Insulin Icodec Initiation Strategies and Day-4 Supplemental Dosing in Type 2 Diabetes

NCT07747402 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: IIT-2026-NFM-01
• Study Type: interventional
• Target: 462
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to find the best way to start once-weekly insulin icodec in adults with type 2 diabetes who have not used insulin in the past 3 months, so that their fasting blood glucose reaches the target range within the first week. The main questions it aims to answer are:

• Which of three starting-dose methods brings the most people to their fasting blood glucose target by the end of the first week?
• On day 4 after starting, if fasting blood glucose is still high, does giving one extra half-dose of insulin help more people reach target safely? Participants will be randomly placed into one of three starting-dose groups: a fixed weekly dose, a dose based on their fasting blood glucose, or a dose based on their body weight. Within each group, participants will also be randomly assigned either to receive an extra insulin dose on day 4 if their fasting blood glucose is at or above a set level, or to receive no extra dose. Participants will:
• Start once-weekly insulin icodec and continue their current non-insulin diabetes medicines
• Check their fasting blood glucose, including on day 4 after starting
• Wear a blinded continuous glucose monitor during the first 2 weeks and the last 2 weeks
• Attend weekly visits for dose adjustment and safety checks over 12 weeks, followed by a 5-week safety follow-up

Conditions

Type 2 Diabetes

Keywords

Insulin icodec; Once-weekly insulin; Basal insulin; Insulin initiation; Fasting blood glucose; Glycemic target attainment; Supplemental dosing; Factorial trial; Continuous glucose monitoring; Diabetes management

Outcome Measures

Primary Outcomes (2)

• Proportion of participants achieving target fasting blood glucose (4.4 to 7.0 mmol/L) at the end of Week 1

  The proportion of participants whose fasting blood glucose is within the target range of 4.4 to 7.0 mmol/L, measured on the morning of Day 8 before the second weekly injection and any dose adjustment. This endpoint is compared among the three insulin icodec initiation strategies (fixed 70 U/week, FBGx7, and BWx0.15x7) to identify the strategy that best promotes early target attainment. Fasting blood glucose is assessed by capillary measurement.

  Day 8 (end of Week 1)

• Proportion of participants achieving target fasting blood glucose (4.4 to 7.0 mmol/L) at the end of Week 1, compared between the day-4 supplemental dosing decision groups (Group A vs Group B)

  The effectiveness of the day-4 threshold-based supplemental dosing rule, evaluated as the proportion of participants achieving target fasting blood glucose (4.4 to 7.0 mmol/L) on the morning of Day 8. All three initiation arms are pooled, and Group A (fasting blood glucose measured on Day 4; a one-time supplemental dose equal to 50% of the starting dose given if the value is at or above 6.8 mmol/L) is compared with Group B (fasting blood glucose measured on Day 4 but no supplemental dose given). Fasting blood glucose is assessed by capillary measurement.

  Day 8 (end of Week 1)

Secondary Outcomes (14)

• Absolute reduction in fasting blood glucose from baseline at the end of Week 1

  Baseline and Day 8

• Percentage reduction in fasting blood glucose from baseline at the end of Week 1

  Baseline and Day 8

• Safe target attainment rate at the end of Week 1

  Day 8 (end of Week 1)

• Fasting blood glucose target attainment rate at Week 12

  Week 12

• Sustained fasting blood glucose target attainment rate

  From Week 1 through Week 12

Other Outcomes (6)

• Time to first fasting blood glucose target attainment

  From Day 1 through Week 12

• Stability of fasting blood glucose target attainment after first reaching target

  From first target attainment through Week 12

• Proportion of participants triggering Day-4 supplemental dosing

  Day 4

Study Arms (6)

Fixed 70 U/Week + Day-4 Supplement (Group A)

ACTIVE COMPARATOR

Insulin icodec is initiated at a fixed dose of 70 units once weekly, injected subcutaneously on a fixed weekday between 6:00 and 9:00 in the morning, added to existing non-insulin glucose-lowering therapy. On day 4, fasting blood glucose is measured; if it is at or above 6.8 mmol/L, a one-time supplemental dose equal to 50% of the starting dose (35 units) is given that day. For participants who received the supplemental dose, the day 8 dose returns to the starting dose, and a standardized weekly titration algorithm is applied from day 15 through Week 12.

Drug: Insulin icodec

Fixed 70 U/Week + No Day-4 Supplement (Group B)

ACTIVE COMPARATOR

Insulin icodec is initiated at a fixed dose of 70 units once weekly, injected subcutaneously on a fixed weekday between 6:00 and 9:00 in the morning, added to existing non-insulin glucose-lowering therapy. On day 4, fasting blood glucose is measured for recording only; no supplemental dose is given. A standardized weekly titration algorithm is applied from day 8 through Week 12.

Drug: Insulin icodec

FBG-Based Dose (FBG×7) + Day-4 Supplement (Group A)

EXPERIMENTAL

Insulin icodec is initiated at a dose calculated as fasting blood glucose (mmol/L) multiplied by 7, given once weekly, injected subcutaneously on a fixed weekday between 6:00 and 9:00 in the morning, added to existing non-insulin glucose-lowering therapy. On day 4, fasting blood glucose is measured; if it is at or above 6.8 mmol/L, a one-time supplemental dose equal to 50% of the starting dose is given that day. For participants who received the supplemental dose, the day 8 dose returns to the starting dose, and a standardized weekly titration algorithm is applied from day 15 through Week 12.

Drug: Insulin icodec

FBG-Based Dose (FBG×7) + No Day-4 Supplement (Group B)

EXPERIMENTAL

Insulin icodec is initiated at a dose calculated as fasting blood glucose (mmol/L) multiplied by 7, given once weekly, injected subcutaneously on a fixed weekday between 6:00 and 9:00 in the morning, added to existing non-insulin glucose-lowering therapy. On day 4, fasting blood glucose is measured for recording only; no supplemental dose is given. A standardized weekly titration algorithm is applied from day 8 through Week 12.

Drug: Insulin icodec

Weight-Based Dose (BW×0.15×7) + Day-4 Supplement (Group A)

EXPERIMENTAL

Insulin icodec is initiated at a dose calculated as body weight (kg) multiplied by 0.15 and then by 7, given once weekly, injected subcutaneously on a fixed weekday between 6:00 and 9:00 in the morning, added to existing non-insulin glucose-lowering therapy. On day 4, fasting blood glucose is measured; if it is at or above 6.8 mmol/L, a one-time supplemental dose equal to 50% of the starting dose is given that day. For participants who received the supplemental dose, the day 8 dose returns to the starting dose, and a standardized weekly titration algorithm is applied from day 15 through Week 12.

Drug: Insulin icodec

Weight-Based Dose (BW×0.15×7) + No Day-4 Supplement (Group B)

EXPERIMENTAL

Insulin icodec is initiated at a dose calculated as body weight (kg) multiplied by 0.15 and then by 7, given once weekly, injected subcutaneously on a fixed weekday between 6:00 and 9:00 in the morning, added to existing non-insulin glucose-lowering therapy. On day 4, fasting blood glucose is measured for recording only; no supplemental dose is given. A standardized weekly titration algorithm is applied from day 8 through Week 12.

Drug: Insulin icodec

Interventions

Insulin icodec DRUG

Once-weekly subcutaneous insulin icodec, injected on a fixed weekday between 6:00 and 9:00 in the morning, added to existing non-insulin glucose-lowering therapy. The starting dose is determined by the assigned initiation strategy: a fixed 70 units per week; fasting blood glucose (mmol/L) multiplied by 7; or body weight (kg) multiplied by 0.15 and then by 7. On day 4, participants in Group A with fasting blood glucose at or above 6.8 mmol/L receive a one-time supplemental dose equal to 50% of the starting dose, while Group B receives no supplemental dose. A standardized weekly titration algorithm is applied through Week 12.

FBG-Based Dose (FBG×7) + Day-4 Supplement (Group A); FBG-Based Dose (FBG×7) + No Day-4 Supplement (Group B); Fixed 70 U/Week + Day-4 Supplement (Group A); Fixed 70 U/Week + No Day-4 Supplement (Group B); Weight-Based Dose (BW×0.15×7) + Day-4 Supplement (Group A); Weight-Based Dose (BW×0.15×7) + No Day-4 Supplement (Group B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Diagnosis of type 2 diabetes mellitus for at least 180 days
• No insulin treatment of any kind within the past 3 months
• Currently treated with at least one non-insulin glucose-lowering agent (oral agent or GLP-1 receptor agonist) with inadequate glycemic control, and a clinical indication to start basal insulin
• HbA1c of 7.0% to 11.0% at screening
• Body mass index of 35.0 kg/m2 or lower
• Able and willing to wear a continuous glucose monitor per protocol, to undergo day-4 fasting blood glucose assessment, and to attend all scheduled visits
• Provides written informed consent

You may not qualify if:

• Type 1 diabetes, specific types of diabetes, or recent acute complications such as diabetic ketoacidosis or hyperosmolar hyperglycemic state
• Level 2 or level 3 hypoglycemia within the past 3 months, or hypoglycemia unawareness
• Current use, or use within the past 3 months, of systemic glucocorticoids (excluding inhaled or topical preparations) or other agents that markedly affect blood glucose
• Moderate to severe renal impairment (eGFR below 45 mL/min/1.73 m2 by the CKD-EPI 2021 creatinine equation) or need for dialysis
• Active liver disease, abnormal liver function (ALT or AST above 3 times the upper limit of normal), or decompensated cirrhosis
• Marked edema, large-volume ascites, amputation, or other conditions that may impair accurate body weight measurement or distort weight-based dosing
• Known allergy to insulin icodec or its excipients
• Extensive skin lesions, allergy to continuous glucose monitor adhesive, or anticipated frequent magnetic resonance imaging that may interfere with monitor wear or interpretation
• Active malignancy
• Acute cardiovascular or cerebrovascular event (such as myocardial infarction, stroke, or unstable angina) within the past 6 months, or other major illness with short expected survival or poor compliance
• Pregnancy or lactation, or women of childbearing potential with pregnancy plans
• Participation in another drug or device clinical trial within the past 3 months
• Other conditions judged by the investigator to be unsuitable for enrollment or likely to affect participant safety or data reliability

Sponsors & Collaborators

• Xi'an International Medical Center Hospital: lead

Study Sites (1)

Xi'an International Medical Center Hospital

Xi'an, Shaanxi, 710100, China

Location

Related Publications (5)

• Bajaj HS, Aberle J, Davies M, Donatsky AM, Frederiksen M, Yavuz DG, Gowda A, Lingvay I, Bode B. 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.

  PMID: 37748181 BACKGROUND

• Lingvay I, Asong M, Desouza C, Gourdy P, Kar S, Vianna A, Vilsboll T, Vinther S, Mu Y. Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial. JAMA. 2023 Jul 18;330(3):228-237. doi: 10.1001/jama.2023.11313.

  PMID: 37354562 BACKGROUND

• Rosenstock J, Bain SC, Gowda A, Jodar E, Liang B, Lingvay I, Nishida T, Trevisan R, Mosenzon O; ONWARDS 1 Trial Investigators. Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin. N Engl J Med. 2023 Jul 27;389(4):297-308. doi: 10.1056/NEJMoa2303208. Epub 2023 Jun 24.

  PMID: 37356066 BACKGROUND

• Philis-Tsimikas A, Bajaj HS, Begtrup K, Cailleteau R, Gowda A, Lingvay I, Mathieu C, Russell-Jones D, Rosenstock J. Rationale and design of the phase 3a development programme (ONWARDS 1-6 trials) investigating once-weekly insulin icodec in diabetes. Diabetes Obes Metab. 2023 Feb;25(2):331-341. doi: 10.1111/dom.14871. Epub 2022 Oct 14.

  PMID: 36106652 BACKGROUND

• Nishimura E, Pridal L, Glendorf T, Hansen BF, Hubalek F, Kjeldsen T, Kristensen NR, Lutzen A, Lyby K, Madsen P, Pedersen TA, Ribel-Madsen R, Stidsen CE, Haahr H. Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing. BMJ Open Diabetes Res Care. 2021 Aug;9(1):e002301. doi: 10.1136/bmjdrc-2021-002301.

  PMID: 34413118 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

insulin icodec

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Qiuhe Ji

  Xi'an International Medical Center Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tao Liu

CONTACT

86-29-68301145; neifenmi@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2026
• First Posted: August 5, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: August 5, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 6 months after publication of the primary results and ending 5 years thereafter.
• Access Criteria: Requests should be directed to the principal investigator. Data will be shared with researchers who provide a methodologically sound proposal and sign a data access agreement.

Locations

CN (1)