Overweight or obesity Nutritional, Metabolic, Endocrine
Conditions
Interventions
There are initially five study arms
usual care, low-energy diet, Tirzepatide, low-energy diet with exercise and Tirzepatide with exercise. As this is an adaptive platform trial, interventions may be added or removed as the evidence deve
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Master Inclusion Criteria: 1. BMI of = 30.0 kg/m² OR 2, BMI = 27 to 6 months post-completion of long COVID rehabilitation. Exception from the master inclusion/exclusion for the long COVID cohort (these criteria do not apply to this cohort): 1. BMI = 27 to <30.0 kg/m2 (with at least one of the following weight-related comorbidities or risk factors: hypertension, dyslipidaemia, cardiovascular disease (e.g., stable heart failure), elevated HbA1c (5.7 - 9.9%), polycystic ovary syndrome, history of gestational diabetes, taking hypertensive medication or taking lipid-lowering medication. 2. Those failing exercise screening protocol, as defined within the standard operating procedure developed by the NIHR Leicester Biomedical Research Centre (e.g., chest discomfort with exertion). Sub-study 2 Additional criteria that outline inclusion for sub-study 2: 1. Male Sub-study 3 Additional criteria that outline inclusion for sub-study 3: 1. Safe to undertake a brain scan using magnetic resonance imaging (MRI) – the study team will determine this. 2. Able to read instructions on a TV screen without prescription glasses (contact lenses may be allowed). 3. Regularly consume Western European or Mediterranean-style foods. 4. No strict dietary requirements or food allergies (e.g., vegetarian, vegan, lactose intolerant, nut allergy).
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 14/10/2025: Master Exclusion Criteria Individuals will be excluded if they meet any of the following: 1. Currently or previously (within the past 90 days before screening) participating in a weight loss intervention or group. 2. Previous or planned (during the trial period) obesity treatment with surgery or a weight loss device. However, the following are allowed: (1) liposuction and/or abdominoplasty, if performed > 1 year before screening, (2) lap banding, if the band has been removed > 1 year before screening, (3) intragastric balloon, if the balloon has been removed > 1 year before screening or (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed > 1 year before screening. 3. Treatment with any medication for the specific purposes of weight loss within the past 90 days before screening. 4. Treatment with any GLP-1RA or DPP4 inhibitor therapies for glucose control or weight loss within the past 90 days before screening. 5. Hypersensitivity or allergy to GLP-1 agonists or their excipients. 6. Taking medication known to induce weight gain within the past 90 days before screening such as atypical antipsychotic and mood stabilizers 7. Other weight loss or gain therapy-specific contraindications as judged by the study clinician. 8. Glucocorticoid therapy (excluding topical, intraocular, intranasal, intraarticular, or inhaled preparations) within the past 90 days before screening, or have an active autoimmune abnormality that in the opinion of the trial clinician will require future treatment with systemic glucocorticoids. 9. Uncontrolled thyroid disease, defined as thyroid stimulating hormone (TSH) > 6.0 mIU/L or 160/100 at screening (Visit 0). 14. Active or untreated malignancy or in remission for less than 3 years. 15. Current or planned pregnancy, or breastfeeding. Planned pregnancy in this instance involves women of childbearing potential (see definition in section 6.3) actively trying to become pregnant or aiming to become pregnant within the next six months. 16. Stage 3b CKD, defined as eGFR <30 ml/min/1.73m² at screening (Visit 0). 17. Any of the following: myocardial infarction, stroke, diagnosed heart failure or arrhythmogenic cardiomyopathy, atrial fibrillation, a pacemaker or implantable cardioverter defibrillator or hospitalisation for other cardiac events within the past six months. 18. Documented or self-reported liver cirrhosis. 19. Current participation in another research study with investigational medical products. 20. Serious illness with life expectancy < 1 year or other significant illness or disability which, in the opinion of the principal investigator or study clinician, precludes involvement. 21. Individuals with acute pancreatitis or a history of chronic pancreatitis. 22. Have a history of active or unstable Major Depressive Disorder (MDD) or other severe psychiatric disorder (e.g. schizophrenia, bipolar disorder) within the last 2 years. Patients with MDD or a generalized anxiety disorder whose disease state is considered stable may be considered for inclusion if they are not on excluded medications. 23. Pe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Physical function measured using meters covered during the incremental shuttle walk test at baseline and week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| The following secondary outcomes will be measured at baseline, and 12, 24, 52 and 104 weeks unless otherwise specified: 1. Physical function measured using meters covered during the incremental shuttle walk test 2. Cardiorespiratory fitness measured using maximal exercise test 3. Lower limb strength measured using BIODEX 4. Physical function measured using the Short Physical Performance Battery (SPPB) 5. Physical function measured using handgrip strength 6. Physical function measured using the World Health Organisation Disability Assessment Schedule (WHODAS 2.0) 7. Frailty measured using Fried’s Frailty Phenotype (FFP) 8. Fat mass, appendicular and whole-body lean body mass (LBM), and bone mineral density (BMD) measured using DEXA 9. Body composition measured using waist circumference, body weight, height and body mass index (BMI) 10. Muscle architecture measured using ultrasound 11. Resting energy expenditure measured using indirect calorimetry 12. Glycemic control measured using fasting glucose and insulin measured through venous blood sampling 13. Glycemic control measured using continuous glucose monitoring 14. Dyslipidaemia measured using a lipid profile assessed through venous blood sampling. 15. Blood pressure measure using an automated sphygmomanometer 16. Diet measured using a 24-hour diet recall interview and Diet Quality Questionnaire (DQQ) 17. Physical activity measured using a wrist-worn accelerometer, general practice physical activity questionnaire (GPPAQ), physical activity vital signs (PAVS), and international physical activity questionnaire (IPAQ) 18. Sedentary behaviour measured using a wrist-worn accelerometer, general practice physical activity questionnaire (GPPAQ), and international physical activity questionnaire (IPAQ) 19. Sleep measured using a wrist-worn accelerometer 20. Sleep quality measured using the Pittsburgh sleep quality index, self-reported sleep, and wrist-worn accelerometer 21. Anxiety and depression measured using the Patient | — |
Countries
England, United Kingdom
Outcome results
None listed