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Efficacy and Safety of Basal Insulin-Based Treatment Versus Twice-Daily Premixed Insulin After Short-Term Intensive Insulin Therapy in Patients with Type 2 Diabetes Mellitus in China: Study Protocol for a Randomized Controlled Trial (BEYOND V)

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Abstract

Introduction

Many Chinese patients who are uncontrolled by oral antidiabetic drugs (OADs) receive short-term intensive insulin therapy (IIT) in hospital to rapidly relieve glucose-associated toxicity and to preserve/improve β-cell function. However, evidence for optimizing insulin algorithms for maintenance treatment after IIT is lacking. This study will compare the efficacy and safety of basal insulin-based treatment versus twice-daily premixed insulin in type 2 diabetes mellitus (T2DM) patients after short-term in-hospital IIT.

Methods

This 26-week randomized, multicenter, positive-controlled, open-label, parallel-group study will enroll approximately 400 male and female patients aged 18–70 years with poorly-controlled T2DM (HbA1c > 7.5%) despite treatment with metformin plus at least one other OAD for 8 or more weeks. During a run-in period of 7–10 days, patients will be treated in-hospital with IIT comprising insulin glargine (Lantus®) once daily and insulin glulisine (Apidra®) three times daily; both regimens will be titrated daily to achieve the glycemic goal. Eligible patients will then be randomized in a 1:1 ratio to insulin glargine plus OADs or twice-daily premixed insulin (NovoLog® Mix 70/30) for 24 weeks, with metformin maintained throughout the study in both treatment groups. The primary endpoint is HbA1c change from baseline to week 24. Secondary endpoints include assessment of fasting plasma glucose, total daily insulin dose, hypoglycemia incidence, body weight change, adverse events, and patient satisfaction.

Discussion

Given the current lack of clinical data, this study will provide evidence supporting safe and effective glycemic control using basal insulin glargine-based therapy plus OADs compared with twice-daily premixed insulin in Chinese patients with T2DM after short-term IIT. This will assist physicians by providing a wider choice of treatments.

Trial registration

ClinicalTrials.gov identifier, NCT03359837 (registered on 2 December 2017).

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Acknowledgements

This study is currently recruiting participants.

Funding

The study and the journal’s Rapid Service Fee will be funded by Sanofi, China. The funder has contributed to the design of the study, the development of the study protocol, review and revision of this manuscript, and will contribute to the analysis and interpretation of data. The funder has been involved in the decision to submit this manuscript for publication.

Medical Writing, Editorial, and Other Assistance

Editorial assistance in the preparation of this article was provided by David P. Figgitt PhD, ISMPP CMPP™, Content Ed Net. Support for this assistance was funded by Sanofi, China.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosures

Yiming Mu has received research grants, personal fees or non-financial support from Eli Lilly, Novartis, Novo Nordisk, Merck, Bayer, Sanofi, Roche, Boehringer Ingelheim, and Sanofi. Lixin Guo has received research grants, personal fees or non-financial support from Eli Lilly, Bristol-Myers Squibb, Novartis, Novo Nordisk, Merck, Bayer, Takeda, Sanofi, Roche, and Boehringer Ingelheim. Nan Cui, ** Wang have nothing to disclose.

Compliance with Ethics Guideline

Ethical approval for this study was obtained from the local Institutional Review Board at each study site (Supplementary material). Informed consent to participate in the study will be obtained from all participants. The research will be performed in accordance with the Declaration of Helsinki and the ICH GCP, as well as all applicable laws, rules and regulations.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Author information

Authors and Affiliations

  1. Endocrinology Department, Gansu Provincial People’s Hospital, Lanzhou, China

    **g Liu

  2. Endocrinology Department, Tian** First Center Hospital, Tian**, China

    ** Wang

  3. Medical Affair Department, Sanofi Pharmaceuticals Co., Ltd, Shanghai, China

    Nan Cui, **a Zhang & **gcheng Liu

  4. Endocrinology Department, Chinese PLA General Hospital, Bei**g, China

    Yiming Mu

  5. Endocrinology Department, Bei**g Hospital, Bei**g, China

    Lixin Guo

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  1. **g Liu
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Corresponding authors

Correspondence to Yiming Mu or Lixin Guo.

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Liu, J., Jiang, X., Xu, B. et al. Efficacy and Safety of Basal Insulin-Based Treatment Versus Twice-Daily Premixed Insulin After Short-Term Intensive Insulin Therapy in Patients with Type 2 Diabetes Mellitus in China: Study Protocol for a Randomized Controlled Trial (BEYOND V). Adv Ther 37, 1675–1687 (2020). https://doi.org/10.1007/s12325-020-01265-6

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