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      Changes in glycemic variability, gastric emptying and vascular endothelial function after switching from twice-daily to once-weekly exenatide in patients with type 2 diabetes: a subpopulation analysis of the twin-exenatide study

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          Abstract

          Background

          We investigated the changes in blood glucose fluctuation, gastric emptying, and vascular endothelial function by switching from an exenatide twice-daily formulation (BID) to a once-weekly formulation (QW) since the evaluation of postprandial glucose excursion and glycemic variability (GV) by continuous glucose monitoring (CGM) after switching was lacking.

          Methods

          Twenty-nine patients with type 2 diabetes treated with exenatide BID were included in this study and switched to exenatide QW for 24 weeks. GV assessed by CGM, gastric emptying (by 13 C-acetate breath test) and vascular endothelial function (by reactive hyperemia - peripheral arterial tonometry) were evaluated at baseline and 24 weeks after switching.

          Results

          HbA1c decreased significantly from the baseline to week 24, while postprandial glucose levels after breakfast and dinner significantly increased (both P <0.05). However, the increases in GV indices were modest and not statistically significant at week 24. Vascular endothelial function was also not significantly changed after switching ( P >0.05). Gastric emptying was significantly accelerated at week 24 (T max 83.4 ± 12.1 min vs. 58.2 ± 16.4 min) ( P <0.001) and correlated with increased postprandial glucose levels after breakfast and dinner (both P <0.05).

          Conclusions

          Despite the increase in postprandial glucose associated with accelerated gastric emptying after switching from exenatide BID to QW, change in GV was modest and no significant deterioration in vascular endothelial function was observed after switching. These results support the superiority of treatment with exenatide QW over exenatide BID in clinical practice; however, attention should be paid to the monitoring and management of postprandial glucose levels when selecting exenatide QW.

          Trial registration

          Clinical trial registry number; UMIN000016390 and jRCTs031180320.

          Approval date of Registry and the Registration: December 12, 2014.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12902-022-00932-9.

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          Most cited references31

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          Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

          Rury R Holman, M Angelyn Bethel, Robert J Mentz … (2017)
          The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.
          Article 0 comments Cited 676 times – based on 0 reviews     Review now
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            9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2021

            (2020)
            The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc21-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc21-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
            Article 0 comments Cited 393 times – based on 0 reviews     Review now
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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.
              Article 0 comments Cited 391 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Yoshifumi Saisho: ysaisho@keio.jp
                Journal
                Journal ID (nlm-ta): BMC Endocr Disord
                Journal ID (iso-abbrev): BMC Endocr Disord
                Title: BMC Endocrine Disorders
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1472-6823
                Publication date (Electronic): 11 January 2022
                Publication date PMC-release: 11 January 2022
                Publication date Collection: 2022
                Volume: 22
                Electronic Location Identifier: 20
                Affiliations
                [1 ]GRID grid.26091.3c, ISNI 0000 0004 1936 9959, Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, , Keio University School of Medicine, ; Tokyo, Japan
                [2 ]GRID grid.26091.3c, ISNI 0000 0004 1936 9959, Center for Preventive Medicine, , Keio University School of Medicine, ; Tokyo, Japan
                [3 ]GRID grid.26091.3c, ISNI 0000 0004 1936 9959, Department of Internal Medicine, , Keio University School of Medicine, ; 35 Shinanomachi, Shinjuku-ku, 160-8582 Tokyo, Japan
                [4 ]GRID grid.26091.3c, ISNI 0000 0004 1936 9959, Division of Gastroenterology and Hepatology, Department of Internal Medicine, , Keio University School of Medicine, ; Tokyo, Japan
                Article
                Publisher ID: 932
                DOI: 10.1186/s12902-022-00932-9
                PMC ID: 8751111
                PubMed ID: 35016646
                SO-VID: 72144275-daac-43bc-9d3c-528a645adbbd
                Copyright © © The Author(s) 2022
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 2 November 2021
                Date accepted : 3 January 2022
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2022

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: type 2 diabetes,glp-1 receptor agonist,continuous glucose monitoring,gastric emptying
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: type 2 diabetes, glp-1 receptor agonist, continuous glucose monitoring, gastric emptying

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