A Study Using Flash Glucose Measurements for a New Once-weekly Insulin (Insulin Icodec) in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 9)

• Insulin Icodec (Drug): Participants will receive insulin icodec once-weekly subcutaneously into the thigh, upper arm or abdomen.

Primary outcomes

• Change in Glycosylated Haemoglobin (HbA1c) [Baseline (week 0), week 26]: Change in HbA1c from week 0 to week 26 is presented in percentage-point.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study
* Age above or equal to 18 years at the time of signing informed consent
* Diagnosed with type 2 diabetes (T2D) greater than or equal to (>=) 180 days before screening
* HbA1c from 7.0%-11.0% (53.0-96.7 millimoles per mole \[mmol/mol\]) both inclusive at screening confirmed by central laboratory analysis
* Insulin-naïve. However, short term insulin treatment for a maximum of 14 consecutive days before screening is allowed, as is prior insulin treatment for gestational diabetes
* Stable daily dose(s) >=90 days before screening of any of the following antidiabetic drug(s) or combination regimen(s) at effective or maximum tolerated dose as judged by the investigator:

  1. Any metformin formulations >= 1500 milligrams (mg) or maximum tolerated or effective dose or
  2. Any metformin combination formulations >=1500 mg or maximum tolerated or effective dose or
  3. Other antidiabetic Drugs including combination products (>=half of the maximum approved dose according to local label or maximum tolerated or effective dose) of the classes specified below: Sulfonylureas, Meglitinides (glinides), Dipeptidyl peptidase-4 (DPP-4) inhibitors, Sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors, Thiazolidinedione, Alpha-glucosidase inhibitors, Oral combination products (for the allowed individual oral antidiabetic drugs, Oral or injectable glucagon-like peptide-1 (GLP-1) receptor agonists
* Intensification with basal insulin is indicated to achieve fasting glycaemic target (4.4-7.2 millimoles per liter \[mmol/L\]; 80-130 milligrams per deciliter \[mg/dL\]) at the discretion of the treating investigator
* Body mass index (BMI) less than or equal to (<=) 40.0 kilograms per meter square (kg/m\^2)

Exclusion Criteria:

* Unwilling or unable to avoid concomitant medication e.g., ascorbic acid (vitamin C) that can influence the flash glucose monitoring (FGM) sensor throughout the study and contraindications e.g., implanted medical devices such as pacemakers
* Any episodes of diabetic ketoacidosis within 90 days before screening as declared by the participant or in the medical records
* Myocardial infarction, stroke, transient ischaemic attack or hospitalisation for unstable angina pectoris within 180 days before the day of screening and between screening and initiation visits
* Chronic heart failure classified as being in 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 90 days before the day of screening or in the period between screening and initiation visits. Pharmacological pupil dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination

Participant flow

Outcome results

• Change in Glycosylated Haemoglobin (HbA1c) (Primary), Mean, Percentage-point of HbA1c: Insulin Icodec -1.18 +/- 0.91

Adverse events

Time frame: From week 0 up to week 31

Serious adverse events by term

Other adverse events by term

• Results publication: Bergenstal RM, Asbjornsdottir B, Johanning Bari T, Hulkund S, Winhofer Y, Wysham C. Continuous Glucose Monitoring-Based Titration of Once-Weekly Insulin Icodec in Insulin-Naive Individuals with Type 2 Diabetes (ONWARDS 9): A Phase 3b, Multicenter, Single-Arm, Treat-to-Target Clinical Trial. Diabetes Technol Ther. 2025 Jul;27(7):527-536. doi: 10.1089/dia.2025.0050. Epub 2025 Mar 5. PMID 40040516

• Study Protocol (PDF, 2022-12-09)
• Statistical Analysis Plan (PDF, 2023-02-09)

• Clinical Transparency (dept. 2834), Study director, Novo Nordisk A/S