 T2D) patients and healthy subjects (n=25) were studied. Plasma levels of total and active GLP-1 and soluble DPP-4 (sDPP4) were estimated by ELISA on admission and 24, 48 hours after percutaneous coronary intervention (PCI) in all patients...
August 6, 2018: Diabetes, Obesity & Metabolism
Y S Zhang, W Y Weng, B C Xie, Y Meng, Y H Hao, Y M Liang, Z K Zhou
Our network meta-analysis analyzed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk. By combining data from randomized controlled trials, we found that GLP-1 RAs were associated with a decreased bone fracture risk, and exenatide is the best option agent with regard to the risk of fracture. This study is registered with PROSPERO (CRD42018094433). INTRODUCTION: Data on the effects of GLP-1 RAs on fracture risk are conflicted. This study aimed to analyze the available evidence on the effects of GLP-1 RAs on fracture risk in type 2 diabetes mellitus patients...
August 6, 2018: Osteoporosis International
Masahiro Kawatani, Yuichiro Yamada, Masahito Kawatani
Glucagon-like peptide-1 (GLP-1) is a peptide hormone and member of the incretin family. GLP-1 related drugs, such as liraglutide, are widely used to treat diabetic patients and work by stimulating pancreatic β cells to increase glucose-dependent insulin secretion. However, extrapancreatic effects, such as appetite suppression or emesis, are observed in response to GLP-1 receptor agonists. In this study we used the in vitro patch-clamp method in acute brainstem preparations of mice and demonstrated that GLP-1 acts directly on area postrema neurons...
August 3, 2018: Peptides
Xiang Li, Zhangrong Xu, Linong Ji, Lixin Guo, Jing Liu, Kun Feng, Yushan Xu, Dalong Zhu, Weiping Jia, XinWu Ran, Limin Chen, Shi Zhao, Bingying Shi, Jun Zhu, Zongyan Shan, Zhiguang Zhou, Longyi Zeng, Jianping Weng
AIMS/INTRODUCTION: To investigate the direct medical costs for patients with type 2 diabetes in China and to examine the influencing factors. MATERIALS AND METHODS: In this multicenter study, 1070 patients with type 2 diabetes from sixteen tertiary hospitals in fourteen major cities of China were enrolled. Patient data and direct medical costs were collected during a follow-up period of six months at intervals of one month. The log-transformed direct medical costs were fiwere by generalized estimation equation to indicator variables for demographics, metabolic control, treatments, complications and comorbidities...
August 5, 2018: Journal of Diabetes Investigation
Takahiro Takase, Akinobu Nakamura, Chiho Yamamoto, Hiroshi Nomoto, Aika Miya, Midori Dannoura, Kyu Yong Cho, Yoshio Kurihara, Naoki Manda, Shin Aoki, Tatsuya Atsumi, Hideaki Miyoshi
AIMS/INTRODUCTION: We compared treatment satisfaction in type 2 diabetes patients taking daily and weekly glucagon-like peptide-1 (GLP-1) receptor agonists. MATERIALS AND METHODS: The study was a 12-week, multicenter, open-label, prospective, randomized, parallel-group comparison trial. The participants were Japanese patients with type 2 diabetes being administered with the GLP-1 receptor agonist liraglutide daily for more than 3 months. Patients were randomly assigned to either continue taking liraglutide once daily (Lira group) or to switch to dulaglutide once weekly (Dula group)...
August 4, 2018: Journal of Diabetes Investigation
Niina Matikainen, Sanni Söderlund, Elias Björnson, Kirsi Pietiläinen, Antti Hakkarainen, Nina Lundbom, Marja-Riitta Taskinen, Jan Borén
AIMS/HYPOTHESIS: Subjects with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) exhibit considerable residual risk for cardiovascular disease (CVD). There is therefore increasing interest in targeting postprandial lipid metabolism and remnant cholesterol. Treatment with the glucagon-like peptide 1 (GLP-1) analogue liraglutide reduces CVD risk by partly unexplained mechanisms. Here we investigated the effects of liraglutide intervention on ectopic fat depots, hepatic lipogenesis and fat oxidation, postprandial lipid metabolism and glycaemia in humans with type 2 diabetes...
August 2, 2018: Diabetes, Obesity & Metabolism
Enji Reda, Sherifa Hassaneen, Hanan S El-Abhar
Bromocriptine (BC), a sympatholytic dopaminergic D2 receptor agonist, has been comprehensively used in clinic to treat Parkinson's disease (PD) and prolactinomas. Besides, BC represents a novel therapeutic option in type 2 diabetes (T2DM); however, the precise mechanisms are not completely unveiled. Hence, the objective of the current work is to clarify the potential molecular pathways of the insulin sensitizing effect of BC in the skeletal muscle of diabetic rats and to evaluate its possible interaction with sitagliptin (SG) as an add-on therapy...
2018: Frontiers in Pharmacology
Seungbin Cha, Sun Hwa Lee, Sung Hun Kang, Mohammad Nazmul Hasan, Young Jun Kim, Sungpil Cho, Yong-Kyu Lee
Background: Diabetes mellitus (DM) is a chronic progressive metabolic disease that involves uncontrolled elevation of blood glucose levels. Among various therapeutic approaches, GLP-1 prevents type 2 diabetes mellitus (T2DM) patients from experiencing hyperglycemic episodes. However, the short half-life (< 5 min) and rapid clearance of GLP-1 often limits its therapeutic use. Here, we developed an oral GLP-1 gene delivery system to achieve an extended antidiabetic effect. Methods: Human IgG1 (hIgG1)-Fc-Arg/pDNA complexes were prepared by an electrostatic complexation of the expression plasmid with various ratios of the positively modified Fc fragments of an antibody (hIgG1-Fc-Arg) having a targeting ability to FcRn receptor...
2018: Biomaterials Research
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