Diabetes Mellitus, Type 2
Conditions
Brief summary
This study compares how three doses of semaglutide work in participants with type 2 diabetes (T2D) and overweight who are taking metformin. The study will look mainly at how well participant's blood sugar and participant's body weight are controlled when they are taking the study medicine at different doses. Participants will either get semaglutide \[2 milligrams (mg), 8 mg, or 16 mg\] or semaglutide placebo (a dummy medicine). Participants will take the study medicine with an injection pen called NovoPen®4. The injection pen is a medical tool with a needle used to inject the study medicine under the skin. The study will last for about 52 weeks. Participants will have 13 clinic visits and 4 phone calls.
Interventions
DRUGSemaglutide
Semaglutide s.c. injection once-weekly for 40 weeks. Dose gradually increased over 24 weeks, followed by a 16 week maintenance period.
DRUGPlacebo
Semaglutide placebo s.c. injection once-weekly for 40 weeks. Dose gradually increased over 24 weeks, followed by a 16 week maintenance period.
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 64 Years
Healthy volunteers
No
Inclusion criteria
* Male or female. * Aged 18-64 years (both inclusive) at the time of signing informed consent. * Diagnosed with type 2 diabetes mellitus greater than equal to (≥) 180 days prior to the day of screening. * Glycosylated haemoglobin (HbA1c) of 7.0 - 10.5 percentage (%) \[53 - 91 millimoles per mole (mmol/mol)\] (both inclusive). * Body Mass Index (BMI) ≥ 27.0 kilograms per meter square (kg/m\^2). * Stable daily dose(s) ≥ 90 days prior to the day of screening of any metformin formulations.
Exclusion criteria
* Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes. * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to day of 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. * Renal impairment measured as estimated glomerular filtration rate (eGFR) value of less than (\<) 30 milliliters per minute (mL/min)/1.73 meter square (m\^2) at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycated Haemoglobin (HbA1c) | Baseline (week 0) and End of treatment (week 40) | Change in HbA1c from baseline (week 0) to end of treatment (week 40) is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight | Baseline (week 0) and End of treatment (week 40) | Change in body weight from baseline (week 0) to end of treatment (week 40) is presented. |
| Number of Treatment-emergent Adverse Events (TEAEs) | From baseline (week 0) up to end of study (week 49) | An adverse event (AE) is any untoward medical occurrence in a clinical study participant that is temporally associated with use of investigational medicinal products (IMP), whether or not considered related to IMP. AE can therefore be any unfavourable & unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with use of IMP. TEAE was defined as event that had onset date (or increase in severity) during on-treatment observation period. On treatment observation period data are presented. On-treatment observation period is defined as time points from first drug date until first date of end of data point sets (DPS1) or last administration of randomised treatment +63 days. DPS1 in trial is defined as all observed data points from randomisation until first date of end of study visit or date of death or date of withdrawal of informed consent or contact as defined by investigator for participants that are lost to follow up. |
| Number of Treatment-emergent Severe Hypoglycaemic Episodes | From baseline (week 0) up to end of study (week 49) | Number of treatment-emergent severe Hypoglycaemic episodes are presented. Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. On treatment observation period data are presented. On-treatment oberservation period is defined as time points from first drug date until the first date of end of data point sets (DPS1) or last administration of randomised treatment +63 days. DPS1 in trial is defined as all observed data points from randomisation until the first date of end of study visit or date of death or date of withdrawal of informed consent or date of last contact as defined by investigator for participants that are lost to follow up. |
Countries
Greece, Hungary, Poland, Puerto Rico, United States
Participant flow
Recruitment details
This study was conducted at 82 active sites in 4 countries, of which 75 sites enrolled participants.
Pre-assignment details
Participants were randomized at a ratio of 3:1:3:1:3:1 to receive semaglutide (2 milligram \[mg\], 8 mg, 16 mg) or matching placebo.
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide 2.0 mg Participants received once-weekly subcutaneous (s.c.) injections of semaglutide (in a dose-escalation manner every 4 weeks \[0-4 weeks: 0.29 mg; 5-8 weeks: 0.58 mg; 9-12 weeks: 1.06 mg\], followed by the maintenance dose of 2 mg) till 40 weeks. | 61 |
| Semaglutide 8.0 mg Participants received once-weekly s.c. injections of semaglutide (in a dose-escalation manner every 4 weeks \[0-4 weeks: 0.29 mg; 5-8 weeks: 0.58 mg; 9-12 weeks: 1.06 mg; 13-16 weeks: 2.02 mg; 17-20 weeks: 4.03 mg\], followed by the maintenance dose of 8 mg) till 40 weeks. | 62 |
| Semaglutide 16.0 mg Participants received once-weekly s.c. injections of semaglutide (in a dose-escalation manner every 4 weeks \[0-4 weeks: 0.29 mg; 5-8 weeks: 0.58 mg; 9-12 weeks: 1.06 mg; 13-16 weeks: 2.02 mg; 17-20 weeks: 4.03 mg; 21-24 weeks: 8.06 mg\], followed by the maintenance dose of 16 mg) till 40 weeks. | 62 |
| Placebo Participants received once-weekly s.c. injection of placebo matched to semaglutide for 40 weeks. | 60 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Failure to meet randomization criteria | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 2 | 2 | 2 |
| Overall Study | Physician Decision | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 5 | 4 | 3 |
Baseline characteristics
| Characteristic | Semaglutide 2.0 mg | Semaglutide 8.0 mg | Semaglutide 16.0 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 52.3 years STANDARD_DEVIATION 7.6 | 53.7 years STANDARD_DEVIATION 7.5 | 52.9 years STANDARD_DEVIATION 8.6 | 52.1 years STANDARD_DEVIATION 9.5 | 52.8 years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 8 Participants | 9 Participants | 13 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 54 Participants | 53 Participants | 47 Participants | 206 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 11 Participants | 4 Participants | 4 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 54 Participants | 49 Participants | 56 Participants | 55 Participants | 214 Participants |
| Sex: Female, Male Female | 27 Participants | 33 Participants | 25 Participants | 35 Participants | 120 Participants |
| Sex: Female, Male Male | 34 Participants | 29 Participants | 37 Participants | 25 Participants | 125 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 60 | 0 / 62 | 0 / 59 |
| other Total, other adverse events | 30 / 60 | 48 / 60 | 50 / 62 | 29 / 59 |
| serious Total, serious adverse events | 4 / 60 | 2 / 60 | 1 / 62 | 2 / 59 |
Outcome results
Primary
Change in Glycated Haemoglobin (HbA1c)
Change in HbA1c from baseline (week 0) to end of treatment (week 40) is presented.
Time frame: Baseline (week 0) and End of treatment (week 40)
Population: Full analysis set included all randomised participants. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.0 mg | Change in Glycated Haemoglobin (HbA1c) | -1.9 Percentage-point of HbA1c | Standard Deviation 1.1 |
| Semaglutide 8.0 mg | Change in Glycated Haemoglobin (HbA1c) | -1.8 Percentage-point of HbA1c | Standard Deviation 1.5 |
| Semaglutide 16.0 mg | Change in Glycated Haemoglobin (HbA1c) | -2.1 Percentage-point of HbA1c | Standard Deviation 1.5 |
| Placebo | Change in Glycated Haemoglobin (HbA1c) | -1.1 Percentage-point of HbA1c | Standard Deviation 1.3 |
p-value: 0.000295% CI: [-1.25, -0.39]ANCOVA
p-value: 0.000395% CI: [-1.19, -0.35]ANCOVA
p-value: <0.000195% CI: [-1.5, -0.64]ANCOVA
Comparison: The change in HbA1c from baseline was analysed using an ANCOVA (Analysis of Covariance) with randomised treatment and stratification factor, sex as fixed effect and baseline HbA1c as a covariate. Missing values were imputed using Jump to reference method.p-value: 0.830595% CI: [-0.38, 0.47]ANCOVA
p-value: 0.167895% CI: [-0.72, 0.13]ANCOVA
p-value: 0.244595% CI: [-0.67, 0.17]ANCOVA
Secondary
Change in Body Weight
Change in body weight from baseline (week 0) to end of treatment (week 40) is presented.
Time frame: Baseline (week 0) and End of treatment (week 40)
Population: Full analysis set included all randomised participants. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.0 mg | Change in Body Weight | -8.9 Kilogram (kg) | Standard Deviation 8.5 |
| Semaglutide 8.0 mg | Change in Body Weight | -10.1 Kilogram (kg) | Standard Deviation 7.4 |
| Semaglutide 16.0 mg | Change in Body Weight | -13.1 Kilogram (kg) | Standard Deviation 8.4 |
| Placebo | Change in Body Weight | -2.3 Kilogram (kg) | Standard Deviation 4.9 |
Secondary
Number of Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant that is temporally associated with use of investigational medicinal products (IMP), whether or not considered related to IMP. AE can therefore be any unfavourable & unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with use of IMP. TEAE was defined as event that had onset date (or increase in severity) during on-treatment observation period. On treatment observation period data are presented. On-treatment observation period is defined as time points from first drug date until first date of end of data point sets (DPS1) or last administration of randomised treatment +63 days. DPS1 in trial is defined as all observed data points from randomisation until first date of end of study visit or date of death or date of withdrawal of informed consent or contact as defined by investigator for participants that are lost to follow up.
Time frame: From baseline (week 0) up to end of study (week 49)
Population: Safety analysis set included all participants who are exposed to randomised treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 2.0 mg | Number of Treatment-emergent Adverse Events (TEAEs) | 43 Events |
| Semaglutide 8.0 mg | Number of Treatment-emergent Adverse Events (TEAEs) | 54 Events |
| Semaglutide 16.0 mg | Number of Treatment-emergent Adverse Events (TEAEs) | 55 Events |
| Placebo | Number of Treatment-emergent Adverse Events (TEAEs) | 37 Events |
Secondary
Number of Treatment-emergent Severe Hypoglycaemic Episodes
Number of treatment-emergent severe Hypoglycaemic episodes are presented. Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. On treatment observation period data are presented. On-treatment oberservation period is defined as time points from first drug date until the first date of end of data point sets (DPS1) or last administration of randomised treatment +63 days. DPS1 in trial is defined as all observed data points from randomisation until the first date of end of study visit or date of death or date of withdrawal of informed consent or date of last contact as defined by investigator for participants that are lost to follow up.
Time frame: From baseline (week 0) up to end of study (week 49)
Population: Safety analysis set included all participants who are exposed to randomised treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 2.0 mg | Number of Treatment-emergent Severe Hypoglycaemic Episodes | 0 Episodes |
| Semaglutide 8.0 mg | Number of Treatment-emergent Severe Hypoglycaemic Episodes | 0 Episodes |
| Semaglutide 16.0 mg | Number of Treatment-emergent Severe Hypoglycaemic Episodes | 0 Episodes |
| Placebo | Number of Treatment-emergent Severe Hypoglycaemic Episodes | 0 Episodes |