Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted globally. The aim of this trial is to investigate efficacy and safety of semaglutide once-weekly versus placebo in drug-naïve subjects with type 2 diabetes. (SUSTAIN™ 1-Monotherapy).
Interventions
DRUGsemaglutide
Once weekly, administrated subcutaneously (s.c. under the skin)
DRUGplacebo
Once weekly, administrated subcutaneously (s.c. under the skin)
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- For Japan only: Male or female, age above or equal to 20 years at the time of signing inform consent - Subjects diagnosed with type 2 diabetes and treated with diet and exercise for at least 30 days before screening - HbA1c 7.0 - 10.0 % (53 - 86 mmol/mol) (both inclusive)
Exclusion criteria
- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice) throughout the trial including the 5 week follow-up period. United Kingdom: Adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), male sterilisation (where partner is sole partner of subject), or true abstinence (when in line with preferred and usual lifestyle) - Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol - Treatment with any glucose lowering agent(s) in a period of 90 days prior to screening. An exception is short-term treatment (no longer than 7 days in total) with insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value above or equal to 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired renal function defined as eGFR (estimated glomerular filtration rate ) below 30 mL/min/1.73 m\^2 per modification of diet in renal disease (MDRD) formula (4 variable version) - Acute coronary or cerebrovascular event within 90 days before randomisation - Heart failure, New York Heart Association class IV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c (Glycosylated Haemoglobin) | Week 0, week 30 | Change from baseline (week 0) in HbA1c was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight | Week 0, week 30 | Change from baseline (week 0) in body weight was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. |
| Change in Fasting Plasma Glucose (FPG) | Week 0, week 30 | Change from baseline (week 0) in FPG was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. |
| Change in Systolic and Diastolic Blood Pressure | Week 0, week 30 | Change from baseline (week 0) in systolic and diastolic blood pressure was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. |
| Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target | At 30 weeks of treatment | Percentage of subjects who achieve (yes/no): HbA1c below 7.0% (53 mmol/mol) American Diabetes Association target after 30 weeks' treatment. Missing HbA1c data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. |
| Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target | At 30 weeks of treatment | Percentage of subjects who achieve (yes/no): HbA1c below 6.5% (48 mmol/mol) American Diabetes Association target after 30 weeks' treatment. Missing HbA1c data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. |
Countries
Canada, Italy, Japan, Mexico, Romania, Russia, South Africa, United Kingdom, United States
Participant flow
Recruitment details
Out of 87 sites, selected for recruitment, 72 sites in 8 countries randomised subjects: Canada: 7 sites; Italy: 6 sites; Japan: 5 sites; Mexico: 2 sites; Russian Federation: 8 sites; South Africa: 8 sites; United Kingdom: 4 sites; United States: 32 sites.
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide 0.5 mg Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks followed by 0.5 mg semaglutide once weekly s.c. injections for the remaining 26 weeks of the treatment period. | 128 |
| Semaglutide 1.0 mg Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks, 0.5 mg semaglutide once weekly s.c. injections for the next 4 weeks followed by 1.0 mg semaglutide once weekly s.c. injections for the remaining 22 weeks of the treatment period. | 130 |
| Placebo Subjects were randomised to either of the 2 placebo arms (i.e., semaglutide placebo 0.5 mg and semaglutide placebo 1.0 mg) and then pooled for data analysis.
1. Placebo 0.5 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks followed by 0.5 mg placebo once weekly s.c. injections for the remaining 26 weeks of the treatment period.
2. Placebo 1.0 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks, 0.5 mg placebo once weekly s.c. injections for the next 4 weeks followed by 1.0 mg placebo once weekly s.c. injections for the remaining 22 weeks of the treatment period. | 129 |
| Total | 387 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 2 | 7 |
| Overall Study | Missing follow-up information | 3 | 5 | 3 |
| Overall Study | Randomized but not exposed | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 54.6 Years STANDARD_DEVIATION 11.1 | 52.7 Years STANDARD_DEVIATION 11.9 | 53.9 Years STANDARD_DEVIATION 11 | 53.7 Years STANDARD_DEVIATION 11.3 |
| Body weight | 89.81 kilogram(s) STANDARD_DEVIATION 22.96 | 96.87 kilogram(s) STANDARD_DEVIATION 25.59 | 89.05 kilogram(s) STANDARD_DEVIATION 22.16 | 91.93 kilogram(s) STANDARD_DEVIATION 23.83 |
| Diastolic blood pressure | 79.52 mmHg STANDARD_DEVIATION 9.06 | 79.25 mmHg STANDARD_DEVIATION 8.52 | 79.14 mmHg STANDARD_DEVIATION 8.39 | 79.30 mmHg STANDARD_DEVIATION 8.64 |
| Fasting plasma glucose | 9.66 mmol/L STANDARD_DEVIATION 2.77 | 9.90 mmol/L STANDARD_DEVIATION 2.5 | 9.68 mmol/L STANDARD_DEVIATION 2.77 | 9.75 mmol/L STANDARD_DEVIATION 2.67 |
| Glycosylated haemoglobin (HbA1c) | 8.09 percentage of HbA1c STANDARD_DEVIATION 0.89 | 8.12 percentage of HbA1c STANDARD_DEVIATION 0.81 | 7.95 percentage of HbA1c STANDARD_DEVIATION 0.85 | 8.05 percentage of HbA1c STANDARD_DEVIATION 0.85 |
| Sex: Female, Male Female | 68 Participants | 50 Participants | 59 Participants | 177 Participants |
| Sex: Female, Male Male | 60 Participants | 80 Participants | 70 Participants | 210 Participants |
| Systolic blood pressure | 127.87 mmHg STANDARD_DEVIATION 13.15 | 128.89 mmHg STANDARD_DEVIATION 12.92 | 129.57 mmHg STANDARD_DEVIATION 13.5 | 128.78 mmHg STANDARD_DEVIATION 13.18 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 53 / 128 | 47 / 130 | 27 / 129 |
| serious Total, serious adverse events | 7 / 128 | 7 / 130 | 5 / 129 |
Outcome results
Primary
Change in HbA1c (Glycosylated Haemoglobin)
Change from baseline (week 0) in HbA1c was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time frame: Week 0, week 30
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.5 mg | Change in HbA1c (Glycosylated Haemoglobin) | -1.47 Percentage of HbA1c | Standard Deviation 1.02 |
| Semaglutide 1.0 mg | Change in HbA1c (Glycosylated Haemoglobin) | -1.56 Percentage of HbA1c | Standard Deviation 1.26 |
| Placebo | Change in HbA1c (Glycosylated Haemoglobin) | -0.00 Percentage of HbA1c | Standard Deviation 0.9 |
Comparison: For the primary HbA1c endpoint, superiority was planned to be tested for semaglutide 1.0 mg versus placebo. The post-baseline responses were analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.p-value: <0.000195% CI: [-1.81, -1.25]Mixed Models Analysis
Comparison: For the primary HbA1c endpoint, superiority was planned to be tested for semaglutide 0.5 mg versus placebo, if superiority for semaglutide 1.0 mg was concluded. The post-baseline responses were analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.p-value: <0.000195% CI: [-1.71, -1.15]Mixed Models Analysis
Secondary
Change in Body Weight
Change from baseline (week 0) in body weight was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time frame: Week 0, week 30
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.5 mg | Change in Body Weight | -3.68 kilogram(s) | Standard Deviation 4.03 |
| Semaglutide 1.0 mg | Change in Body Weight | -4.67 kilogram(s) | Standard Deviation 5.19 |
| Placebo | Change in Body Weight | -0.89 kilogram(s) | Standard Deviation 3.46 |
Secondary
Change in Fasting Plasma Glucose (FPG)
Change from baseline (week 0) in FPG was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time frame: Week 0, week 30
Population: Full analysis set. Number of subject analysed=subjects who contributed to the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.5 mg | Change in Fasting Plasma Glucose (FPG) | -2.41 mmol/L | Standard Deviation 2.55 |
| Semaglutide 1.0 mg | Change in Fasting Plasma Glucose (FPG) | -2.39 mmol/L | Standard Deviation 2.74 |
| Placebo | Change in Fasting Plasma Glucose (FPG) | -0.55 mmol/L | Standard Deviation 2.2 |
Secondary
Change in Systolic and Diastolic Blood Pressure
Change from baseline (week 0) in systolic and diastolic blood pressure was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time frame: Week 0, week 30
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 0.5 mg | Change in Systolic and Diastolic Blood Pressure | Systolic blood pressure | -2.29 mmHg | Standard Deviation 12.58 |
| Semaglutide 0.5 mg | Change in Systolic and Diastolic Blood Pressure | Diastolic blood pressure | -0.73 mmHg | Standard Deviation 6.88 |
| Semaglutide 1.0 mg | Change in Systolic and Diastolic Blood Pressure | Systolic blood pressure | -2.74 mmHg | Standard Deviation 11.58 |
| Semaglutide 1.0 mg | Change in Systolic and Diastolic Blood Pressure | Diastolic blood pressure | 0.22 mmHg | Standard Deviation 7.6 |
| Placebo | Change in Systolic and Diastolic Blood Pressure | Systolic blood pressure | -2.01 mmHg | Standard Deviation 11.23 |
| Placebo | Change in Systolic and Diastolic Blood Pressure | Diastolic blood pressure | 0.60 mmHg | Standard Deviation 7.59 |
Secondary
Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target
Percentage of subjects who achieve (yes/no): HbA1c below 7.0% (53 mmol/mol) American Diabetes Association target after 30 weeks' treatment. Missing HbA1c data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time frame: At 30 weeks of treatment
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 0.5 mg | Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target | Yes | 74.2 Percentage of subjects |
| Semaglutide 0.5 mg | Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target | No | 25.8 Percentage of subjects |
| Semaglutide 1.0 mg | Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target | Yes | 72.3 Percentage of subjects |
| Semaglutide 1.0 mg | Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target | No | 27.7 Percentage of subjects |
| Placebo | Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target | Yes | 24.8 Percentage of subjects |
| Placebo | Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target | No | 75.2 Percentage of subjects |
Secondary
Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target
Percentage of subjects who achieve (yes/no): HbA1c below 6.5% (48 mmol/mol) American Diabetes Association target after 30 weeks' treatment. Missing HbA1c data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time frame: At 30 weeks of treatment
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 0.5 mg | Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target | Yes | 59.4 Percentage of subjects |
| Semaglutide 0.5 mg | Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target | No | 40.6 Percentage of subjects |
| Semaglutide 1.0 mg | Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target | Yes | 60.0 Percentage of subjects |
| Semaglutide 1.0 mg | Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target | No | 40.0 Percentage of subjects |
| Placebo | Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target | Yes | 13.2 Percentage of subjects |
| Placebo | Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target | No | 86.8 Percentage of subjects |