Diabetes Mellitus, Type 2, Obesity
Conditions
Brief summary
This study will look at how much weight participants will lose and how much blood sugar control they achieve from the start to the end of the study. The weight loss in participants taking the investigational high dose of semaglutide will be compared to the weight loss in people taking "dummy" medicine and a lower dose of semaglutide. In addition to taking the medicine, participants will have talks with study staff about healthy food choices and how to be more physically active. Participants will either get semaglutide or "dummy" medicine. Which treatment participants get is decided by chance. Participants are more likely (4 out of 5) to get semaglutide than the "dummy" medicine. The study medicine will be injected briefly, under skin, with a thin needle, typically in the stomach, thighs, or upper arms. After receiving first dose, the dose of semaglutide will be gradually increased until reaching the target dose. The study will last for about 1.5 years
Interventions
DRUGSemaglutide
Participants will receive once-weekly s.c. injections of semaglutide in escalating doses (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, 2.4 mg and 7.2 mg) every fourth week. Treatment will be continued on the maintenance dose of 7.2 mg once-weekly for an additional 52 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.
DRUGPlacebo
Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female. * Age above or equal to 18 years at the time of signing informed consent. * BMI greater than or equal to 30.0 kilograms per square meter (kg/m\^2). * Diagnosed with type 2 diabetes (T2D) greater than or equal to 180 days prior to the day of screening. * History of at least one self-reported unsuccessful dietary effort to lose body weight. * HbA1c 7.0-10.0 percent (53-86 millimoles per mole \[mmol/mol\]) (both inclusive) as measured by central laboratory at screening.
Exclusion criteria
* A self-reported change in body weight greater than 5 kilograms (kg) (11 pounds \[lbs\]) within 90 days before screening irrespective of medical records. * Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. * Renal impairment with estimated Glomerular Filtration Rate (eGFR) less than 30 milliliters per minute per 1.73 square meter (30 mL/min/1.73 m\^2) (less than 45 mL/min/1.73 m\^2 in participants treated with Sodium-glucose Cotransporter-2 \[SGLT2i\]) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 by the central laboratory at screening. * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days before screening or in the period between screening and randomization. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change in Body Weight | Baseline (week 0), End of treatment (week 72) | Relative change in body weight from baseline (week 0) to end of treatment (week 72) is presented. |
| Number of Participants Who Achieve Body Weight Reduction Greater Than or Equal to (>=) 5% (Yes/no) | At week 72 | Number of participants who achieve body weight reduction \>=5% is presented. Yes defines participants who achieved body weight reduction \>= 5% and No defines participants who did not achieve body weight reduction \>=5%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieve Body Weight Reduction >= 10% (Yes/no) | At week 72 | Number of participants who achieve body weight reduction \>=10% is presented. Yes defines participants who achieved body weight reduction greater than or equal to 10% and No defines participants who did not achieve body weight reduction greater than or equal to 10%. |
| Number of Participants Who Achieve Body Weight Reduction >= 15% (Yes/no) | At week 72 | Number of participants who achieve body weight reduction \>=15% is presented. Yes defines participants who achieved body weight reduction greater than or equal to 15% and No defines participants who did not achieve body weight reduction greater than or equal to 15%. |
| Number of Participants Who Achieve Body Weight Reduction >= 20% (Yes/no) | At week 72 | Number of participants who achieve body weight reduction \>=20% is presented. Yes defines participants who achieved body weight reduction greater than or equal to 20% and No defines participants who did not achieve body weight reduction greater than or equal to 20%. |
| Change in Waist Circumference | Baseline (week 0), End of treatment (week 72) | Change in waist circumference from baseline (week 0) to end of treatment (week 72) is presented. |
| Change in Glycated Haemoglobin (HbA1c) | Baseline (week 0), End of treatment (week 72) | Change in HbA1c from baseline (week 0) to end of treatment (week 72) is presented. |
| Change in Body Weight | Baseline (week 0), End of treatment (week 72) | Change in body weight from baseline (week 0) to end of treatment (week 72) is presented. |
| Change in Body Mass Index (BMI) | Baseline (week 0), End of treatment (week 72) | Change in BMI from baseline (week 0) to end of treatment (week 72) is presented. |
| Change in Systolic Blood Pressure | Baseline (week 0), End of treatment (week 72) | Change in systolic blood pressure from baseline (week 0) to end of treatment (week 72) is presented. |
| Change in Diastolic Blood Pressure | Baseline (week 0), End of treatment (week 72) | Change in diastolic blood pressure from baseline (week 0) to end of treatment (week 72) is presented. |
| Change in Total Cholesterol (Millimoles Per Liter [mmol/L]) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in total cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in Total Cholesterol (Milligrams Per Deciliter [mg/dL]) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in total cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in High-density Lipoprotein (HDL) Cholesterol (mmol/L) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in HDL cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in HDL Cholesterol (mg/dL) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in HDL cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in Low-density Lipoprotein (LDL) Cholesterol (mmol/L) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in LDL cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in LDL Cholesterol (mg/dL) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in LDL cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in Very-low-density Lipoprotein (VLDL) Cholesterol (mmol/L) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in VLDL cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in VLDL Cholesterol (mg/dL) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in VLDL cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in Triglycerides (mmol/L) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in triglycerides in mmol/L from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in Triglycerides (mg/dL) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in triglycerides in mg/dL from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in Free Fatty Acids (mmol/L) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in free fatty acids in mmol/L from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in Free Fatty Acids (mg/dL) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in free fatty acids in mg/dL from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in High-sensitivity C-reactive Protein (hsCRP) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in hsCRP in mg/L from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in Fasting Plasma Glucose | Baseline (week 0), End of treatment (week 72) | Change in fasting plasma glucose from baseline (week 0) to end of treatment (week 72) is presented. |
| Change in Fasting Serum Insulin (Picomoles Per Liter [Pmol/L]) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in fasting serum insulin in pmol/L from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Change in Fasting Serum Insulin (Milliinternational Units Per Milliliter [mIU/mL]) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in fasting serum insulin in mIU/ml from baseline (week 0) to end of treatment (week 72) as ratio to baseline is presented. |
| Number of Participants With HbA1c Less Than 7.0 % (53 Millimoles Per Mole [mmol/Mol]) | At week 72 | Number of participants with HbA1c less than 7.0 % (53 mmol/mol) at week 72 is presented. |
| Number of Participants With HbA1c Less Than or Equal to 6.5% (48 mmol/Mol) | At week 72 | Number of participants with HbA1c less than or equal to 6.5% (48 mmol/mol) at week 72 is presented. |
| Semaglutide 7.2 mg Versus Placebo: Number of Adverse Events (AEs) | At week 81 | Number of AEs is reported. An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. |
| Semaglutide 7.2 mg Versus Placebo: Number of Serious Adverse Events (SAEs) | At week 81 | Number of SAEs is reported. A SAE is any untoward medical occurrence that fulfils at least one of the following criteria: results in death, is life threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical event. |
| Change in Pulse | Baseline (week 0), End of treatment (week 72) | Change in pulse from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Placebo: Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes | At week 81 | Number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes is presented. |
| Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of AEs | At week 81 | Number of AEs is reported. An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of IMP, whether or not considered related to the IMP. |
| Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of SAEs | At week 81 | Number of SAEs is reported. A SAE is any untoward medical occurrence that fulfils at least one of the following criteria: results in death, is life threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical event. |
| Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes | At week 81 | Number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes is presented. |
Countries
Bulgaria, Canada, Hungary, Poland, Portugal, Slovakia, South Africa, United States
Contacts
STUDY_DIRECTORClinical Transparency (dept. 2834)
Novo Nordisk A/S
Participant flow
Recruitment details
The trial was conducted at 68 sites in 8 countries.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58 Years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 428 Participants |
| Sex: Female, Male Female | 265 Participants |
| Sex: Female, Male Male | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 307 | 1 / 103 | 1 / 102 |
| other Total, other adverse events | 187 / 307 | 64 / 103 | 40 / 102 |
| serious Total, serious adverse events | 30 / 307 | 11 / 103 | 10 / 102 |
Outcome results
None listed