Diabetes Mellitus, Type 2
Conditions
Brief summary
This study compares insulin icodec to different daily insulins in people with type 2 diabetes. The study will look at how well insulin icodec taken once weekly controls blood sugar compared to the insulins taken once daily. Participants will either get insulin icodec, that participants will have to inject once a week on the same day of the week, or a marketed insulin, that participants will have to inject once a day. Which treatment participants get is decided at random. The insulin is injected with a needle in a skin fold in the thigh, upper arm or stomach. Participants will measure their blood sugar every day. Participants will get a study phone to record safety data in the electronic diary (eDiary). If participants get a daily insulin they will record their insulin doses in the eDiary. If Participants get weekly insulin icodec, participants study phone will also have the DoseGuide App. The DoseGuide App gives dose recommendations based on their blood sugar and previous doses. Participants will record their insulin doses in the DoseGuide App. The study will last for about 1 year and 2 months. Participants will have 8 planned clinic visits with the study doctor. More visits will be planned to meet individual needs. At 6 clinic visits participants will have blood samples taken. Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.
Interventions
DRUGInsulin icodec
Participants will receive subcutaneous (s.c.) injections of insulin icodec once weekly for 52 weeks.
DRUGInsulin Glargine 100U/mL
Participants will receive subcutaneous (s.c.) injections of insulin analogues once daily for 52 weeks.
DRUGInsulin Degludec
Participants will receive subcutaneous (s.c.) injections of insulin analogues once daily for 52 weeks.
DRUGInsulin Glargine 300U/mL
Participants will receive subcutaneous (s.c.) injections of insulin analogues once daily for 52 weeks.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. * Male or female. * Age above or equal to 18 years at the time of signing informed consent. * Diagnosed with T2D greater than or equal to 180 days prior to the day of screening. * HbA1c above 7.0% (53 mmol/mol) as measured by central lab. * Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes. * Stable daily dose(s) greater than or equal to 90 days prior to the day of screening of any of the following antidiabetic drug(s) or combination regimen(s): a .Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. b .Any metformin combination formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. c. Any of the following non-insulin antidiabetic drug classes including combinations (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose):i). Sulfonylureas ii). Meglitinides (glinides) iii). DPP-4 inhibitors iv. SGLT2 inhibitors v). Thiazolidinediones vi). Alpha-glucosidase inhibitors vii). Oral combination products (for the allowed individual Oral Antidiabetic Drugs (OADs)) viii). Oral or injectable GLP-1-receptor agonists. * Intensification with insulin is indicated to achieve glycaemic target (4.4-7.2 mmol/L, 80-130 mg/dL) at the discretion of the treating investigator.
Exclusion criteria
* Known or suspected hypersensitivity to trial product(s) or related products. * Previous participation in this trial. Participation is defined as signed informed consent. * Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice). * Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening. (Simultaneous participation in a trial with the primary objective of evaluating an approved or non-approved investigational medicinal product for prevention or treatment of COVID-19 disease or postinfectious conditions is allowed if the last dose of the investigational medicinal product has been received more than 30 days before screening) * Any disorder which in the investigator's opinion might jeopardise subject's safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycated Haemoglobin (HbA1c) | Baseline (week 0), week 52 | Change in HbA1c from baseline (week 0) to week 52 is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Baseline to Treatment Discontinuation or Intensification | From baseline (week 0) to week 52 | Time from baseline to treatment discontinuation or intensification from baseline (week 0) to week 52 is presented. |
| Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction | Baseline (week 0), week 52 | Change in DTSQs in total treatment satisfaction is presented. The DTSQs questionnaire was used to assess participants treatment satisfaction which contained 8 components (DTSQs Item 1-8 : how satisfied are you with your current treatment, how often have you felt that blood sugars have been unacceptably high, how often have you felt that blood sugars have been unacceptably low, how convenient have you been finding your treatment to be recently, how flexible have you been finding your treatment to be recently, how satisfied are you with your understanding of your diabetes, would you recommend treatment to someone else with your kind of diabetes, how satisfied would you be to continue with present form of treatment). The result presented is the treatment satisfaction summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Total scores for treatment satisfaction range from 0-36 with 0 being the lowest and 36 being the highest score in total treatment satisfaction. |
| Treatment Related Impact Measure for Diabetes (TRIM-D) Compliance Domain | At end of treatment (week 52) | Treatment Related Impact Measure for Diabetes (TRIM-D) Compliance domain at week 52 is presented. The TRIM-D questionnaire was developed to capture the impact of diabetes treatment on patients' functioning and well-being. The questionnaire was used to measure the compliance between the treatment groups. The total TRIM-D compliance score is computed by summing across the items and then transforming to a 0-100 scale with higher score indicating better compliance. |
| Number of Severe Hypoglycaemic Episodes (Level 3) | From baseline (week 0) to week 57 | Number of severe hypoglycaemic episodes (level 3) is presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. |
| Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 Millimoles Per Liter [mmol/L] (54 Milligrams Per Deciliter [mg/dL]), Confirmed by Blood Glucose (BG) Meter) | From baseline (week 0) to week 57 | Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 millimoles per liter \[mmol/L\] (54 mg/dL), confirmed by BG meter) is presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. |
| Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3) | From baseline (week 0) to week 57 | Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) is presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. |
Countries
Bulgaria, Canada, Germany, Greece, Hungary, Poland, Puerto Rico, Serbia, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORClinical Transparency (dept. 1452)
Novo Nordisk A/S
Participant flow
Recruitment details
The trial was conducted at 182 sites in Canada, Germany, Greece, Hungary, Poland, Turkey and the United States.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Icodec Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec guided by the DoseGuide app, for 52 weeks using PDS290 prefilled pen-injector. Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. | 542 |
| Once Daily Basal Insulin Analogue Participants were to receive once daily basal insulin analogue of (Insulin degludec using PDS290 prefilled pen-injector) or (Insulin glargine U100 or Insulin glargine U300 using SoloSTAR® pre-filled pen-injector) for 52 weeks, at a dose in accordance with local label. Titration of once daily basal insulin analogue comparators is at the discretion of the investigator according to local clinical practice. The recommended doses for all once daily basal insulin analogues was based on the locally approved label. | 543 |
| Total | 1,085 |
Baseline characteristics
| Characteristic | Once Daily Basal Insulin Analogue | Total | Insulin Icodec |
|---|---|---|---|
| Age, Continuous | 59.39 Years STANDARD_DEVIATION 10.15 | 59.27 Years STANDARD_DEVIATION 10.47 | 59.15 Years STANDARD_DEVIATION 10.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants | 95 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 499 Participants | 989 Participants | 490 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 19 Participants | 47 Participants | 28 Participants |
| Race/Ethnicity, Customized Black Or African American | 28 Participants | 52 Participants | 24 Participants |
| Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 8 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 493 Participants | 971 Participants | 478 Participants |
| Sex: Female, Male Female | 230 Participants | 463 Participants | 233 Participants |
| Sex: Female, Male Male | 313 Participants | 622 Participants | 309 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 542 | 6 / 543 |
| other Total, other adverse events | 43 / 542 | 55 / 538 |
| serious Total, serious adverse events | 45 / 542 | 57 / 538 |
Outcome results
Primary
Change in Glycated Haemoglobin (HbA1c)
Change in HbA1c from baseline (week 0) to week 52 is presented.
Time frame: Baseline (week 0), week 52
Population: Full analysis set included all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Icodec | Change in Glycated Haemoglobin (HbA1c) | -1.68 Percentage of HbA1c | Standard Error 0.09 |
| Once Daily Basal Insulin Analogue | Change in Glycated Haemoglobin (HbA1c) | -1.31 Percentage of HbA1c | Standard Error 0.12 |
Comparison: The response and change from baseline in response after 52 weeks were analysed using an analysis of covariance (ANCOVA) model with region and randomised treatment as fixed factors, and baseline HbA1c as a covariate.p-value: <0.000195% CI: [-0.66, -0.09]ANCOVA
Secondary
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction
Change in DTSQs in total treatment satisfaction is presented. The DTSQs questionnaire was used to assess participants treatment satisfaction which contained 8 components (DTSQs Item 1-8 : how satisfied are you with your current treatment, how often have you felt that blood sugars have been unacceptably high, how often have you felt that blood sugars have been unacceptably low, how convenient have you been finding your treatment to be recently, how flexible have you been finding your treatment to be recently, how satisfied are you with your understanding of your diabetes, would you recommend treatment to someone else with your kind of diabetes, how satisfied would you be to continue with present form of treatment). The result presented is the treatment satisfaction summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Total scores for treatment satisfaction range from 0-36 with 0 being the lowest and 36 being the highest score in total treatment satisfaction.
Time frame: Baseline (week 0), week 52
Population: Full analysis set included all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Icodec | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction | 4.68 Score on a scale | Standard Error 0.25 |
| Once Daily Basal Insulin Analogue | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction | 3.90 Score on a scale | Standard Error 0.25 |
Secondary
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 Millimoles Per Liter [mmol/L] (54 Milligrams Per Deciliter [mg/dL]), Confirmed by Blood Glucose (BG) Meter)
Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 millimoles per liter \[mmol/L\] (54 mg/dL), confirmed by BG meter) is presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter.
Time frame: From baseline (week 0) to week 57
Population: Safety analysis set included all participants who were randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Icodec | Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 Millimoles Per Liter [mmol/L] (54 Milligrams Per Deciliter [mg/dL]), Confirmed by Blood Glucose (BG) Meter) | 104 Episodes |
| Once Daily Basal Insulin Analogue | Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 Millimoles Per Liter [mmol/L] (54 Milligrams Per Deciliter [mg/dL]), Confirmed by Blood Glucose (BG) Meter) | 76 Episodes |
Secondary
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)
Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) is presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery.
Time frame: From baseline (week 0) to week 57
Population: Safety analysis set included all participants who were randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Icodec | Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3) | 104 Episodes |
| Once Daily Basal Insulin Analogue | Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3) | 81 Episodes |
Secondary
Number of Severe Hypoglycaemic Episodes (Level 3)
Number of severe hypoglycaemic episodes (level 3) is presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery.
Time frame: From baseline (week 0) to week 57
Population: Safety analysis set included all participants who were randomly assigned to trial treatment and who took at least 1 dose of trial product. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Icodec | Number of Severe Hypoglycaemic Episodes (Level 3) | 0 Episodes |
| Once Daily Basal Insulin Analogue | Number of Severe Hypoglycaemic Episodes (Level 3) | 5 Episodes |
Secondary
Time From Baseline to Treatment Discontinuation or Intensification
Time from baseline to treatment discontinuation or intensification from baseline (week 0) to week 52 is presented.
Time frame: From baseline (week 0) to week 52
Population: FAS included all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin Icodec | Time From Baseline to Treatment Discontinuation or Intensification | 20.1 Weeks |
| Once Daily Basal Insulin Analogue | Time From Baseline to Treatment Discontinuation or Intensification | 13.9 Weeks |
Secondary
Treatment Related Impact Measure for Diabetes (TRIM-D) Compliance Domain
Treatment Related Impact Measure for Diabetes (TRIM-D) Compliance domain at week 52 is presented. The TRIM-D questionnaire was developed to capture the impact of diabetes treatment on patients' functioning and well-being. The questionnaire was used to measure the compliance between the treatment groups. The total TRIM-D compliance score is computed by summing across the items and then transforming to a 0-100 scale with higher score indicating better compliance.
Time frame: At end of treatment (week 52)
Population: FAS included all randomised subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Icodec | Treatment Related Impact Measure for Diabetes (TRIM-D) Compliance Domain | 90.42 Score on a scale | Standard Error 0.64 |
| Once Daily Basal Insulin Analogue | Treatment Related Impact Measure for Diabetes (TRIM-D) Compliance Domain | 87.37 Score on a scale | Standard Error 0.64 |