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 Nov;176(11):1476-1485. doi: 10.7326/M23-1288. Epub 2023 Sep 26.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose
  • Diabetes Mellitus, Type 2* / drug therapy
  • Humans
  • Hypoglycemia* / drug therapy
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Insulin Glargine / therapeutic use
  • Mobile Applications*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Insulin Glargine
  • insulin icodec

Associated data

  • ClinicalTrials.gov/NCT04760626