Diabetes Mellitus, Type 2
Conditions
Brief summary
This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to semaglutide taken once a week in people with type 2 diabetes. The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to semaglutide. Participants will either get IcoSema or semaglutide. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe semaglutide in many countries. Participants will get IcoSema or semaglutide, which they must inject once a week with a pen, which has a small needle, in a skin fold in the thigh, upper arm, or stomach. The study will last for about 1 year and 1 month. Participants will have 18 clinic visits, 34 phone/video calls with the study doctor, and 4 contacts with the site that can either be clinic visits or phone/video calls. At 11 clinic visits participants will have blood samples taken. At 7 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit. Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.
Interventions
DRUGIcoSema
IcoSema once weekly subcutaneously (s.c., under the skin) using a needle and a pen. For about 1 year and 1 month.
DRUGSemaglutide 1 mg
Semaglutide once weekly subcutaneously (s.c., under the skin). Dose titrated to 1mg over 8 weeks (0.25 mg for 4 weeks, 0.5 mg for 4 weeks). For about 1 year and 1 month.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female and age above or equal to 18 years at the time of signing informed consent. * Diagnosed with type 2 diabetes mellitus 180 days or more before screening. * HbA1c of 7.0 - 10.0% (53.0 - 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening. * Insulin naïve. The following exceptions are permitted: short term insulin treatment for a maximum of 14 days before screening and/or prior insulin treatment for gestational diabetes. * Treated with stable doses of daily or weekly GLP-1 receptor agonist (excluding once weekly semaglutide with doses higher than 1.0 mg) according to local label for the treatment of diabetes for 90 days or more before screening. The treatment can be with or without any of the following anti diabetic drugs with stable doses for 90 days or more before screening: Metformin - Sulfonylureas (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Meglitinides (glinides)(Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - DPP 4 inhibitors (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Sodium glucose co transporter 2 inhibitors - Alpha-glucosidase inhibitors - Thiazolidinediones - Marketed oral combination products only including the products listed above. * Body mass index (BMI) below or equal to 40.0 kg/m\^2.
Exclusion criteria
* Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method. * Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or systemic corticosteroids). * Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. * Any episodes (as declared by the participant or in the medical records) of diabetic ketoacidosis within 90 days before screening. * Presence or history of pancreatitis (acute or chronic) within 180 days before screening. * Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening. * Chronic heart failure classified as being in New York Heart Association Class IV at screening. * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Haemoglobin (HbA1c) | Baseline (week 0), (week 52) | Change from baseline (week 0) to week 52 in HbA1c is presented.The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct participant-site contact; 2) participants who withdrew their informed consent; 3) last participant-investigator contact as defined by the investigator for participants who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of participants who died before any of the above. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline (week 0), (week 52) | Change from baseline (week 0) to week 52 in FPG is presented.The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct participant-site contact; 2) participants who withdrew their informed consent; 3) last participant-investigator contact as defined by the investigator for participants who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of participants who died before any of the above. |
| Change From Baseline in Body Weight | Baseline (week 0), (week 52) | Change from baseline (week 0) to week 52 in body weight is presented. The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct participant-site contact; 2) participants who withdrew their informed consent; 3) last participant-investigator contact as defined by the investigator for participants who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of participants who died before any of the above. |
| Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 Milligram Per Decilitre [mg/dL]) , Confirmed by Blood Glucose [BG] Meter) or Severe Hypoglycaemic Episodes (Level 3) | Week 0 to Week 57 | Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 2 was less than (\<) 3.0 mmol/L (54 mg/dL) and level 3 had no specific glucose threshold. The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets. |
| Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) | Week 0 to Week 57 | Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 2 was \< 3.0 mmol/L (54 mg/dL). The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets. |
| Number of Severe Hypoglycaemic Episodes (Level 3) | Week 0 to Week 57 | Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 3 had no specific glucose threshold.The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets. |
Countries
Brazil, Canada, China, France, Greece, Hungary, Israel, Japan, Russia, Slovakia, Sweden, Switzerland, Taiwan, Ukraine, United States
Contacts
STUDY_DIRECTORClinical Transparency (dept. 1452)
Novo Nordisk A/S
Participant flow
Recruitment details
The trial was conducted at 124 sites in 13 countries.
Pre-assignment details
Participants were randomised in 1:1 ratio to receive subcutaneous (s.c.) injection of either IcoSema or semaglutide once weekly. The trial had a 52-week treatment period followed by a 5-week follow-up period.
Participants by arm
| Arm | Count |
|---|---|
| IcoSema Participants received once weekly 700 units per millilitre (U/mL) of insulin icodec and 2 milligram per millilitre (mg/mL) of semaglutide subcutaneously for 52 weeks. 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: \< 4.4 mmol/L: dose re-duced by 10 U; 4.4-7.2 mmol/L: no adjustment; \> 7.2 mmol/L: dose increased by 10 U. Dose titration of IcoSema was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured weekly. | 342 |
| Semaglutide Participants received once weekly semaglutide subcutaneously in a dose escalation manner, with dose increases every 4 weeks for up to week 8 (0.25 milligrams \[mg\], 0.5 mg) followed by dose of 1.0 mg once weekly up to the end of treatment period. | 341 |
| Total | 683 |
Baseline characteristics
| Characteristic | IcoSema | Semaglutide | Total |
|---|---|---|---|
| Age, Continuous | 59.9 Years STANDARD_DEVIATION 10.5 | 58.3 Years STANDARD_DEVIATION 9.8 | 59.1 Years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 37 Participants | 37 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 285 Participants | 289 Participants | 574 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 20 Participants | 15 Participants | 35 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 99 Participants | 90 Participants | 189 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 9 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 20 Participants | 15 Participants | 35 Participants |
| Race (NIH/OMB) White | 210 Participants | 224 Participants | 434 Participants |
| Sex: Female, Male Female | 141 Participants | 145 Participants | 286 Participants |
| Sex: Female, Male Male | 201 Participants | 196 Participants | 397 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 342 | 0 / 341 |
| other Total, other adverse events | 163 / 341 | 159 / 340 |
| serious Total, serious adverse events | 38 / 341 | 21 / 340 |
Outcome results
Primary
Change From Baseline in Glycosylated Haemoglobin (HbA1c)
Change from baseline (week 0) to week 52 in HbA1c is presented.The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct participant-site contact; 2) participants who withdrew their informed consent; 3) last participant-investigator contact as defined by the investigator for participants who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of participants who died before any of the above.
Time frame: Baseline (week 0), (week 52)
Population: Full Analysis Set (FAS) which comprised all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IcoSema | Change From Baseline in Glycosylated Haemoglobin (HbA1c) | -1.40 Percentage point of HbA1c | Standard Deviation 0.91 |
| Semaglutide | Change From Baseline in Glycosylated Haemoglobin (HbA1c) | -0.86 Percentage point of HbA1c | Standard Deviation 0.96 |
Comparison: Treatment policy strategyp-value: <0.000195% CI: [-0.56, -0.33]ANCOVA
Secondary
Change From Baseline in Body Weight
Change from baseline (week 0) to week 52 in body weight is presented. The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct participant-site contact; 2) participants who withdrew their informed consent; 3) last participant-investigator contact as defined by the investigator for participants who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of participants who died before any of the above.
Time frame: Baseline (week 0), (week 52)
Population: FAS which comprised all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IcoSema | Change From Baseline in Body Weight | 0.89 Kilogram (kg) | Standard Deviation 4.36 |
| Semaglutide | Change From Baseline in Body Weight | -3.77 Kilogram (kg) | Standard Deviation 4.6 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG)
Change from baseline (week 0) to week 52 in FPG is presented.The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct participant-site contact; 2) participants who withdrew their informed consent; 3) last participant-investigator contact as defined by the investigator for participants who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of participants who died before any of the above.
Time frame: Baseline (week 0), (week 52)
Population: FAS which comprised all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IcoSema | Change From Baseline in Fasting Plasma Glucose (FPG) | -2.74 Millimoles per litre (mmol/L) | Standard Deviation 2.85 |
| Semaglutide | Change From Baseline in Fasting Plasma Glucose (FPG) | -1.41 Millimoles per litre (mmol/L) | Standard Deviation 2.89 |
Secondary
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter)
Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 2 was \< 3.0 mmol/L (54 mg/dL). The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets.
Time frame: Week 0 to Week 57
Population: SAS included all participants exposed to randomised treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IcoSema | Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) | 15 Episodes |
| Semaglutide | Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) | 13 Episodes |
Secondary
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 Milligram Per Decilitre [mg/dL]) , Confirmed by Blood Glucose [BG] Meter) or Severe Hypoglycaemic Episodes (Level 3)
Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 2 was less than (\<) 3.0 mmol/L (54 mg/dL) and level 3 had no specific glucose threshold. The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets.
Time frame: Week 0 to Week 57
Population: Safety Analysis Set (SAS) included all participants exposed to randomised treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IcoSema | Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 Milligram Per Decilitre [mg/dL]) , Confirmed by Blood Glucose [BG] Meter) or Severe Hypoglycaemic Episodes (Level 3) | 15 Episodes |
| Semaglutide | Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 Milligram Per Decilitre [mg/dL]) , Confirmed by Blood Glucose [BG] Meter) or Severe Hypoglycaemic Episodes (Level 3) | 13 Episodes |
Secondary
Number of Severe Hypoglycaemic Episodes (Level 3)
Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 3 had no specific glucose threshold.The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets.
Time frame: Week 0 to Week 57
Population: SAS included all participants exposed to randomised treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IcoSema | Number of Severe Hypoglycaemic Episodes (Level 3) | 0 Episodes |
| Semaglutide | Number of Severe Hypoglycaemic Episodes (Level 3) | 0 Episodes |