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      Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes

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          To simplify administration of aqueous exenatide once weekly, which requires reconstitution, the exenatide microspheres have been reformulated in a ready‐to‐use autoinjector with a Miglyol diluent (exenatide QWS‐AI). This study compared the efficacy and safety of exenatide QWS‐AI with the first‐in‐class glucagon‐like peptide‐1 receptor agonist exenatide twice daily ( BID).

          Materials and Methods

          This randomized, open‐label, controlled study in patients with type 2 diabetes using diet and exercise or taking stable oral glucose‐lowering medication randomized patients 3:2 to either exenatide QWS‐AI (2 mg) or exenatide BID (10 μg) for 28 weeks. The primary outcome was the 28‐week change in glycated haemoglobin ( HbA1c). A subset of patients completed a standardized meal test for postprandial and pharmacokinetic assessments.


          A total of 375 patients (mean HbA1c, 8.5% [69 mmol/mol]; body mass index, 33.2 kg/m 2; diabetes duration, 8.5 years) received either exenatide QWS‐AI (n = 229) or exenatide BID (n = 146); HbA1c was reduced by −1.4% and −1.0%, respectively (least‐squares mean difference, −0.37%; P = .0072). More patients achieved HbA1c <7.0% with exenatide QWS‐AI (49.3%) than with exenatide BID (43.2%; P = .225). Body weight was reduced in both groups ( P = .37 for difference). Gastrointestinal adverse events ( AEs) were reported in 22.7% (exenatide QWS‐AI) and 35.6% (exenatide BID) of patients; fewer patients in the exenatide QWS‐AI group withdrew because of AEs than in the exenatide BID group. Minor hypoglycaemia occurred most often with concomitant sulfonylurea use.


          Exenatide QWS‐AI was associated with a greater reduction in HbA1c, similar weight loss and a favorable gastrointestinal AE profile compared with exenatide BID.

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          Most cited references 10

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          GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus.

           Juris Meier (2012)
          In healthy humans, the incretin glucagon-like peptide 1 (GLP-1) is secreted after eating and lowers glucose concentrations by augmenting insulin secretion and suppressing glucagon release. Additional effects of GLP-1 include retardation of gastric emptying, suppression of appetite and, potentially, inhibition of β-cell apoptosis. Native GLP-1 is degraded within ~2-3 min in the circulation; various GLP-1 receptor agonists have, therefore, been developed to provide prolonged in vivo actions. These GLP-1 receptor agonists can be categorized as either short-acting compounds, which provide short-lived receptor activation (such as exenatide and lixisenatide) or as long-acting compounds (for example albiglutide, dulaglutide, exenatide long-acting release, and liraglutide), which activate the GLP-1 receptor continuously at their recommended dose. The pharmacokinetic differences between these drugs lead to important differences in their pharmacodynamic profiles. The short-acting GLP-1 receptor agonists primarily lower postprandial blood glucose levels through inhibition of gastric emptying, whereas the long-acting compounds have a stronger effect on fasting glucose levels, which is mediated predominantly through their insulinotropic and glucagonostatic actions. The adverse effect profiles of these compounds also differ. The individual properties of the various GLP-1 receptor agonists might enable incretin-based treatment of type 2 diabetes mellitus to be tailored to the needs of each patient.
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            Potential of Albiglutide, a Long-Acting GLP-1 Receptor Agonist, in Type 2 Diabetes

            OBJECTIVE To evaluate the efficacy, safety, and tolerability of incremental doses of albiglutide, a long-acting glucagon-like peptide-1 receptor agonist, administered with three dosing schedules in patients with type 2 diabetes inadequately controlled with diet and exercise or metformin monotherapy. RESEARCH DESIGN AND METHODS In this randomized multicenter double-blind parallel-group study, 356 type 2 diabetic subjects with similar mean baseline characteristics (age 54 years, diabetes duration 4.9 years, BMI 32.1 kg/m2, A1C 8.0%) received subcutaneous placebo or albiglutide (weekly [4, 15, or 30 mg], biweekly [15, 30, or 50 mg], or monthly [50 or 100 mg]) or exenatide twice daily as an open-label active reference (per labeling in metformin subjects only) over 16 weeks followed by an 11-week washout period. The main outcome measure was change from baseline A1C of albiglutide groups versus placebo at week 16. RESULTS Dose-dependent reductions in A1C were observed within all albiglutide schedules. Mean A1C was similarly reduced from baseline by albiglutide 30 mg weekly, 50 mg biweekly (every 2 weeks), and 100 mg monthly (−0.87, −0.79, and −0.87%, respectively) versus placebo (−0.17%, P < 0.004) and exenatide (−0.54%). Weight loss (−1.1 to −1.7 kg) was observed with these three albiglutide doses with no significant between-group effects. The incidence of gastrointestinal adverse events in subjects receiving albiglutide 30 mg weekly was less than that observed for the highest biweekly and monthly doses of albiglutide or exenatide. CONCLUSIONS Weekly albiglutide administration significantly improved glycemic control and elicited weight loss in type 2 diabetic patients, with a favorable safety and tolerability profile.
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              Exenatide twice daily versus glimepiride for prevention of glycaemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA): an open-label, randomised controlled trial.

              Glycaemic control deteriorates progressively over time in patients with type 2 diabetes. Options for treatment escalation remain controversial after failure of first-line treatment with metformin. We compared add-on exenatide with glimepiride for durability of glycaemic control in patients with type 2 diabetes inadequately controlled by metformin alone. We did an open-label, randomised controlled trial at 128 centres in 14 countries between Sept 5, 2006, and March 29, 2011. Patients aged 18-85 years with type 2 diabetes inadequately treated by metformin were randomly assigned via a computer-generated randomisation sequence to receive exenatide twice daily or glimepiride once daily as add-on to metformin. Randomisation was stratified by predetermined categories of glycated haemoglobin (HbA(1C)) concentration. The primary outcome was time to inadequate glycaemic control and need for alternative treatment, defined as an HbA(1c) concentration of more than 9% after the first 3 months of treatment, or more than 7% at two consecutive visits after the first 6 months. Analysis was by intention to treat. This trial is registered with EudraCT, number 2005-005448-21, and ClinicalTrials.gov, number NCT00359762. We randomly assigned 515 patients to the exenatide group and 514 to the glimepiride group, of whom 490 versus 487 were the intention-to-treat population. 203 (41%) patients had treatment failure in the exenatide group compared with 262 (54%) in the glimepiride group (risk difference 12·4 [95% CI 6·2-18·6], hazard ratio 0·748 [0·623-0·899]; p=0·002). 218 (44%) of 490 patients in the exenatide group, and 150 (31%) of 487 in the glimepiride group achieved an HbA(1c) concentration of less than 7% (p<0·0001), and 140 (29%) versus 87 (18%) achieved concentrations of 6·5% and less (p=0·0001). We noted a significantly greater decrease in bodyweight in patients given exenatide than in those given glimepiride (p<0·0001). Five patients in each treatment group died from causes unrelated to treatment. Significantly fewer patients in the exenatide group than in the glimepiride group reported documented symptomatic (p<0·0001), nocturnal (p=0·007), and non-nocturnal (p<0·0001) hypoglycaemia. Discontinuation because of adverse events (mainly gastrointestinal) was significantly higher (p=0·0005) in the exenatide group than in the glimepiride group in the first 6 months of treatment, but not thereafter. These findings provide evidence for the benefits of exenatide versus glimepiride for control of glycaemic deterioration in patients with type-2 diabetes inadequately controlled by metformin alone. Eli Lilly and Company; Amylin Pharmaceuticals. Copyright © 2012 Elsevier Ltd. All rights reserved.

                Author and article information

                Diabetes Obes Metab
                Diabetes Obes Metab
                Diabetes, Obesity & Metabolism
                Blackwell Publishing Ltd (Oxford, UK )
                22 August 2017
                January 2018
                : 20
                : 1 ( doiID: 10.1111/dom.2018.20.issue-1 )
                : 165-172
                [ 1 ] Rockwood Clinic Spokane Washington
                [ 2 ] Dallas Diabetes Research Center at Medical City Dallas Texas
                [ 3 ] Bristol‐Myers Squibb Princeton New Jersey
                [ 4 ] AstraZeneca Gaithersburg Maryland
                Author notes
                [* ] Correspondence

                Carol H. Wysham MD, Rockwood Center for Diabetes and Endocrinology, 400 East Fifth Avenue, Spokane, Washington 99202. Email: cwysham@ 123456rockwoodclinic.com

                © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                Page count
                Figures: 2, Tables: 2, Pages: 8, Words: 5429
                Funded by: Bristol‐Myers Squibb
                Funded by: AstraZeneca
                Original Article
                Original Articles
                Custom metadata
                January 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.8 mode:remove_FC converted:11.12.2017


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