Once-weekly insulin icodec versus once-daily insulin degludec as part of a basal-bolus regimen in individuals with type 1 diabetes (ONWARDS 6) : a phase 3a, randomised, open-label, treat-to-target trial

Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved..

BACKGROUND: ONWARDS 6 compared the efficacy and safety of once-weekly subcutaneous insulin icodec (icodec) and once-daily insulin degludec (degludec) in adults with type 1 diabetes.

METHODS: This 52-week (26-week main phase plus a 26-week safety extension), randomised, open-label, treat-to-target, phase 3a trial was done at 99 sites across 12 countries. Adults with type 1 diabetes (glycated haemoglobin [HbA1c] <10·0% [86 mmol/mol]) were randomly assigned (1:1) to once-weekly icodec or once-daily degludec, both in combination with insulin aspart (two or more daily injections). The primary endpoint was change in HbA1c from baseline to week 26, tested for non-inferiority (0·3 percentage point margin) in all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04848480, and is now complete.

FINDINGS: Between April 30 and Oct 15, 2021, of 655 participants screened, 582 participants were randomly assigned to icodec (n=290) or degludec (n=292). At week 26, from baseline values of 7·59% (icodec) and 7·63% (degludec), estimated mean changes in HbA1c were -0·47 percentage points and -0·51 percentage points, respectively (estimated treatment difference 0·05 percentage points [95% CI -0·13 to 0·23]), confirming non-inferiority of icodec to degludec (p=0·0065). Overall rate of combined clinically significant or severe hypoglycaemia (baseline to week 26) was statistically significantly higher with icodec than degludec (19·9 vs 10·4 events per patient-year of exposure; estimated rate ratio 1·9 [95% CI 1·5 to 2·3]; p<0·0001). The rate was also statistically significantly higher with icodec than degludec when evaluated over 57 weeks (52 weeks plus a 5-week follow-up period). 39 serious adverse events were reported in 24 (8%) participants receiving icodec, and 25 serious adverse events were reported in 20 (7%) participants receiving degludec. One participant in the icodec group died; this was judged unlikely to be due to the trial product.

INTERPRETATION: In adults with type 1 diabetes, once-weekly icodec showed non-inferiority to once-daily degludec in HbA1c reduction at week 26, with statistically significantly higher rates of combined clinically significant or severe hypoglycaemia. For icodec, time below 3·0 mmol/L (<54 mg/dL) was at the threshold of the internationally recommended target (<1%) during weeks 22-26 and below target during weeks 48-52.

FUNDING: Novo Nordisk.

Errataetall:	CommentIn: Lancet. 2023 Nov 4;402(10413):1598-1599. - PMID 37863082
Medienart:	E-Artikel

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	Zur Gesamtaufnahme - volume:402
Enthalten in:	Lancet (London, England) - 402(2023), 10413 vom: 04. Nov., Seite 1636-1647

Sprache:	Englisch

Beteiligte Personen:	Russell-Jones, David [VerfasserIn] Babazono, Tetsuya [VerfasserIn] Cailleteau, Roman [VerfasserIn] Engberg, Susanne [VerfasserIn] Irace, Concetta [VerfasserIn] Kjaersgaard, Maiken Ina Siegismund [VerfasserIn] Mathieu, Chantal [VerfasserIn] Rosenstock, Julio [VerfasserIn] Woo, Vincent [VerfasserIn] Klonoff, David C [VerfasserIn]

Links:	Volltext

Themen:	54Q18076QB Blood Glucose Clinical Trial, Phase III Hypoglycemic Agents Insulin degludec Insulin icodec Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Anmerkungen:	Date Completed 13.11.2023 Date Revised 13.11.2023 published: Print-Electronic ClinicalTrials.gov: NCT04848480 CommentIn: Lancet. 2023 Nov 4;402(10413):1598-1599. - PMID 37863082 Citation Status MEDLINE

doi:	10.1016/S0140-6736(23)02179-7

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	NLM363554300