Type 2 DiabetesPhase 4NCT07747402
Insulin Icodec Initiation Strategies and Day-4 Supplemental Dosing in Type 2 Diabetes
A Phase 4 study testing Insulin icodec in people with Type 2 Diabetes, run by Xi'an International Medical Center Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Insulin icodec
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 462 participants
- Where
- 1 siteChina
- Study dates
- Jan 2027to Mar 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Xi'an International Medical Center Hospital
Xi'an, Shaanxi, 710100
Tao Liu, 86-29-68301145, neifenmi@163.com
Tao Liu
About this study
Official title: Effects of Different Insulin Icodec Initiation Strategies and a Day-4 Supplemental Dosing Decision on Early Fasting Blood Glucose Target Attainment in Type 2 Diabetes: A Multicenter, Randomized, Open-Label, 3x2 Factorial Trial
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?
Read more
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
Read the detailed description
Background and rationale: Once-weekly insulin icodec has a half-life of approximately 196 hours, so its pharmacokinetic steady state is not reached until 3 to 4 weeks after initiation. This creates a mismatch with the clinical need to assess and achieve early fasting blood glucose (FBG) control within the first week. The glucose-lowering effect of icodec peaks on days 2 to 3 and remains near-maximal on day 4, offering an early time point to identify patients at risk of not reaching target. However, no prospective trial has compared icodec initiation strategies for early glycemic control or validated an early marker to guide supplemental dosing. This trial addresses that gap.
Design: This is a multicenter, randomized, open-label trial with a 3-by-2 factorial structure. Insulin-naive adults with type 2 diabetes who have not received insulin in the past 3 months are randomized 1:1:1 (stratified by center and baseline FBG) to one of three icodec initiation strategies: a fixed dose of 70 units per week; a dose based on fasting blood glucose (FBG in mmol/L multiplied by 7); or a dose based on body weight (body weight in kg multiplied by 0.15, then by 7). Within each initiation arm, participants are further randomized 1:1 to one of two day-4 management groups. In Group A, FBG is measured on day 4; if FBG is at or above 6.8 mmol/L, a one-time supplemental dose equal to 50% of the starting dose is given that day. In Group B, FBG is measured on day 4 but no supplemental dose is given. Because day-4 management is randomized independently of the day-4 FBG value, the comparison remains a valid randomized comparison.
Treatment and titration: Icodec is injected once weekly, on a fixed weekday, between 6:00 and 9:00 in the morning, in addition to the participant's existing non-insulin glucose-lowering therapy. The first injection defines study Day 1. From Day 15 (for participants who received a day-4 supplemental dose, whose Day 8 dose returns to the original starting dose) or from Day 8 (for those who did not), a standardized weekly titration algorithm adapted from the ONWARDS program is applied through Week 12. A blinded continuous glucose monitor is worn during the first 2 weeks and the last 2 weeks; it is not used for real-time titration decisions.
Primary endpoints: This trial has two independent co-primary endpoints, each tested at a two-sided alpha of 0.05 without alpha splitting across objectives. The first is the proportion of participants achieving target FBG (4.4 to 7.0 mmol/L) at the end of Week 1 (Day 8, before the second injection), compared across the three initiation strategies, with Bonferroni correction for the three pairwise comparisons. The second is the effectiveness of the day-4 threshold-based supplemental dosing rule, evaluated by comparing target attainment between the pooled Group A and Group B.
Follow-up: The randomized treatment period lasts 12 weeks, followed by a 5-week safety follow-up (Weeks 13 to 17) to capture delayed hypoglycemia after the last dose, given the prolonged action of icodec.
- Conditions
- Type 2 Diabetes
- Being tested
- Insulin icodec
- 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
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin icodecDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Insulin icodec |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Day 8 (end of Week 1)
Secondary outcomes (14)
Absolute reduction in fasting blood glucose from baseline at the end of Week 1
The absolute change in fasting blood glucose (mmol/L) from baseline to Day 8, compared among the three initiation strategies.
Measured: Baseline and Day 8
Percentage reduction in fasting blood glucose from baseline at the end of Week 1
The percentage change in fasting blood glucose from baseline to Day 8, compared among the three initiation strategies.
Measured: Baseline and Day 8
Safe target attainment rate at the end of Week 1
The proportion of participants with fasting blood glucose within 4.4 to 7.0 mmol/L on the morning of Day 8 and without any level 2 (below 3.0 mmol/L) or level 3 hypoglycemia during Week 1.
Measured: Day 8 (end of Week 1)
Fasting blood glucose target attainment rate at Week 12
The proportion of participants with fasting blood glucose within 4.4 to 7.0 mmol/L at the end of Week 12.
Measured: Week 12
Sustained fasting blood glucose target attainment rate
The proportion of participants whose fasting blood glucose remains within 4.4 to 7.0 mmol/L at every weekly assessment from the end of Week 1 through Week 12.
Measured: From Week 1 through Week 12
Discriminative ability of Day-4 fasting blood glucose for Week-1 target attainment
The discriminative ability of Day-4 fasting blood glucose (cutoff 6.8 mmol/L) for predicting fasting blood glucose target attainment at the end of Week 1, assessed by area under the ROC curve, sensitivity, and specificity, to prospectively test the reproducibility of the early-warning finding from the previous retrospective study.
Time Frame: Day 4 and Day 8
Measured: Day 4 and Day 8
Effectiveness of the 50% supplemental dose on target attainment in participants above the Day-4 threshold
Among participants with Day-4 fasting blood glucose at or above 6.8 mmol/L, the effect of a one-time supplemental dose equal to 50% of the starting dose on fasting blood glucose target attainment at the end of Week 1, compared between Group A and Group B.
Measured: Day 8 (end of Week 1)
Incidence and event rate of hypoglycemia by severity level
The proportion of participants with hypoglycemia and the number of events per exposure, by capillary glucose using ADA levels (level 1 below 3.9 mmol/L, level 2 below 3.0 mmol/L, level 3 requiring assistance), across treatment.
Measured: From Day 1 through Week 17 (including the 5-week safety follow-up)
Incidence and event rate of nocturnal hypoglycemia
The proportion of participants with nocturnal hypoglycemia (00:00 to 06:00) and the number of events per exposure.
Measured: From Day 1 through Week 17 (including the 5-week safety follow-up)
Time in range measured by blinded continuous glucose monitoring
Percentage of time with glucose in the target range of 4.4 to 10.0 mmol/L, measured by blinded continuous glucose monitoring during the first 2 weeks and the last 2 weeks.
Measured: Weeks 1-2 and Weeks 11-12
Time below range measured by blinded continuous glucose monitoring
Percentage of time with glucose below 4.4 mmol/L, measured by blinded continuous glucose monitoring during the first 2 weeks and the last 2 weeks.
Measured: Weeks 1-2 and Weeks 11-12
Time above range measured by blinded continuous glucose monitoring
Percentage of time with glucose above 10.0 mmol/L, measured by blinded continuous glucose monitoring during the first 2 weeks and the last 2 weeks.
Measured: Weeks 1-2 and Weeks 11-12
Glycemic variability measured by blinded continuous glucose monitoring
Glycemic variability assessed as coefficient of variation and standard deviation, measured by blinded continuous glucose monitoring during the first 2 weeks and the last 2 weeks.
Measured: Weeks 1-2 and Weeks 11-12
Change in HbA1c from baseline at Week 12
The change in HbA1c from baseline to the end of Week 12.
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2026
- Study startJan 2027 (estimated)
- Primary completionOct 2027 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 462 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xi'an International Medical Center Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Qiuhe Ji, Principal investigator, Xi'an International Medical Center Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07747402
- Sponsor's protocol ID
- IIT-2026-NFM-01
- Status last verified
- Jul 2026
- First submitted
- 30 Jul 2026
- Last updated
- 5 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying the published results will be made available to qualified researchers whose proposed use has been approved. Data will be shared after appropriate agreements are in place to protect participant confidentiality.
Publications
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.
PubMed 37748181Lingvay 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.
PubMed 37354562Rosenstock 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.
PubMed 37356066Philis-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.
PubMed 36106652Nishimura 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.
PubMed 34413118
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Different Insulin Icodec Initiation Strategies and a Day-4 Supplemental Dosing Decision on Early Fasting Blood Glucose Target Attainment in Type 2 Diabetes: A Multicenter, Randomized, Open-Label, 3x2 Factorial Trial
- ClinicalTrials.gov ID
- NCT07747402
- Acronym / sponsor ID
- IIT-2026-NFM-01
- Conditions
- Type 2 Diabetes
- Keywords
- Insulin icodec, Once-weekly insulin, Basal insulin, Insulin initiation, Fasting blood glucose, Glycemic target attainment, Supplemental dosing, Factorial trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 462 participants (estimated)
- Lead sponsor
- Xi'an International Medical Center HospitalUniversity, hospital or other
- Study start
- Jan 2027 (estimated)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 5 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Background and rationale: Once-weekly insulin icodec has a half-life of approximately 196 hours, so its pharmacokinetic steady state is not reached until 3 to 4 weeks after initiation. This creates a mismatch with the clinical need to assess and achieve early fasting blood glucose (FBG) control within the first week. The glucose-lowering effect of icodec peaks on days 2 to 3 and remains near-maximal on day 4, offering an early time point to identify patients at risk of not reaching target. However, no prospective trial has compared icodec initiation strategies for early glycemic control or validated an early marker to guide supplemental dosing. This trial addresses that gap.
Design: This is a multicenter, randomized, open-label trial with a 3-by-2 factorial structure. Insulin-naive adults with type 2 diabetes who have not received insulin in the past 3 months are randomized 1:1:1 (stratified by center and baseline FBG) to one of three icodec initiation strategies: a fixed dose of 70 units per week; a dose based on fasting blood glucose (FBG in mmol/L multiplied by 7); or a dose based on body weight (body weight in kg multiplied by 0.15, then by 7). Within each initiation arm, participants are further randomized 1:1 to one of two day-4 management groups. In Group A, FBG is measured on day 4; if FBG is at or above 6.8 mmol/L, a one-time supplemental dose equal to 50% of the starting dose is given that day. In Group B, FBG is measured on day 4 but no supplemental dose is given. Because day-4 management is randomized independently of the day-4 FBG value, the comparison remains a valid randomized comparison.
Treatment and titration: Icodec is injected once weekly, on a fixed weekday, between 6:00 and 9:00 in the morning, in addition to the participant's existing non-insulin glucose-lowering therapy. The first injection defines study Day 1. From Day 15 (for participants who received a day-4 supplemental dose, whose Day 8 dose returns to the original starting dose) or from Day 8 (for those who did not), a standardized weekly titration algorithm adapted from the ONWARDS program is applied through Week 12. A blinded continuous glucose monitor is worn during the first 2 weeks and the last 2 weeks; it is not used for real-time titration decisions.
Primary endpoints: This trial has two independent co-primary endpoints, each tested at a two-sided alpha of 0.05 without alpha splitting across objectives. The first is the proportion of participants achieving target FBG (4.4 to 7.0 mmol/L) at the end of Week 1 (Day 8, before the second injection), compared across the three initiation strategies, with Bonferroni correction for the three pairwise comparisons. The second is the effectiveness of the day-4 threshold-based supplemental dosing rule, evaluated by comparing target attainment between the pooled Group A and Group B.
Follow-up: The randomized treatment period lasts 12 weeks, followed by a 5-week safety follow-up (Weeks 13 to 17) to capture delayed hypoglycemia after the last dose, given the prolonged action of icodec.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Fixed 70 U/Week + Day-4 Supplement (Group A) | Active comparator | Drug: Insulin icodecInsulin 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. |
| Fixed 70 U/Week + No Day-4 Supplement (Group B) | Active comparator | Drug: Insulin icodecInsulin 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. |
| FBG-Based Dose (FBG×7) + Day-4 Supplement (Group A) | Experimental | Drug: Insulin icodecInsulin 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. |
| FBG-Based Dose (FBG×7) + No Day-4 Supplement (Group B) | Experimental | Drug: Insulin icodecInsulin 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. |
| Weight-Based Dose (BW×0.15×7) + Day-4 Supplement (Group A) | Experimental | Drug: Insulin icodecInsulin 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. |
| Weight-Based Dose (BW×0.15×7) + No Day-4 Supplement (Group B) | Experimental | Drug: Insulin icodecInsulin 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Insulin icodecOnce-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. | Drug | 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) |
Primary outcome
Proportion of participants achieving target fasting blood glucose (4.4 to 7.0 mmol/L) at the end of Week 1
Time frame: Day 8 (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.
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)
Time frame: Day 8 (end of Week 1)
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.
14 secondary outcomes
Absolute reduction in fasting blood glucose from baseline at the end of Week 1
Time frame: Baseline and Day 8
Percentage reduction in fasting blood glucose from baseline at the end of Week 1
Time frame: Baseline and Day 8
Safe target attainment rate at the end of Week 1
Time frame: Day 8 (end of Week 1)
Fasting blood glucose target attainment rate at Week 12
Time frame: Week 12
Sustained fasting blood glucose target attainment rate
Time frame: From Week 1 through Week 12
Discriminative ability of Day-4 fasting blood glucose for Week-1 target attainment
Time frame: Day 4 and Day 8
Effectiveness of the 50% supplemental dose on target attainment in participants above the Day-4 threshold
Time frame: Day 8 (end of Week 1)
Incidence and event rate of hypoglycemia by severity level
Time frame: From Day 1 through Week 17 (including the 5-week safety follow-up)
Incidence and event rate of nocturnal hypoglycemia
Time frame: From Day 1 through Week 17 (including the 5-week safety follow-up)
Time in range measured by blinded continuous glucose monitoring
Time frame: Weeks 1-2 and Weeks 11-12
Time below range measured by blinded continuous glucose monitoring
Time frame: Weeks 1-2 and Weeks 11-12
Time above range measured by blinded continuous glucose monitoring
Time frame: Weeks 1-2 and Weeks 11-12
Glycemic variability measured by blinded continuous glucose monitoring
Time frame: Weeks 1-2 and Weeks 11-12
Change in HbA1c from baseline at Week 12
Time frame: Baseline and Week 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2026.
- Background: PubMed 37748181Bajaj 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.
- Background: PubMed 37354562Lingvay 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.
- Background: PubMed 37356066Rosenstock 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.
- Background: PubMed 36106652Philis-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.
- Background: PubMed 34413118Nishimura 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.
- Individual participant dataSharing planned: Yes. De-identified individual participant data underlying the published results will be made available to qualified researchers whose proposed use has been approved. Data will be shared after appropriate agreements are in place to protect participant confidentiality.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Qiuhe Ji principal investigator
Xi'an International Medical Center Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Insulin icodec in people with Type 2 Diabetes, run by Xi'an International Medical Center Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 5 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tao Liu (86-29-68301145, neifenmi@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants achieving target fasting blood glucose (4.4 to 7.0 mmol/L) at the end of Week 1 (time frame: Day 8 (end of Week 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07747402, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2026.