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Original Research
26 September 2023

Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5): A Randomized Trial

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Authors: Harpreet S. Bajaj, MD, MPH https://orcid.org/0000-0002-1461-1465, Jens Aberle, MD https://orcid.org/0000-0002-9360-9442, Melanie Davies, MBChB, MD https://orcid.org/0000-0002-9987-9371, Anders Meller Donatsky, MD, PhD https://orcid.org/0000-0002-8549-4171, Marie Frederiksen, MSc, Dilek G. Yavuz, MD https://orcid.org/0000-0002-0075-6313, Amoolya Gowda, MD https://orcid.org/0000-0002-7954-2747, Ildiko Lingvay, MD, MPH, MSCS https://orcid.org/0000-0001-7006-7401, and Bruce Bode, MD https://orcid.org/0000-0002-9998-055XAuthor, Article, & Disclosure Information
Publication: Annals of Internal Medicine
Volume 176, Number 11
https://doi.org/10.7326/M23-1288
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Visual Abstract. Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5) Once-weekly insulin icodec (icodec), a basal insulin analogue that is currently in development, is intended to reduce treatment burden in patients with type 2 diabetes. This randomized trial sought to compare the effectiveness and safety of icodec titrated with a dosing guide app versus once-daily basal insulin analogues dosed per standard practice.
Visual Abstract. Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5)
Once-weekly insulin icodec (icodec), a basal insulin analogue that is currently in development, is intended to reduce treatment burden in patients with type 2 diabetes. This randomized trial sought to compare the effectiveness and safety of icodec titrated with a dosing guide app versus once-daily basal insulin analogues dosed per standard practice.

Abstract

Background:

Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden.

Objective:

To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice.

Design:

52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626)

Setting:

176 sites in 7 countries.

Participants:

1085 insulin-naive adults with T2D.

Intervention:

Icodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300).

Measurements:

The primary outcome was change in glycated hemoglobin (HbA1c) level from baseline to week 52. Secondary outcomes included patient-reported outcomes (Treatment Related Impact Measure for Diabetes [TRIM-D] compliance domain score and change in Diabetes Treatment Satisfaction Questionnaire [DTSQ] total treatment satisfaction score).

Results:

The estimated mean change in HbA1c level from baseline to week 52 was greater with icodec with app than with OD analogues, with noninferiority (P < 0.001) and superiority (P = 0.009) confirmed in prespecified hierarchical testing (estimated treatment difference [ETD], −0.38 percentage points [95% CI, −0.66 to −0.09 percentage points]). At week 52, patient-reported outcomes were more favorable with icodec with app than with OD analogues (ETDs, 3.04 [CI, 1.28 to 4.81] for TRIM-D and 0.78 [CI, 0.10 to 1.47] for DTSQ). Rates of clinically significant or severe hypoglycemia were low and similar with both treatments.

Limitation:

Inability to differentiate the effects of icodec and the dosing guide app.

Conclusion:

Compared with OD analogues, icodec with app showed superior HbA1c reduction and improved treatment satisfaction and compliance with similarly low hypoglycemia rates.

Primary Funding Source:

Novo Nordisk A/S.

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Supplemental Material

References

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 176 • Number 11 • November 2023
Pages: 1476 - 1485

History

Published online: 26 September 2023
Published in issue: November 2023

Keywords

  1. Adverse events
  2. Clinical trials
  3. Confidence intervals
  4. HbA1c
  5. Hypoglycemia
  6. Hypoglycemics
  7. Insulin
  8. Randomized trials
  9. Safety
  10. Treatment guidelines

Copyright

© 2023 American College of Physicians.

Authors

Affiliations

Harpreet S. Bajaj, MD, MPH https://orcid.org/0000-0002-1461-1465
LMC Diabetes and Endocrinology, Brampton, Ontario, Canada (H.S.B.)
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Jens Aberle, MD https://orcid.org/0000-0002-9360-9442
University Medical Center Hamburg-Eppendorf, Hamburg, Germany (J.A.)
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Melanie Davies, MBChB, MD https://orcid.org/0000-0002-9987-9371
Diabetes Research Centre, University of Leicester, and Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, United Kingdom (M.D.)
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Anders Meller Donatsky, MD, PhD https://orcid.org/0000-0002-8549-4171
Novo Nordisk A/S, Søborg, Denmark (A.M.D., M.F., A.G.)
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Marie Frederiksen, MSc
Novo Nordisk A/S, Søborg, Denmark (A.M.D., M.F., A.G.)
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Dilek G. Yavuz, MD https://orcid.org/0000-0002-0075-6313
Department of Endocrinology and Metabolism, Marmara University School of Medicine, Istanbul, Turkey (D.G.Y.)
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Amoolya Gowda, MD https://orcid.org/0000-0002-7954-2747
Novo Nordisk A/S, Søborg, Denmark (A.M.D., M.F., A.G.)
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Ildiko Lingvay, MD, MPH, MSCS https://orcid.org/0000-0001-7006-7401
Division of Endocrinology, Department of Internal Medicine and Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, Texas (I.L.)
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Bruce Bode, MD https://orcid.org/0000-0002-9998-055X
Atlanta Diabetes Associates, Atlanta, Georgia (B.B.).
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Acknowledgment: The authors thank all of the trial participants, investigators, and trial site staff. A medical writer (Jen Geatrell, PhD, of Oxford PharmaGenesis, Oxford, United Kingdom) who was funded by Novo Nordisk assisted with drafting of the manuscript under the direction of the authors.
Financial Support: By Novo Nordisk A/S.
Data Sharing Statement: Individual participant data will be shared in data sets in a deidentified/anonymized format. Shared data will include data sets from clinical research sponsored by Novo Nordisk that was completed after 2001 for product indications approved in both the European Union and the United States. The study protocol and the redacted clinical study report will be made available according to Novo Nordisk data sharing commitments. These data will be available permanently after research completion and approval of product and product use in both the European Union and the United States (no end date). Data will be shared with bona fide researchers who submit a research proposal requesting access to data for use as approved by the Independent Review Board according to its charter (see www.novonordisk-trials.com). These data can be accessed via an access request proposal form; the access criteria can be found at www.novonordisk-trials.com. The data will be made available on a specialized SAS data platform.
Corresponding Author: Harpreet S. Bajaj, MD, MPH, LMC Diabetes and Endocrinology, 2979 Bovaird Drive East, Brampton, ON L6S 0C6, Canada; e-mail, [email protected].
Correction: This article was amended on 7 November 2023 to correct an error in Figure 2. A correction has been published (doi:10.7326/L23-0410). This article was amended on 12 December 2023 to correct a typographical error in panel E of Figure 2.
Author Contributions: Conception and design: H.S. Bajaj, A.M. Donatsky, A. Gowda.
Analysis and interpretation of the data: H.S. Bajaj, J. Aberle, M. Davies, A.M. Donatsky, M. Frederiksen, A. Gowda, I. Lingvay, B. Bode.
Drafting of the article: H.S. Bajaj, A.M. Donatsky, M. Frederiksen, A. Gowda.
Critical revision for important intellectual content: H.S. Bajaj, J. Aberle, M. Davies, A.M. Donatsky, M. Frederiksen, D.G. Yavuz, A. Gowda, I. Lingvay, B. Bode.
Final approval of the article: H.S. Bajaj, J. Aberle, M. Davies, A.M. Donatsky, M. Frederiksen, D.G. Yavuz, A. Gowda, I. Lingvay, B. Bode.
Provision of study materials or patients: H.S. Bajaj, I. Lingvay.
Statistical expertise: H.S. Bajaj, A.M. Donatsky, M. Frederiksen.
Administrative, technical, or logistic support: A.M. Donatsky.
Collection and assembly of data: H.S. Bajaj, A.M. Donatsky, D.G. Yavuz, A. Gowda, I. Lingvay, B. Bode.
This article was published at Annals.org on 26 September 2023.

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Harpreet S. Bajaj, Jens Aberle, Melanie Davies, et al. Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5): A Randomized Trial. Ann Intern Med.2023;176:1476-1485. [Epub 26 September 2023]. doi:10.7326/M23-1288

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