Type 2 diabetes and obesity Nutritional, Metabolic, Endocrine
Conditions
Interventions
Current interventions as of 16/02/2026:
This study aims to investigate whether a structured exercise training programme combined with a Meal Replacement Product (MRP)-based Low Energy Diet (LED) minim
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Age
40 Years to 65 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 16/02/2026: 1. South Asian ethnicity (Self-declared ethnicity of self) 2. Men and women 3. Aged =40 and =65 years, 4. A clinically coded diagnosis of type 2 diabetes between 3 months and 10 years previously 5. HbA1c 6.5% (48 mmol/mol) to 10% (86 mmol/mol) if not taking glucose-lowering medication; 6% (42 mmol/mol) to 10% (86 mmol/mol) if taking glucose-lowering medication 6. Body Mass Index =25 and =45 kg/m2 7. Self-reported stable weight over the previous 6 months (<+/-5% of bodyweight) 8. Treatment stable; no significant change to glucose-lowering regimen in the preceding 3 months, as determined by a study investigator 9. Able to provide informed consent 10. Able to understand written and spoken English or willing to use the University Hospitals of Leicester professional interpreter service 11. Able to take part in structured exercise training requiring the lower limbs (e.g., able to walk without assists or impairment) 12. Willingness and availability to participate in the proposed interventions to which they may be assigned, including attendance of intervention visits such as exercise sessions and adoption of Low Energy Diet which requires abstinence from alcohol 13. Willingness to self-monitor glucose, blood pressure and weight Previous inclusion criteria: 1. South Asian ethnicity (Self-declared ethnicity of self) 2. Men and women 3. Aged =40 and =65 years, 4. A clinically coded diagnosis of type 2 diabetes between 3 months and 10 years previously 5. HbA1c 6.5% (48 mmol/mol) to 10% (86 mmol/mol) if not taking glucose-lowering medication; 6% (42 mmol/mol) to 10% (86 mmol/mol) if taking glucose-lowering medication 6. Body Mass Index =27.5 and =45 kg/m2 7. Self-reported stable weight over the previous 6 months (<+/-5% of bodyweight) 8. Treatment stable; no significant change to glucose-lowering regimen in the preceding 3 months, as determined by a study investigator 9. Able to provide informed consent 10. Able to understand written and spoken English or willing to use the University Hospitals of Leicester professional interpreter service 11. Able to take part in structured exercise training requiring the lower limbs (e.g., able to walk without assists or impairment) 12. Willingness and availability to participate in the proposed interventions to which they may be assigned, including attendance of intervention visits such as exercise sessions and adoption of Low Energy Diet which requires abstinence from alcohol 13. Willingness to self-monitor glucose, blood pressure and weight
Exclusion criteria
Exclusion criteria: 1. Individuals with type 1, gestational or monogenic diabetes mellitus 2. On insulin therapy (NOTE: No COMBINE participant will be on insulin at baseline as this is an exclusion criterion. An exception may made for women who are on insulin because of its lack of teratogenic effects rather than because of the inability to control glycaemia on oral agents alone) 3. Drugs or conditions thought by the investigators to have a significant impact on the study protocol or outcomes 4. Serum alanine transaminase level >2.5-fold above the upper limit of the reference range 5. eGFR <45 ml.min-1 per 1.73m2 6. Currently participating in a weight reduction program in addition to routine care 7. Previous bariatric surgery 8. Currently on oral or injected steroids 9. Currently on weight loss medications (not including glucose-lowering medication) 10. Conditions that could impact weight (i.e., active malignancy/treatment in the past year, pregnancy, lactation, planning to become pregnant in the next 8 months) 11. Individuals with a self-reported or diagnosed eating disorder 12. Self-reported milk protein allergy or other allergy or dietary practice that prohibits the use of meal replacement products 13. Previous myocardial infarction, stroke, amputation secondary to type 2 diabetes/peripheral vascular disease, or admission due to cardiovascular disease-related event within 12 months 14. Previous clinically diagnosed atrial fibrillation 15. Previous clinically diagnosed heart failure 16. Pacemaker or implantable cardioverter defibrillator (ICD) 17. Substance abuse. The requirement for alcohol abstinence during the initial 12 weeks will make it unlikely that individuals with alcohol dependence will enrol. Substance abuse will be queried. 18. Presenting with cardiac abnormalities during the exercise electrocardiogram test (inclusive of very high blood pressure) 19. Currently receiving or requiring active treatment for retinopathy. 20. Current participation in another research study with investigational medical product 21. Severe Intolerance or unwillingness/inability to undertake Mixed Meal Tolerance Test (Severity of intolerance to be assessed by a member of the research team during screening visit)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Differences in the change of Lean Body Mass between groups measured using Dual-Energy X-ray Absorptiometry at baseline and 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Physiological: 1. Anthropometry and body composition (including total body weight, Body Mass Index, waist circumference, fat mass, and appendicular lean mass) measured using Dual-Energy X-ray Absorptiometry at baseline and week 12 2. Cross-sectional area of muscle, echo intensity (indication of intermuscular adipose tissue), fibre pennation angle, muscle and subcutaneous fat thickness, and volume of lower limb muscles such as the rectus femoris (quadriceps) measured using ultrasound imaging probe at baseline and week 12 3. Aerobic capacity (peak oxygen uptake; VO2peak) (to include absolute VO2peak (L·min-1) and VO2peak relative to lean body mass (LBM) (i.e., ml·kg LBM-1·min-1) and relative to overall body mass (ml·kg BW-1·min-1)) measured using graded treadmill maximal exercise test at baseline and week 12 4. Physical function measured using the Short Physical Performance Battery (SPPB) and sit-to-stand 60 at baseline and week 12 5. Hand grip and lower body strength measured using a hand dynamometer and BIODEX at baseline and week 12 6. Resting metabolic rate (RMR) measured using indirect calorimetry at baseline and week 12 Cardiometabolic: 7. Fasting and post-prandial markers of glucose, insulin and C-peptide in response to a Mixed Meal Tolerance Test at baseline and week 12 8. Mean glucose levels, glucose variability (standard deviation and coefficient of variation), time in ranges above and below range measured using continuous glucose monitoring 9. The proportion of participants achieving diabetes remission defined as HbA1c <6.5% (48mmol/mol) without prescribed glucose-lowering medications between baseline and 12 weeks of the study period 10. Cardiometabolic risk factors, such as blood lipid profile (including total cholesterol, HDL, LDL and triglycerides), urine albumin to creatinine ratio (ACR) and systolic and diastolic blood pressure at baseline and week 12 Behavioural: 11. Device-measured sleep, sedentary time and physical activity measured using a wrist- | — |
Countries
England, United Kingdom
Contacts
Public ContactFranciskos Arsenyadis
Outcome results
None listed