A Phase 3 interventional study of Insulin degludec/liraglutide and Insulin degludec in Diabetes and Diabetes Mellitus, Type 2, sponsored by Novo Nordisk A/S. Completed at 36 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-12-14.
Sponsored by Novo Nordisk A/S · Phase 3, Interventional, and Treatment
This trial is conducted in Asia. The aim of this trial is to confirm the efficacy of insulin degludec/liraglutide in controlling glycaemia in Chinese subjects with type 2 diabetes mellitus inadequately controlled on oral antidiabetic agents
10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.
This study's enrollment of 720 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.
Browse Diabetes Mellitus studies →Novo Nordisk A/S is the lead sponsor of 1,370 studies on the registry; 102 are open to participants now.
Of its 198 completed or terminated interventional studies of FDA-regulated products, 94 (47%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Drug: Insulin degludec/liraglutide
Drug: Insulin degludec
Drug: Liraglutide
Subcutaneously (s.c., under the skin)administration once daily in combination with metformin. For 26 weeks.
Subcutaneously (s.c., under the skin)administration once daily in combination with metformin. For 26 weeks.
Subcutaneously (s.c., under the skin)administration once daily in combination with metformin. For 26 weeks.
Change in HbA1c
Change in HbA1c from baseline (week 0) after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Body Weight
Change in body weight from baseline (week 0) after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Number of Treatment Emergent Severe or BG Confirmed Hypoglycaemic Episodes
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or blood glucose (BG) confirmed by a plasma glucose (PG) value \< 3.1 millimoles per liter (mmol/L) with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. The number of episodes are represented as rates. The observed rates of treatment-emergent severe or BG confirmed hypoglycaemic episodes per patient years of exposure (PYE) (number of episodes divided by PYE multiplied by 100) during 26 weeks of treatment are presented.
Time frame: Weeks 0-26
Insulin Dose
The actual daily total insulin dose after 26 weeks of treatment is presented. This outcome measure is only applicable for Insulin degludec/liraglutide and Insulin degludec treatment arms.
Time frame: Week 26
Participants Who Achieved HbA1c < 7.0%, American Diabetes Association (ADA) Target (Yes/no)
Number of participants who achieved ADA HbA1c target (HbA1c \< 7.0%) (yes/no) after 26 weeks of treatment are presented.
Time frame: Week 26
Participants Who Achieved HbA1c ≤ 6.5%, International Diabetes Federation (IDF) Target (Yes/no)
Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment are presented.
Time frame: Week 26
Participants Who Achieved HbA1c <7.0% and Change in Body Weight From Baseline Below or Equal to Zero
Number of participants who achieved ADA HbA1c target (HbA1c \< 7.0%) (yes/no) and change from baseline in body weight below or equal to zero after 26 weeks are presented. Missing values are imputed by LOCF.
Time frame: Week 26
Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero
Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) and change from baseline in body weight below or equal to zero after 26 weeks are presented. Missing values are imputed by LOCF.
Time frame: Week 26
Participants Who Achieved HbA1c < 7.0% Without Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \<3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of participants who achieved ADA HbA1c target (HbA1c \<7.0%) (yes/no) after 26 weeks of treatment and without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment are presented. Missing values are imputed by LOCF.
Time frame: Week 26
Participants Who Achieved HbA1c ≤ 6.5% Without Severe or BG Confirmed Hypoglycaemic Episodes
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \< 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment and without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment are presented. Missing values are imputed by LOCF.
Time frame: Week 26
Participants Who Achieved HbA1c < 7.0% Without Severe or BG Confirmed Episodes, and Change From Baseline in Body Weight Below or Equal to Zero.
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \< 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of participants who achieved ADA HbA1c target (HbA1c \< 7.0%) (yes/no) after 26 weeks of treatment without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment and with change from baseline in body weight below or equal to zero are presented. Missing values are imputed by LOCF.
Time frame: Week 26
Participants Who Achieved HbA1c ≤ 6.5% Without Severe or BG Confirmed Episodes and Change From Baseline in Body Weight Below or Equal to Zero.
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \< 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment and with change from baseline in body weight below or equal to zero are presented. Missing values are imputed by LOCF.
Time frame: Week 26
Change in Fasting Plasma Glucose (FPG)
Change from baseline (week 0) in FPG after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Waist Circumferance
Change from baseline (week 0) in waist circumferance after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
9-point SMPG Profile
Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values at 26 weeks of treatment are presented.
Time frame: Week 26
Change in Mean of 9-point SMPG Profile
Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). The mean of profile is defined as the area under the profile divided by measurement time and is calculated using the trapezoidal method. Change in mean of the 9-point SMPG profile from baseline (week 0) to week 26 is presented.
Time frame: Week 0, week 26
Change in Mean Post-prandial Plasma Glucose (PG) Increments
Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Post-prandial SMPG increments from before meal to 90 minutes after for breakfast, lunch and dinner were calculated. The mean increment over all meals was derived as the mean of all available meal increments. Change from baseline (week 0) in post-prandial SMPG increments for all meals after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Fasting C-peptide - Ratio to Baseline
Change in fasting C-peptide (measured in nanomoles per liter \[nmol/L\]) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time frame: Week 0, week 26
Change in Fasting Human Insulin - Ratio to Baseline
Change in fasting human insulin (measured in picomoles per liter \[pmol/L\]) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time frame: Week 0, week 26
Change in Fasting Glucagon - Ratio to Baseline
Change in fasting glucagon (measured in picograms per milliliter \[pg/mL\]) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time frame: Week 0, week 26
Change in HOMA-B (Beta Cell Function)- Ratio to Baseline
Change in HOMA-B (measured in %) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time frame: Week 0, week 26
Change in Fasting Total Cholesterol - Ratio to Baseline
Change in fasting total cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time frame: Week 0, week 26
Change in Fasting High Density Lipoprotein (HDL) Cholesterol- Ratio to Baseline
Change in fasting HDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline
Time frame: Week 0, week 26
Change in Fasting Low Density Lipoprotein (LDL) Cholesterol- Ratio to Baseline
Change in fasting LDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time frame: Week 0, week 26
Change in Fasting Very Low-density Lipoprotein (VLDL) Cholesterol- Ratio to Baseline
Change in fasting VLDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline
Time frame: Week 0, week 26
Change in Fasting Triglycerides - Ratio to Baseline.
Change in fasting triglycerides (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time frame: Week 0, week 26
Change in Fasting Free Fatty Acid - Ratio to Baseline
Change in fasting free fatty acid (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time frame: Week 0, week 26
Number of Treatment-emergent Adverse Events (TEAE)
A TEAE was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. The observed rates of adverse events (AEs) per patient years of exposure (PYE) (number of AEs divided by PYE multiplied by 100) after 26 weeks are presented.
Time frame: Weeks 0-26
Number of Treatment Emergent Nocturnal Severe or BG Confirmed Hypoglycaemic Episodes.
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \< 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Hypoglycaemic episodes were defined as nocturnal if the time of the onset was between 00:01 and 05.59 both inclusive. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
Time frame: Weeks 0-26
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes.
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
Time frame: Weeks 0-26
Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Hypoglycaemic episodes were defined as nocturnal if the time of the onset was between 00:01 and 05.59 both inclusive. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
Time frame: Weeks 0-26
Number of Treatment Emergent Hypoglycaemic Episodes According to ADA Definition
A hypoglycaemic episode was defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. The number of episodes are represented as rates. The observed rates of episodes (according to the ADA definition) per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
Time frame: Weeks 0-26
Change in Physical Examination
Physical examination parameters are categorised as cardiovascular system; central and peripheral nervous system; gastrointestinal system including mouth; general appearance; head, ears, eyes, nose, throat, neck; lymph node palpation; musculoskeletal system; respiratory system; skin and thyroid gland. The number of participants assessed as normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) at screening (week -2) and week 26 per each category is presented.
Time frame: Week -2, week 26
Eye Examination
Dilated fundoscopy or fundus photography was performed by the investigator at screening (week -2) and week 26. The results of the examination were interpreted for each eye (left and right) and are categorised as normal, abnormal NCS or abnormal CS. Number of participants in each category at screening (week -2) and week 26 is presented.
Time frame: Week -2, Week 26
Change in Electrocardiogram (ECG)
Electrocardiogram was assessed by the investigator as normal, abnormal NCS and abnormal CS. Number of participants at screening (week -2) and at week 26 is presented.
Time frame: Week -2, week 26
Change in Pulse
Change in pulse from baseline (week 0) after 26 weeks of treatment is presented
Time frame: Week 0, week 26
Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
Change in blood pressure (systolic and diastolic blood pressure) from baseline (week 0) after 26 weeks of treatment is presented
Time frame: Week 0, week 26
Change in Biochemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Amalyse, Lipase, Creatiine Kinase Serum
Change in alkaline phosphatase, ALT, AST, creatine kinase, amylase, lipase, creatine kinase serum from baseline (week 0) after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Biochemistry Parameters (Albumin Serum, Total Protein)
Change in total protein, albumin serum from baseline (week 0) after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Biochemistry Parameters: Calcium Serum (Total), Calcium Corrected Serum, Potassium Serum, Sodium Serum, Urea Serum
Change in calcium serum (total), calcium corrected serum, potassium serum, sodium serum, urea serum from baseline (week 0) after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Biochemistry Parameters: Total Bilirubin Serum, Creatinine Serum
Change in total bilirubin serum, creatinine serum from baseline (week 0) after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Haematological Parameter: Erythrocytes Blood
Change in erythrocyte blood from baseline (week 0) after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Haematological Parameter: Haematocrits
Change in haematocrits from baseline (week 0) after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Haemotological Parameter- Eosinophils
Change in eosinophils from baseline after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Haematological Parameter - Neutrophils
Change in neutrophils from baseline (week 0) after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Haematological Parameter: Basophils
Change in basophils from baseline (week 0) after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Haemotological Parameter- Monocytes
Change in monocytes from baseline (week 0) after 26 weeks of treatment is presented
Time frame: Week 0, week 26
Change in Haematological Parameter - Lymphocytes
Change in lymphocytes from baseline (week 0) after 26 weeks of treatment is presented
Time frame: Week 0, week 26
Change in Haematology: Haemoglobin Blood
Change in haemoglobin from baseline (week 0) after 26 weeks of treatment is presented.
Time frame: Week 0, week 26
Change in Haematologcal Parameter: Leukocytes
Change in leukocytes from baseline (week 0) after 26 weeks of treatment
Time frame: Week 0, week 26
Change in Haematological Parameter: Thrombocytes
Change in thrombocytes from baseline (week 0) after 26 weeks of treatment
Time frame: Week 0, week 26
Change in Calcitonin
Calcitonin levels were measured and were categorised as low, normal or high in relation to reference range (8.31- 14.3 picogram/milliliter \[pg/mL\]). Number of participants in each category at baseline (week 0) and week 26 are presented.
Time frame: Week 0, week 26
Urinalysis (Protein, Glucose, Erythrocytes and Ketones)
The urinalysis assessment was the measurements of protein, glucose, erythrocytes and ketones in urine at baseline (week 0) and week 26 and categorised as negative, trace and positive. Number of participants in each category at week 0 and week 26 is presented.
Time frame: Week 0, week 26
Occurence of Anti-insulin Degludec Specific Antibodies
This outcome measure is only applicable for the insulin degludec/liraglutide arm and insulin degludec arm. Serum samples were analysed for the presence of anti-insulin degludec specific antibodies. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (T).
Time frame: Week 27
Occurence of Antibodies Cross-reacting to Human Insulin
This outcome measure is only applicable for the insulin degludec/liraglutide arm and insulin degludec arm. Serum samples were analysed for the presence of cross-reacting antibodies to human insulin. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (T).
Time frame: Week 27
Occurence of Total Insulin Antibodies
This outcome measure is only applicable for the Insulin degludec/liraglutide arm and Insulin degludec arm. Serum samples were analysed for the presence of antobodies to human insulin. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (T).
Time frame: Week 27
Occurence of Anti-liraglutide Antibodies
This outcome measure is applicable for the Insulin degludec/liraglutide arm and the liraglutide arm. Serum samples were analysed for the presence of anti-liraglutide antibodies. Number of participants who were assessed for anti-liraglutide antibodies at week 27 are presented.
Time frame: Week 27
Occurence of Antibodies Cross-reacting to Native Glucagon-like Peptide (GLP-1)
This outcome measure is applicable to the Insulin degludec/liraglutide arm and the liraglutide arm. Serum samples were analysed for the presence of cross-reacting antibodies to native GLP-1. Number of participants who measured with anti-liraglutide antibodies cross reacting native GLP-1 at week 27 are presented.
Time frame: Week 27
Occurence of Neutralising Liraglutide Antibodies
This outcome measure is only applicable for the Insulin degludec/liraglutide arm and liraglutide arm. Neutralising antibodies were assessed when the corresponding anti-Liraglutide antibody were positive at week 27. Number of participants who measured with neutralising liraglutide antibodies at week 27 are presented.
Time frame: Week 27
Occurence of Neutralising Antibodies Cross-reacting to Native GLP-1
This outcome measure is only applicable for the Insulin degludec/liraglutide arm and liraglutide arm. Cross reacting antibodies were assessed when anti-liraglutide antibody was positive. Number of participants who measured with neutralising liraglutide antibodies cross-reacting to native GLP-1 at week 27 are presented.
Time frame: Week 27
Serum Concentrations of Insulin Degludec
This outcome measure is applicable for Insulin degludec and Insulin degludec/liraglutide arms. Serum samples from the Insulin degludec/liraglutide and Insulin degludec arms were assayed using population PK analysis. The maximum serum concentrations (Cmax) are summarised for the two arms.
Time frame: Week 0, week 26
Plasma Concentration of Liraglutide
This outcome measure is for Insulin degludec/liraglutide and liraglutide arms. Serum samples from the Insulin degludec/liraglutide and liraglutide arms were assayed using population PK analysis. The Cmax are summarised for the two arms.
Time frame: Week 0, week 26
The trial was conducted at 38 sites in China mainland.
| Milestone | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Started | 361 | 179 | 180 |
| Full analysis set (fas) | 361 | 179 | 180 |
| Safety analysis set (sas) | 358 | 175 | 180 |
| Exposed | 358 | 175 | 180 |
| Completed | 341 | 167 | 151 |
| Not completed | 20 | 12 | 29 |
| Withdrew: Adverse event | 5 | 1 | 15 |
| Withdrew: Protocol violation | 3 | 2 | 1 |
| Withdrew: Lack of efficacy | 0 | 0 | 4 |
| Withdrew: Pregnancy | 0 | 1 | 0 |
| Withdrew: Withdrawal by subject | 10 | 8 | 8 |
| Withdrew: Severe hypoglycaemic episode | 0 | 0 | 1 |
| Withdrew: Non-compliance towards treatment | 2 | 0 | 0 |
Change in HbA1c from baseline (week 0) after 26 weeks of treatment is presented.
| Percentage points of HbA1c | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in HbA1c | -1.71 ± 0.88 | -1.20 ± 0.99 | -1.16 ± 0.89 |
Change in body weight from baseline (week 0) after 26 weeks of treatment is presented.
| Kilogram (Kg) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Body Weight | 0.2 ± 2.7 | 1.3 ± 2.7 | -2.5 ± 2.7 |
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or blood glucose (BG) confirmed by a plasma glucose (PG) value \< 3.1 millimoles per liter (mmol/L) with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. The number of episodes are represented as rates. The observed rates of treatment-emergent severe or BG confirmed hypoglycaemic episodes per patient years of exposure (PYE) (number of episodes divided by PYE multiplied by 100) during 26 weeks of treatment are presented.
| (Number of episodes/PYE)*100 | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Number of Treatment Emergent Severe or BG Confirmed Hypoglycaemic Episodes | 23.94 | 17.01 | 3.60 |
The actual daily total insulin dose after 26 weeks of treatment is presented. This outcome measure is only applicable for Insulin degludec/liraglutide and Insulin degludec treatment arms.
| Units of insulin (U) | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Insulin Dose | 24.8 ± 11.9 | 30.1 ± 14.4 |
Number of participants who achieved ADA HbA1c target (HbA1c \< 7.0%) (yes/no) after 26 weeks of treatment are presented.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Yes | 272 | 83 | 80 |
| No | 69 | 84 | 71 |
Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment are presented.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Yes | 201 | 48 | 41 |
| No | 140 | 119 | 110 |
Number of participants who achieved ADA HbA1c target (HbA1c \< 7.0%) (yes/no) and change from baseline in body weight below or equal to zero after 26 weeks are presented. Missing values are imputed by LOCF.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Yes | 147 | 34 | 74 |
| No | 214 | 145 | 106 |
Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) and change from baseline in body weight below or equal to zero after 26 weeks are presented. Missing values are imputed by LOCF.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Yes | 111 | 21 | 37 |
| No | 250 | 158 | 143 |
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \<3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of participants who achieved ADA HbA1c target (HbA1c \<7.0%) (yes/no) after 26 weeks of treatment and without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment are presented. Missing values are imputed by LOCF.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Yes | 265 | 80 | 84 |
| No | 96 | 99 | 96 |
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \< 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment and without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment are presented. Missing values are imputed by LOCF.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Yes | 195 | 46 | 43 |
| No | 166 | 133 | 137 |
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \< 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of participants who achieved ADA HbA1c target (HbA1c \< 7.0%) (yes/no) after 26 weeks of treatment without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment and with change from baseline in body weight below or equal to zero are presented. Missing values are imputed by LOCF.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Yes | 136 | 33 | 72 |
| No | 225 | 146 | 108 |
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \< 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment and with change from baseline in body weight below or equal to zero are presented. Missing values are imputed by LOCF.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Yes | 103 | 21 | 36 |
| No | 258 | 158 | 144 |
Change from baseline (week 0) in FPG after 26 weeks of treatment is presented.
| mmol/L | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Fasting Plasma Glucose (FPG) | -3.64 ± 2.27 | -3.45 ± 2.34 | -1.86 ± 2.11 |
Change from baseline (week 0) in waist circumferance after 26 weeks of treatment is presented.
| Centimeters (cm) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Waist Circumferance | -0.3 ± 3.4 | 1.2 ± 4.2 | -2.6 ± 3.8 |
Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values at 26 weeks of treatment are presented.
| mmol/L | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Before breakfast | 5.41 ± 1.07 | 5.66 ± 1.20 | 6.89 ± 1.37 |
| 90 minutes after the start of breakfast | 8.97 ± 2.48 | 9.85 ± 2.73 | 10.04 ± 2.81 |
| Before lunch | 6.31 ± 1.80 | 7.10 ± 2.35 | 7.48 ± 2.14 |
| 90 minutes after the start of the lunch | 8.87 ± 2.15 | 10.18 ± 2.81 | 9.54 ± 2.43 |
| Before dinner | 6.52 ± 1.77 | 7.39 ± 2.23 | 7.50 ± 2.11 |
| 90 minutes after start of the dinner | 9.33 ± 2.40 | 10.27 ± 2.68 | 9.45 ± 2.13 |
| At bedtime | 7.99 ± 2.28 | 8.86 ± 2.38 | 8.49 ± 2.26 |
| At 4:00 am | 5.60 ± 1.26 | 6.12 ± 1.75 | 6.86 ± 1.60 |
| Before breakfast the following day | 5.35 ± 0.96 | 5.47 ± 1.07 | 6.81 ± 1.47 |
Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). The mean of profile is defined as the area under the profile divided by measurement time and is calculated using the trapezoidal method. Change in mean of the 9-point SMPG profile from baseline (week 0) to week 26 is presented.
| mmol/L | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Mean of 9-point SMPG Profile | -3.17 ± 2.16 | -2.47 ± 2.14 | -2.13 ± 2.02 |
Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Post-prandial SMPG increments from before meal to 90 minutes after for breakfast, lunch and dinner were calculated. The mean increment over all meals was derived as the mean of all available meal increments. Change from baseline (week 0) in post-prandial SMPG increments for all meals after 26 weeks of treatment is presented.
| mmol/L | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Mean Post-prandial Plasma Glucose (PG) Increments | -0.20 ± 2.40 | 0.09 ± 2.40 | -0.54 ± 2.57 |
Change in fasting C-peptide (measured in nanomoles per liter \[nmol/L\]) from baseline (week 0) to week 26 is presented as ratio to baseline.
| Ratio of fasting C-peptide | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Fasting C-peptide - Ratio to Baseline | 0.54 ± 52.8 | 0.38 ± 68.5 | 0.98 ± 37.6 |
Change in fasting human insulin (measured in picomoles per liter \[pmol/L\]) from baseline (week 0) to week 26 is presented as ratio to baseline.
| Ratio of fasting human insulin | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Fasting Human Insulin - Ratio to Baseline | 0.53 ± 71.7 | 0.38 ± 77.6 | 1.04 ± 53.3 |
Change in fasting glucagon (measured in picograms per milliliter \[pg/mL\]) from baseline (week 0) to week 26 is presented as ratio to baseline.
| Ratio of fasting glucagon | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Fasting Glucagon - Ratio to Baseline | 0.90 ± 76.6 | 0.95 ± 56.4 | 0.98 ± 75.9 |
Change in HOMA-B (measured in %) from baseline (week 0) to week 26 is presented as ratio to baseline.
| Ratio of HOMA-B (beta cell function) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in HOMA-B (Beta Cell Function)- Ratio to Baseline | 1.38 ± 77.3 | 0.94 ± 77.4 | 1.53 ± 63.8 |
Change in fasting total cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
| Ratio of fasting total cholesterol | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Fasting Total Cholesterol - Ratio to Baseline | 0.94 ± 19.1 | 0.99 ± 16.8 | 0.97 ± 17.7 |
Change in fasting HDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline
| Ratio of fasting HDL cholesterol | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Fasting High Density Lipoprotein (HDL) Cholesterol- Ratio to Baseline | 1.01 ± 14.7 | 1.02 ± 15.7 | 1.03 ± 14.8 |
Change in fasting LDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
| Ratio of fasting LDL cholesterol | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Fasting Low Density Lipoprotein (LDL) Cholesterol- Ratio to Baseline | 0.92 ± 34.2 | 1.01 ± 36.2 | 0.96 ± 34.4 |
Change in fasting VLDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline
| Ratio of fasting VLDL cholesterol | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Fasting Very Low-density Lipoprotein (VLDL) Cholesterol- Ratio to Baseline | 0.90 ± 49.9 | 0.84 ± 47.2 | 0.92 ± 38.6 |
Change in fasting triglycerides (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
| Ratio of fasting triglycerides | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Fasting Triglycerides - Ratio to Baseline. | 0.88 ± 54.4 | 0.82 ± 50.5 | 0.90 ± 45.2 |
Change in fasting free fatty acid (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
| Ratio of fasting free fatty acid | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Fasting Free Fatty Acid - Ratio to Baseline | 0.55 ± 69.9 | 0.48 ± 76.5 | 0.80 ± 69.3 |
A TEAE was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. The observed rates of adverse events (AEs) per patient years of exposure (PYE) (number of AEs divided by PYE multiplied by 100) after 26 weeks are presented.
| (Number of AEs/PYE)*100 | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Number of Treatment-emergent Adverse Events (TEAE) | 410.82 | 306.19 | 541.00 |
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \< 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Hypoglycaemic episodes were defined as nocturnal if the time of the onset was between 00:01 and 05.59 both inclusive. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
| (Number of episodes/PYE)*100 | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Number of Treatment Emergent Nocturnal Severe or BG Confirmed Hypoglycaemic Episodes. | 4.45 | 4.54 | — |
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
| (Number of episodes/PYE)*100 | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes. | 15.03 | 9.07 | 1.20 |
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Hypoglycaemic episodes were defined as nocturnal if the time of the onset was between 00:01 and 05.59 both inclusive. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
| (Number of episodes/PYE)*100 | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | 2.78 | 3.40 | — |
A hypoglycaemic episode was defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. The number of episodes are represented as rates. The observed rates of episodes (according to the ADA definition) per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
| (Number of episodes/PYE)*100 | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Number of Treatment Emergent Hypoglycaemic Episodes According to ADA Definition | 668.55 | 746.20 | 37.19 |
Physical examination parameters are categorised as cardiovascular system; central and peripheral nervous system; gastrointestinal system including mouth; general appearance; head, ears, eyes, nose, throat, neck; lymph node palpation; musculoskeletal system; respiratory system; skin and thyroid gland. The number of participants assessed as normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) at screening (week -2) and week 26 per each category is presented.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Week -2: Cardiovascular system — Normal | 353 | 173 | 180 |
| Week -2: Cardiovascular system — Abnormal, NCS | 2 | 2 | 0 |
| Week -2: Cardiovascular system — Abnormal CS | 3 | 0 | 0 |
| Week 26: Cardiovascular system — Normal | 336 | 166 | 151 |
| Week 26: Cardiovascular system — Abnormal, NCS | 3 | 1 | 0 |
| Week 26: Cardiovascular system — Abnormal CS | 2 | 0 | 0 |
| Week -2: Central and peripheral nervous system — Normal | 355 | 172 | 179 |
| Week -2: Central and peripheral nervous system — Abnormal, NCS | 1 | 0 | 0 |
| Week -2: Central and peripheral nervous system — Abnormal CS | 2 | 3 | 1 |
| Week 26: Central and peripheral nervous system — Normal | 338 | 164 | 150 |
| Week 26: Central and peripheral nervous system — Abnormal, NCS | 1 | 0 | 0 |
| Week 26: Central and peripheral nervous system — Abnormal CS | 2 | 3 | 1 |
| Week -2: Gastrointestinal system including mouth — Normal | 355 | 174 | 179 |
| Week -2: Gastrointestinal system including mouth — Abnormal, NCS | 3 | 1 | 1 |
| Week -2: Gastrointestinal system including mouth — Abnormal CS | 0 | 0 | 0 |
| Week 26: Gastrointestinal system including mouth — Normal | 339 | 166 | 150 |
| Week 26: Gastrointestinal system including mouth — Abnormal, NCS | 2 | 1 | 1 |
| Week 26: Gastrointestinal system including mouth — Abnormal CS | 0 | 0 | 0 |
| Week -2: General appearance — Normal | 351 | 169 | 177 |
| Week -2: General appearance — Abnormal, NCS | 3 | 2 | 1 |
| Week -2: General appearance — Abnormal CS | 4 | 4 | 2 |
| Week 26: General appearance — Normal | 336 | 161 | 150 |
| Week 26: General appearance — Abnormal, NCS | 2 | 2 | 0 |
| Week 26: General appearance — Abnormal CS | 3 | 4 | 1 |
| Week -2: Head, ears, eyes, nose, throat, neck — Normal | 348 | 170 | 175 |
| Week -2: Head, ears, eyes, nose, throat, neck — Abnormal, NCS | 6 | 4 | 3 |
| Week -2: Head, ears, eyes, nose, throat, neck — Abnormal CS | 4 | 1 | 2 |
| Week 26: Head, ears, eyes, nose, throat, neck — Normal | 332 | 164 | 150 |
| Week 26: Head, ears, eyes, nose, throat, neck — Abnormal, NCS | 6 | 3 | 1 |
| Week 26: Head, ears, eyes, nose, throat, neck — Abnormal CS | 3 | 0 | 0 |
| Week -2: Lymph node palpation — Normal | 357 | 174 | 180 |
| Week -2: Lymph node palpation — Abnormal, NCS | 0 | 0 | 0 |
| Week -2: Lymph node palpation — Abnormal CS | 1 | 1 | 0 |
| Week 26: Lymph node palpation — Normal | 340 | 166 | 151 |
| Week 26: Lymph node palpation — Abnormal, NCS | 0 | 0 | 0 |
| Week 26: Lymph node palpation — Abnormal CS | 1 | 1 | 0 |
| Week -2: Musculoskeletal system — Normal | 353 | 172 | 177 |
| Week -2: Musculoskeletal system — Abnormal, NCS | 2 | 2 | 0 |
| Week -2: Musculoskeletal system — Abnormal CS | 3 | 1 | 3 |
| Week 26: Musculoskeletal system — Normal | 332 | 165 | 149 |
| Week 26: Musculoskeletal system — Abnormal, NCS | 2 | 1 | 0 |
| Week 26: Musculoskeletal system — Abnormal CS | 7 | 1 | 2 |
| Week-2: Respiratory system — Normal | 358 | 175 | 180 |
| Week-2: Respiratory system — Abnormal, NCS | 0 | 0 | 0 |
| Week-2: Respiratory system — Abnormal CS | 0 | 0 | 0 |
| Week 26: Respiratory system — Normal | 341 | 167 | 151 |
| Week 26: Respiratory system — Abnormal, NCS | 0 | 0 | 0 |
| Week 26: Respiratory system — Abnormal CS | 0 | 0 | 0 |
| week -2: Skin — Normal | 312 | 152 | 156 |
| week -2: Skin — Abnormal, NCS | 37 | 20 | 20 |
| week -2: Skin — Abnormal CS | 9 | 3 | 4 |
| Week 26: Skin — Normal | 297 | 146 | 134 |
| Week 26: Skin — Abnormal, NCS | 36 | 19 | 15 |
| Week 26: Skin — Abnormal CS | 8 | 2 | 2 |
| Week -2: Thyroid gland — Normal | 348 | 171 | 179 |
| Week -2: Thyroid gland — Abnormal, NCS | 5 | 1 | 1 |
| Week -2: Thyroid gland — Abnormal CS | 5 | 3 | 0 |
| Week 26: Thyroid gland — Normal | 334 | 163 | 151 |
| Week 26: Thyroid gland — Abnormal, NCS | 3 | 2 | 0 |
| Week 26: Thyroid gland — Abnormal CS | 4 | 2 | 0 |
Dilated fundoscopy or fundus photography was performed by the investigator at screening (week -2) and week 26. The results of the examination were interpreted for each eye (left and right) and are categorised as normal, abnormal NCS or abnormal CS. Number of participants in each category at screening (week -2) and week 26 is presented.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Week -2: Left eye — Normal | 222 | 109 | 110 |
| Week -2: Left eye — Abnormal, NCS | 45 | 14 | 20 |
| Week -2: Left eye — Abnormal, CS | 91 | 52 | 50 |
| Week 26: Left eye — Normal | 217 | 99 | 100 |
| Week 26: Left eye — Abnormal, NCS | 39 | 20 | 13 |
| Week 26: Left eye — Abnormal, CS | 85 | 48 | 38 |
| Week -2: Right eye — Normal | 230 | 112 | 111 |
| Week -2: Right eye — Abnormal, NCS | 42 | 16 | 22 |
| Week -2: Right eye — Abnormal, CS | 86 | 47 | 47 |
| Week 26: Right eye — Normal | 217 | 103 | 96 |
| Week 26: Right eye — Abnormal, NCS | 40 | 23 | 15 |
| Week 26: Right eye — Abnormal, CS | 84 | 41 | 40 |
Electrocardiogram was assessed by the investigator as normal, abnormal NCS and abnormal CS. Number of participants at screening (week -2) and at week 26 is presented.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Week -2 — Normal | 223 | 109 | 108 |
| Week -2 — Abnormal, NCS | 94 | 46 | 52 |
| Week -2 — Abnormal CS | 41 | 20 | 20 |
| Week 26 — Normal | 227 | 108 | 87 |
| Week 26 — Abnormal, NCS | 76 | 47 | 40 |
| Week 26 — Abnormal CS | 38 | 12 | 24 |
Change in pulse from baseline (week 0) after 26 weeks of treatment is presented
| Beats per minuts (beats/min) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Pulse | 4.6 ± 8.6 | -0.1 ± 8.6 | 4.9 ± 9.7 |
Change in blood pressure (systolic and diastolic blood pressure) from baseline (week 0) after 26 weeks of treatment is presented
| Millimeters of mercury (mmHg) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Systolic blood pressure | -3.5 ± 12.7 | -1.2 ± 11.7 | -3.3 ± 13.8 |
| Distolic blood pressure | -0.4 ± 8.3 | -0.7 ± 8.1 | 0.0 ± 8.4 |
Change in alkaline phosphatase, ALT, AST, creatine kinase, amylase, lipase, creatine kinase serum from baseline (week 0) after 26 weeks of treatment is presented.
| Units per liter (U/L) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Alkaline phosphatase | -2.0 ± 14.85 | -2.29 ± 11.49 | -0.48 ± 14.11 |
| ALT | -4.63 ± 13.06 | -6.17 ± 13.54 | -2.81 ± 16.97 |
| AST | -1.31 ± 7.94 | -2.65 ± 8.40 | -0.99 ± 9.64 |
| Creatine kinase | 10.67 ± 100.87 | 15.37 ± 52.99 | 0.52 ± 56.20 |
| Amylase | 9.84 ± 36.73 | 5.09 ± 14.68 | 5.68 ± 13.70 |
| Lipase | 16.13 ± 101.19 | -1.87 ± 15.64 | 14.11 ± 19.76 |
Change in total protein, albumin serum from baseline (week 0) after 26 weeks of treatment is presented.
| grams per decileter (g/dL) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Albumin serum | -0.05 ± 0.28 | -0.09 ± 0.26 | 0.04 ± 0.26 |
| Total protein | -0.08 ± 0.42 | -0.08 ± 0.39 | -0.01 ± 0.39 |
Change in calcium serum (total), calcium corrected serum, potassium serum, sodium serum, urea serum from baseline (week 0) after 26 weeks of treatment is presented.
| mmol/L | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Calcium serum (total) | -0.01 ± 0.10 | -0.02 ± 0.10 | -0.00 ± 0.09 |
| Calcium corrected serum | -0.00 ± 0.08 | -0.00 ± 0.08 | -0.01 ± 0.07 |
| Sodium serum | 1.21 ± 2.09 | 0.98 ± 2.37 | 0.32 ± 2.12 |
| Urea serum | 0.05 ± 0.57 | 0.03 ± 0.53 | 0.16 ± 0.67 |
| Potassium serum | -0.04 ± 0.34 | -0.09 ± 0.39 | -0.04 ± 0.34 |
Change in total bilirubin serum, creatinine serum from baseline (week 0) after 26 weeks of treatment is presented.
| micromoles per liter (umol/L) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Total bilirubin | -0.78 ± 3.35 | -0.55 ± 4.52 | -1.16 ± 3.92 |
| creatinine serum | 1.02 ± 8.41 | 1.36 ± 7.92 | -0.60 ± 7.89 |
Change in erythrocyte blood from baseline (week 0) after 26 weeks of treatment is presented.
| 10^12 cells per liter (10^12/L) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Haematological Parameter: Erythrocytes Blood | -0.05 ± 0.27 | -0.00 ± 0.27 | -0.05 ± 0.25 |
Change in haematocrits from baseline (week 0) after 26 weeks of treatment is presented.
| Percentage points (%) of red blood cells | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Haematological Parameter: Haematocrits | -0.56 ± 2.65 | -0.49 ± 2.69 | -0.42 ± 2.57 |
Change in eosinophils from baseline after 26 weeks of treatment is presented.
| % of eosinophils | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Haemotological Parameter- Eosinophils | -0.06 ± 1.90 | 0.19 ± 1.73 | 0.11 ± 1.94 |
Change in neutrophils from baseline (week 0) after 26 weeks of treatment is presented.
| % of neutrophils | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Haematological Parameter - Neutrophils | 0.57 ± 6.46 | 0.18 ± 7.70 | -0.53 ± 7.05 |
Change in basophils from baseline (week 0) after 26 weeks of treatment is presented.
| % of basophils | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Haematological Parameter: Basophils | -0.02 ± 0.29 | -0.01 ± 0.28 | -0.03 ± 0.26 |
Change in monocytes from baseline (week 0) after 26 weeks of treatment is presented
| % of monocytes | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Haemotological Parameter- Monocytes | -0.03 ± 1.92 | 0.01 ± 1.85 | 0.05 ± 2.13 |
Change in lymphocytes from baseline (week 0) after 26 weeks of treatment is presented
| % of lymphocytes | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Haematological Parameter - Lymphocytes | -0.46 ± 6.04 | -0.38 ± 7.12 | 0.40 ± 6.11 |
Change in haemoglobin from baseline (week 0) after 26 weeks of treatment is presented.
| mmol/L | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Haematology: Haemoglobin Blood | -0.10 ± 0.53 | -0.06 ± 0.48 | -0.05 ± 0.47 |
Change in leukocytes from baseline (week 0) after 26 weeks of treatment
| 10^9 cells per liter (10^9/L) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Haematologcal Parameter: Leukocytes | 0.25 ± 1.18 | 0.23 ± 1.41 | -0.01 ± 1.14 |
Change in thrombocytes from baseline (week 0) after 26 weeks of treatment
| 10^9 cells per liter (10^9/L) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Change in Haematological Parameter: Thrombocytes | 8.19 ± 28.02 | 8.32 ± 34.48 | 4.32 ± 33.39 |
Calcitonin levels were measured and were categorised as low, normal or high in relation to reference range (8.31- 14.3 picogram/milliliter \[pg/mL\]). Number of participants in each category at baseline (week 0) and week 26 are presented.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Week 0 — Low | 0 | 0 | 0 |
| Week 0 — Normal | 351 | 172 | 178 |
| Week 0 — High | 7 | 3 | 2 |
| Week 26 — Low | 0 | 0 | 0 |
| Week 26 — Normal | 334 | 165 | 147 |
| Week 26 — High | 6 | 2 | 3 |
The urinalysis assessment was the measurements of protein, glucose, erythrocytes and ketones in urine at baseline (week 0) and week 26 and categorised as negative, trace and positive. Number of participants in each category at week 0 and week 26 is presented.
| Participants | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Week 0: Erythrocytes — Negative | 299 | 153 | 156 |
| Week 0: Erythrocytes — Trace | 36 | 16 | 16 |
| Week 0: Erythrocytes — Positive | 22 | 6 | 8 |
| Week 26: Erythrocytes — Negative | 297 | 146 | 136 |
| Week 26: Erythrocytes — Trace | 28 | 16 | 11 |
| Week 26: Erythrocytes — Positive | 14 | 5 | 4 |
| Week 0: Glucose — Negative | 253 | 119 | 123 |
| Week 0: Glucose — Trace | 35 | 19 | 18 |
| Week 0: Glucose — Positive | 69 | 37 | 39 |
| Week 26: Glucose — Negative | 322 | 157 | 131 |
| Week 26: Glucose — Trace | 11 | 3 | 5 |
| Week 26: Glucose — Positive | 6 | 7 | 15 |
| Week 0: Ketones — Negative | 325 | 152 | 167 |
| Week 0: Ketones — Trace | 25 | 20 | 11 |
| Week 0: Ketones — Positive | 7 | 3 | 2 |
| Week 26: Ketones — Negative | 334 | 163 | 141 |
| Week 26: Ketones — Trace | 4 | 3 | 10 |
| Week 26: Ketones — Positive | 1 | 1 | 0 |
| Week 0: Protein — Negative | 216 | 104 | 116 |
| Week 0: Protein — Trace | 86 | 40 | 37 |
| Week 0: Protein — Positive | 55 | 31 | 27 |
| Week 26: Protein — Negative | 254 | 120 | 105 |
| Week 26: Protein — Trace | 58 | 26 | 28 |
| Week 26: Protein — Positive | 27 | 21 | 18 |
This outcome measure is only applicable for the insulin degludec/liraglutide arm and insulin degludec arm. Serum samples were analysed for the presence of anti-insulin degludec specific antibodies. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (T).
| %B/T | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Occurence of Anti-insulin Degludec Specific Antibodies | 0.22 ± 1.02 | 0.12 ± 0.79 |
This outcome measure is only applicable for the insulin degludec/liraglutide arm and insulin degludec arm. Serum samples were analysed for the presence of cross-reacting antibodies to human insulin. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (T).
| %B/T | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Occurence of Antibodies Cross-reacting to Human Insulin | 6.61 ± 15.00 | 2.99 ± 10.89 |
This outcome measure is only applicable for the Insulin degludec/liraglutide arm and Insulin degludec arm. Serum samples were analysed for the presence of antobodies to human insulin. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (T).
| %B/T | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Occurence of Total Insulin Antibodies | 6.83 ± 15.78 | 3.11 ± 11.42 |
This outcome measure is applicable for the Insulin degludec/liraglutide arm and the liraglutide arm. Serum samples were analysed for the presence of anti-liraglutide antibodies. Number of participants who were assessed for anti-liraglutide antibodies at week 27 are presented.
| Participants | Insulin Degludec/Liraglutide | Liraglutide |
|---|---|---|
| Yes | 45 | 40 |
| No | 287 | 120 |
This outcome measure is applicable to the Insulin degludec/liraglutide arm and the liraglutide arm. Serum samples were analysed for the presence of cross-reacting antibodies to native GLP-1. Number of participants who measured with anti-liraglutide antibodies cross reacting native GLP-1 at week 27 are presented.
| Participants | Insulin Degludec/Liraglutide | Liraglutide |
|---|---|---|
| Occurence of Antibodies Cross-reacting to Native Glucagon-like Peptide (GLP-1) | 6 | 3 |
This outcome measure is only applicable for the Insulin degludec/liraglutide arm and liraglutide arm. Neutralising antibodies were assessed when the corresponding anti-Liraglutide antibody were positive at week 27. Number of participants who measured with neutralising liraglutide antibodies at week 27 are presented.
| Participants | Insulin Degludec/Liraglutide | Liraglutide |
|---|---|---|
| Occurence of Neutralising Liraglutide Antibodies | 9 | 8 |
This outcome measure is only applicable for the Insulin degludec/liraglutide arm and liraglutide arm. Cross reacting antibodies were assessed when anti-liraglutide antibody was positive. Number of participants who measured with neutralising liraglutide antibodies cross-reacting to native GLP-1 at week 27 are presented.
| Participants | Insulin Degludec/Liraglutide | Liraglutide |
|---|---|---|
| Occurence of Neutralising Antibodies Cross-reacting to Native GLP-1 | 0 | 0 |
This outcome measure is applicable for Insulin degludec and Insulin degludec/liraglutide arms. Serum samples from the Insulin degludec/liraglutide and Insulin degludec arms were assayed using population PK analysis. The maximum serum concentrations (Cmax) are summarised for the two arms.
| pmol/L | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Serum Concentrations of Insulin Degludec | 3583 ± 55.9 | 4133 ± 52.8 |
This outcome measure is for Insulin degludec/liraglutide and liraglutide arms. Serum samples from the Insulin degludec/liraglutide and liraglutide arms were assayed using population PK analysis. The Cmax are summarised for the two arms.
| pmol/L | Insulin Degludec/Liraglutide | Liraglutide |
|---|---|---|
| Plasma Concentration of Liraglutide | 9963 ± 50.4 | 21602 ± 37 |
Collected over Weeks 0-30. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Insulin Degludec/Liraglutide | 0/358 (0%) | 14/358 (3.9%) | 161/358 (45%) |
| Insulin Degludec | 0/175 (0%) | 7/175 (4%) | 55/175 (31.4%) |
| Liraglutide | 0/180 (0%) | 14/180 (7.8%) | 98/180 (54.4%) |
| Event | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Cerebral infarctionNervous system disorders | 1/358 | 0/175 | 3/180 |
| Angina unstableCardiac disorders | 2/358 | 1/175 | 0/180 |
| Cataract operationSurgical and medical procedures | 0/358 | 1/175 | 0/180 |
| Chronic gastritisGastrointestinal disorders | 0/358 | 1/175 | 0/180 |
| Deafness neurosensoryEar and labyrinth disorders | 0/358 | 1/175 | 0/180 |
| Diabetes mellitus inadequate controlMetabolism and nutrition disorders | 0/358 | 1/175 | 0/180 |
| Dupuytren's contractureMusculoskeletal and connective tissue disorders | 0/358 | 1/175 | 0/180 |
| Foot fractureInjury, poisoning and procedural complications | 0/358 | 1/175 | 0/180 |
| TinnitusEar and labyrinth disorders | 0/358 | 1/175 | 0/180 |
| Appendicitis perforatedInfections and infestations | 0/358 | 0/175 | 1/180 |
| Event | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Upper respiratory tract infectionInfections and infestations | 66/358 | 31/175 | 18/180 |
| Decreased appetiteMetabolism and nutrition disorders | 13/358 | 2/175 | 26/180 |
| DiarrhoeaGastrointestinal disorders | 23/358 | 3/175 | 26/180 |
| Lipase increasedInvestigations | 27/358 | 5/175 | 22/180 |
| NauseaGastrointestinal disorders | 14/358 | 1/175 | 21/180 |
| Diabetic retinopathyEye disorders | 28/358 | 6/175 | 10/180 |
| Gastrointestinal disorderGastrointestinal disorders | 1/358 | 0/175 | 10/180 |
| HyperlipidaemiaMetabolism and nutrition disorders | 16/358 | 6/175 | 10/180 |
| NasopharyngitisInfections and infestations | 16/358 | 9/175 | 5/180 |
| Abdominal discomfortGastrointestinal disorders | 1/358 | 0/175 | 9/180 |
FAS included all randomised participants.
| Age, Continuous(years) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide | Total |
|---|---|---|---|---|
| Mean | 54.5 ± 10.3 | 55.7 ± 10.2 | 54.1 ± 10.2 | 54.7 ± 10.3 |
| Sex/Gender, Customized(Participants) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide | Total |
|---|---|---|---|---|
| Female | 142 | 79 | 72 | 293 |
| Male | 219 | 100 | 108 | 427 |
| Ethnicity (NIH/OMB)(Participants) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide | Total |
|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 361 | 179 | 180 | 720 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 361 | 179 | 180 | 720 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 |
| White | 0 | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Glycosylated haemoglobin (HbA1c)(Percentage points of HbA1c) | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide | Total |
|---|---|---|---|---|
| Mean | 8.20 ± 0.83 | 8.31 ± 0.84 | 8.21 ± 0.77 | 8.23 ± 0.82 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes
This study is completed, as verified in Nov 2022. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Novo Nordisk A/S