Obesity, Diabetes, Metabolic Syndrome
Conditions
Keywords
obesity, diabetes, semaglutide
Brief summary
A double-blinded, randomised, placebo-controlled trial of semaglutide 3.0 mg/ml in patients with poor weight-loss following bariatric surgery. The primary aim of this trial is to determine whether, and the extent to which, 68 weeks of subcutaneous semaglutide 3.0 mg/ml causes greater percentage weight loss (%WL), reduction in adiposity, improvement in metabolic and inflammatory indices and health-related quality of life (HRQoL) than placebo, in patients with poor weight loss following gastric bypass or sleeve gastrectomy.
Interventions
DRUGSemaglutide 3 mg
Semaglutide 2.4 mg/week, subcutaneous injection. Treatment dose: 16 weeks of dose escalation + 52 weeks of study dose (i.e., 2.4 mg/week).
DRUGPlacebo
Placebo
Sponsors
University College, London
National Institute for Health Research, United Kingdom
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
double blinded: both participants and study doctors will be blind to group allocation
Intervention model description
Phase 3b, double-blinded, randomised, parallel group trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients, ≥1 year primary GB or primary SG, with poor weight-loss (\<20% WL) that is not caused by either a surgical or psychological problem. 2. Adults, 18-65 years inclusive. 3. Females of childbearing potential and female partners of male participants must be willing to use highly effective method of contraception (hormonal or barrier method of birth control; abstinence) (Appendix 2) from the time consent is signed until 2 months after treatment discontinuation. 4. Females of childbearing potential must have a negative pregnancy test within 7 days prior to randomisation. NOTE: Subjects are considered not of child bearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. 5. A self-reported ≤5 % variation in body weight over preceding 3 months. 6. Fluent in English and able to understand and complete questionnaires. 7. Participants capable to provide written informed consent and comply with the trial protocol.
Exclusion criteria
1. Bariatric surgical procedure other than GB and SG, or revision bariatric surgery of any operation type. 2. Personal history of type I diabetes or type II diabetes mellitus currently treated with insulin. 3. Concomitant use of GLP-1R agonist or DPPIV-inhibitors. 4. Female who is pregnant, breast-feeding, or intends to become pregnant. 5. Current participation in other clinical intervention trial. 6. History of suicidal attempt in the previous 5 years or untreated severe depression or mental health condition assessed by direct questioning. 7. Symptomatic gallstone disease 8. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg). 9. Renal impairment measured as glomerular infiltration rate (eGFR \<15 ml/min 1.73 m2 10. Known or suspected hypersensitivity to semaglutide or any of the excipients involved in their formulation. 11. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. 12. History of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed. 13. Personal history of acute pancreatitis 180 days before screening or chronic pancreatitis. 14. Uncontrolled thyroid disease. 15. History of stroke, unstable angina, acute coronary syndrome, congestive heart failure New York Heart Association class III-IV within the preceding 12 months. 16. Untreated clinically significant arrhythmias. 17. Diabetic gastroparesis. 18. Concomitant usage of medications that cause weight gain or weight loss. 19. Known or suspected abuse of alcohol or recreational drugs. 20. Severe hepatic impairment diagnosed via liver function blood tests and clinical evaluation 21. Any additional factor, which in the investigator's opinion, might jeopardise the subject's safety or compliance with the trial protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Weight Change | Baseline and week 68 | Weight change = \[(Weight at Visit 68 minus weight at baseline)/ weight at baseline\]\*100. Positive values represent weight gain and negative values represent weight loss. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systolic Blood Pressure and Diastolic Blood Pressure in Participants With Pre-existing Hypertension | Baseline to 68 weeks | Change in systolic and diastolic BP from baseline to 68 weeks in participants with pre-existing hypertension. Blood pressure change = Week 68 value minus Baseline value |
| HbA1c in Participants With Pre-existing Type 2 Diabetes | Baseline to 68 weeks | Change in HbA1c from baseline to 68 weeks in participants with pre-existing Type 2 Diabetes. HbA1c change = Week 68 value minus Baseline value |
| Change in Circulating HbA1c Levels in Participants With Pre-diabetes | Baseline to 68 weeks | Change in circulating HbA1c levels in participants with pre-diabetes from baseline to 68 weeks |
| Categorical Weight Loss | Baseline to 68 weeks | Cumulative percentage of participants who met the criteria for each weight loss threshold (\<10%, ≥10%, ≥15%, ≥20%) at 68 weeks |
| Body Mass Index (BMI) | Baseline to 68 weeks | Change in Body Mass Index from baseline to 68 weeks |
| Body Composition | Baseline to 68 weeks | Change in body composition (measured by Bioelectrical Impedance Analysis) from baseline to 68 weeks |
| Blood Pressure Change | Baseline to 68 weeks | Change in systolic and diastolic Blood Pressure from baseline to 68 weeks. Blood pressure change = Week 68 value minus Baseline value |
| Cardiovascular Outcome - Heart Rate | baseline to 68 weeks | Change in heart rate from baseline to 68 weeks |
| HbA1c | Baseline to 68 weeks | Change in HbA1c from baseline to 68 weeks |
| Lipid Profile | Baseline to 68 weeks | Mean changes in total cholesterol and triglycerides from baseline to 68 weeks |
| Change in IWQOL-Lite (Impact of Weight on Quality of Life) | Baseline to 68 weeks | The 'Impact of Weight on Quality of Life' is a 5 point Likert scale ranging from 1 = "Never true" to 5 = "Always true". It consist of five subscales (physical function, self-esteem, sexual life, public distress and work). Average scores are computed if a minimum of 50% of the items for each scale are answered, and for the total score only if 75% of all items are completed. The average score is multiplied by the total number of items for each scale. The total score is a mean of all available items averaged together. The averaged scores are then transformed and reversed, to be from 0 lowest (worst), to 100 highest (best) quality of life. The change in IQWOL-Lite scores from baseline to 68 weeks was calculated by week 68 score minus baseline score". |
| High-sensitivity C-reactive Protein (hsCRP) | Baseline to 68 weeks | Mean change in High-sensitivity C-reactive protein (hsCRP) from baseline to 68 weeks |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were recruited via Bariatric Clinics across 2 London hospitals between 1 November 2022 and 02 November 2023, with follow up of the final patient on 09 April 2025.
Pre-assignment details
128 participants were pre-screened for eligibility, 86 screened for eligibility, and of that 70 were eligible for randomisation.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 70 Participants |
| Age, Continuous | 47.3 years STANDARD_DEVIATION 10.3 |
| Body Mass Index | 41.5 kg/m^2 STANDARD_DEVIATION 6.5 |
| Bodyweight (kg) | 118.6 units on scale STANDARD_DEVIATION 23.3 |
| Diabetes status Normoglycemia/Pre-diabetes | 31 Participants |
| Diabetes status Type 2 diabetes | 3 Participants |
| Family history of obesity no | 19 Participants |
| Family history of obesity yes | 51 Participants |
| HbA1c | 37.1 Mmol/mol STANDARD_DEVIATION 5.6 |
| Procedure Type Gastric bypass | 8 Participants |
| Procedure Type Sleeve gastrectomy | 28 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Sex: Female, Male Female | 58 Participants |
| Sex: Female, Male Male | 7 Participants |
| Time Since Surgery | 88.6 months STANDARD_DEVIATION 50.5 |
| Weight change since day of surgery (to randomisation) | 7.5 percentage change STANDARD_DEVIATION 7.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 33 / 35 | 34 / 35 |
| serious Total, serious adverse events | 8 / 35 | 3 / 35 |
Outcome results
None listed