Impact of polyethylene glycol loxenatide on cardiovascular outcomes in patients with type 2 diabetes: study protocol for a multicentre, randomised, double-blind, placebo-controlled trial (BALANCE-3).

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  • Additional Information
    • Source:
      Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101552874 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-6055 (Electronic) Linking ISSN: 20446055 NLM ISO Abbreviation: BMJ Open Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : BMJ Publishing Group Ltd, 2011-
    • Subject Terms:
      Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/drug therapy ; Cardiovascular Diseases*/etiology ; Cardiovascular Diseases*/prevention & control ; Cardiovascular Diseases*/drug therapy ; Myocardial Infarction*/complications; Humans ; Peptides/therapeutic use ; Polyethylene Glycols/therapeutic use ; Double-Blind Method ; Treatment Outcome ; Hypoglycemic Agents/therapeutic use ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic
    • Abstract:
      Introduction: Recent cardiovascular outcomes trials have demonstrated that glucagon-like peptide 1 receptor agonist (GLP-1RA) decreases the incidence of major adverse cardiovascular events (MACEs) in individuals with type 2 diabetes mellitus (T2DM). Polyethylene glycol loxenatide (PEG-Loxe) is a once-weekly GLP-1RA obtained by modifying exendin-4. No clinical trials have been designed to assess the impact of PEG-Loxe on cardiovascular (CV) outcomes in individuals with T2DM. This trial aims to test the hypothesis that compared with placebo, PEG-Loxe treatment does not result in an unacceptable increase in CV risk in individuals with T2DM.
      Methods and Analysis: This study is a multicentre, randomised, double-blind, placebo-controlled trial. Patients with T2DM who fulfilled the inclusion criteria were randomly divided to receive weekly administration of either PEG-Loxe 0.2 mg or placebo (1:1 ratio). The randomisation was stratified according to utilisation of sodium-glucose cotransporter 2 inhibitors, history of CV disease and body mass index. The research period is expected to be 3 years, with a 1-year recruitment period and a 2-year follow-up period. The primary outcome is the occurrence of the first MACE, described as CV death, non-fatal myocardial infarction or non-fatal stroke. The statistical analyses were undertaken on the intent-to-treat patient. The primary outcome was evaluated using a Cox proportional hazards model with treatment and randomisation strata as the covariates.
      Ethics and Dissemination: The current research has been authorised by the Ethics Committee of Tianjin Medical University Chu Hsien-I Memorial Hospital (approval number: ZXYJNYYhMEC2022-2). Researchers must acquire informed consent from every participant before conducting any protocol-associated procedures. The findings of this study will be published in a peer-reviewed journal.
      Trial Registration Number: ChiCTR2200056410.
      Competing Interests: Competing interests: YD is employed by Hansoh Pharma. Other authors declare no competing interests.
      (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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    • Contributed Indexing:
      Keywords: Clinical trials; Diabetic nephropathy & vascular disease; Myocardial infarction; Stroke
    • Molecular Sequence:
      ChiCTR ChiCTR2200056410
    • Accession Number:
      0 (polyethylene glycol loxenatide)
      0 (Peptides)
      3WJQ0SDW1A (Polyethylene Glycols)
      0 (Hypoglycemic Agents)
    • Publication Date:
      Date Created: 20230516 Date Completed: 20230518 Latest Revision: 20230526
    • Publication Date:
      20231215
    • Accession Number:
      PMC10193081
    • Accession Number:
      10.1136/bmjopen-2022-069080
    • Accession Number:
      37192802