Phase 3 N=582 Randomized Treatment

A Research Study to Compare a New Weekly Insulin, Insulin Icodec, and an Available Daily Insulin, Insulin Degludec, Both in Combination With Mealtime Insulin in People With Type 1 Diabetes (ONWARDS 6)

Diabetes Mellitus, Type 1

Bottom Line

View on ClinicalTrials.gov: NCT04848480 ↗

Enrolled (actual)

582

Serious AEs

7.6%

Results posted

Jun 2025

Primary outcome: Primary: Change in Glycosylated Haemoglobin (HbA1c) at Week 26 — -0.47; -0.51 Percentage of HbA1c — p=0.0065

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: insulin icodec (Drug); insulin degludec (Drug); insulin aspart (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Novo Nordisk A/S
Primary completion: Apr 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Glycosylated Haemoglobin (HbA1c) at Week 26	-0.47; -0.51	0.0065 sig
SECONDARY Change in Glycosylated Haemoglobin (HbA1c) at Week 52	-0.37; -0.54	—
SECONDARY Change in Fasting Plasma Glucose (FPG)	-0.84; -1.87	—
SECONDARY Percentage of Time in Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter [mg/dL]) Using Continuous Glucose Monitoring (CGM) System	59.10; 60.85	—
SECONDARY Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction	1.97; 3.06	—
SECONDARY Number of Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26	47; 17	—
SECONDARY Number of Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57	56; 25	—
SECONDARY Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL) Confirmed by Blood Glucose [BG] Meter): From Baseline (Week 0) to Week 26	2789; 1478	—
SECONDARY Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL) Confirmed by BG Meter): From Baseline (Week 0) to Week 57	5047; 2811	—
SECONDARY Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26	2836; 1495	—
SECONDARY Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57	5103; 2836	—
SECONDARY Number of Nocturnal Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26	481; 227	—
SECONDARY Number of Nocturnal Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57	870; 462	—
SECONDARY Percentage of Time Spent Less Than (<) 3.0 mmol/L (54 mg/dL) Using Continuous Glucose Monitoring (CGM) System	1.02; 0.68	—
SECONDARY Percentage of Time Spent Greater Than (>) 10 mmol/L (180 mg/dL) Using Continuous Glucose Monitoring (CGM) System	37.03; 36.25	—
SECONDARY Mean Total Weekly Insulin Dose: From Week 24 to Week 26	310.52; 322.68	—
SECONDARY Mean Total Weekly Insulin Dose: From Week 50 to Week 52	310.14; 328.90	—
SECONDARY Change in Body Weight	1.29; 1.01	—

Summary

This study compares insulin icodec (a new insulin) to insulin degludec (an insulin already available on the market) in people with type 1 diabetes. The study will look at how well insulin icodec taken weekly controls blood sugar compared to insulin degludec taken daily. Participants will either get insulin icodec that participants will have to inject once a week on the same day of the week, or insulin degludec that participants will have to inject once a day at the same time every day. Which treatment participants get is decided at random. Participants will also get a mealtime insulin. The insulin is injected with a needle in a skin fold in the thigh, upper arm or stomach. The study will last for about 1 year and 2 months. Participants will have 28 clinic visits and 28 phone calls with the study doctor. At 11 clinic visits participants will have blood samples taken. At 6 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit. Participants will be asked to wear a sensor that measures your blood sugar all the time. Participants will be asked to wear it for a total of 57 weeks (around 1 year). Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Eligibility Criteria

Inclusion Criteria

Male or female aged greater than or equal to 18 years at the time of signing informed consent.
Diagnosed with type 1 diabetes mellitus greater than or equal to 1 year prior to the day of screening.
Treated with multiple daily insulin injections (basal and bolus insulin analogue regimes) greater than or equal to 1 year prior to the day of screening.
HbA1c below10% at screening visit based on analysis from central laboratory.

Exclusion Criteria

Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
Chronic heart failure classified as New York Heart Association (NYHA) Class IV at screening.
Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).
Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04848480). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.