Diabetes mellitus Nutritional, Metabolic, Endocrine Diabetes mellitus
Conditions
Interventions
Current interventions as of 04/08/2025:
Initial screening checks will be conducted verbally via telephone prior to arranging each participant’s first visit (Visit 0). Consent for the main study and fu
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 30/08/2023: 1. Age 40 to 75 years, inclusive 2. Diagnosed T2DM, treated by lifestyle management alone or in combination with mono- or combination therapy with oral glucose-lowering pharmacological therapies (with exception of pre-defined exclusion criteria) 3. HbA1c =10.5% (<91 mmol/mol) 4. Historical evidence of functional limitation or frailty defined as at least one of : 4.1. Impaired physical function or frailty; SPPB score 1 to 10 (inclusive) recorded within the preceding 5 years 4.2. A coding of mild-to-moderate frailty based on the Electronic Frailty Index (eFI) within primary care 4.3. V02peak recorded within the preceding 5 years 4.3.1. Men <50 years: <30 mL/kg, Men 50+ years: <25 mL/kg 4.3.2. Women <50 years: <25 mL/kg, Women 50+ years: <22 mL/kg 4.4. SARC-F questionnaire score of 4 or more 4.5. BMI =25 kg/m² (= 22.5 kg/m² if of South Asian ethnicity) 4.6. Weight stable; <3 kg weight change in the preceding 3 months 4.7. Treatment stable; no significant change to glucose-lowering regimen in the preceding 3 months, as determined by a study investigator 4.8. Able and willing to give informed consent 4.9. Able to understand spoken English 4.10. Able to take part in structured exercise training (in the opinion of the Investigator) _____ Previous inclusion criteria: 1. Age 40 to 75 years, inclusive 2. Diagnosed T2DM, treated by lifestyle management alone or in combination with mono- or combination therapy with oral glucose-lowering pharmacological therapies (with exception of pre-defined exclusion criteria) 3. HbA1c 6.5 to 10% (47 to 86 mmol/mol), inclusive 4. Historical evidence of functional limitation or frailty defined as at least one of : 4.1. Impaired physical function or frailty; SPPB score 1 to 10 (inclusive) recorded within the preceding 5 years 4.2. A coding of mild-to-moderate frailty based on the Electronic Frailty Index (eFI) within primary care 4.3. V02peak =18 ml/kg recorded within the preceding 5 years 4.4. SARC-F questionnaire score of 4 or more 4.5. BMI =25 kg/m² (= 22.5 kg/m² if of South Asian ethnicity) 4.6. Weight stable; <3 kg weight change in the preceding 3 months 4.7. Treatment stable; no significant change to glucose-lowering regimen in the preceding 3 months, as determined by a study investigator 4.8. Able and willing to give informed consent 4.9. Able to understand spoken English 4.10. Able to take part in structured exercise training (in the opinion of the Investigator)
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 04/08/2025: 1. Individuals with type 1, gestational or monogenic diabetes mellitus 2. eGFR <60 ml/min per 173m² or as per licencing at the point of prescription 3. Individuals with familial renal glycosuria 4. Documented or self-reported cirrhosis 5. Patients with hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 6. Individuals with recurrent balanitis, vaginal or urinary tract infections 7. Current or planned pregnancy, or breastfeeding 8. Females of childbearing age, unwilling to use adequate contraceptive methods during the study period 9. Currently on SLGT2i, GLP-1RA, basal-bolus or premixed insulin therapies 10. Contraindications to exercise or SGLT2i therapy 11. Current participation in another research study with investigational medical product 12. Scoring 0 on the SPPB, or otherwise unable to complete the test due to severe functional limitations 13. Active malignancy; at discretion of study clinician 14. Serious illness with life-expectancy < 1 year or other significant illness which, in the opinion of a study clinician, precludes involvement 15. Individuals with a history of chronic pancreatitis 16. Individuals with Latent Autoimmune Diabetes in Adults (LADA) 17. Patients with a history of excessive alcohol consumption 18. Patients on a severely calorie-restricted diet (i.e. <800 calories per day) 19. Patients with known heart failure Additional exclusion criteria for MRI scanning visits (this does not impact on the participant’s enrolment in the study): 20. Individuals with absolute contraindication to MRI that, in the opinion of a study clinician, precludes an MRI scan will not be invited to attend the MRI visits, but will engage in all other aspects of the study. Additional exclusion criteria for individuals wishing to undertake skeletal muscle biopsy sub-study (this does not impact on the participant’s enrolment in the main study): 21. Individuals taking any medication that, in the opinion of a study clinician, precludes involvement in the muscle biopsy sub-study (including blood thinning medications) 22. Individuals with any concurrent disease/condition that, in the opinion of a study clinician, precludes involvement in the muscle biopsy sub-study (including those with low platelet counts and those with blood-borne infections) 23. Individuals with a documented or self-reported history of local anaesthetic sensitivity Previous exclusion criteria: 1. Individuals with type 1, gestational or monogenic diabetes mellitus 2. eGFR <60 ml/min per 173m² or as per licencing at the point of prescription 3. Individuals with familial renal glycosuria 4. Documented or self-reported cirrhosis 5. Patients with hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 6. Individuals with recurrent balanitis, vaginal or urinary tract infections 7. Current or planned pregnancy, or breastfeeding 8. Females of childbearing age, unwilling to use adequate contraceptive methods during the study period 9. Currently on SLGT2i, GLP-1RA, basal-bolus or premixed insulin therapies 10. Contraindications to exercise or SGLT2i therapy 11. Current participation in another research study with an investigational medical product 12. Scoring 0 on the SPPB, or otherwise unable to complete the test due to severe functional limitations 13. Active malignancy; at discretion of study clinician 14. Serious illness with life-ex
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Physical function measured using the modified physical performance test (mPPT) at baseline, 12, and 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 04/08/2025: 1. HbA1c (mmol/l, %) at baseline, 12 and 24 weeks 2. Weight (kg) at baseline, 12, and 24 weeks 3. BMI (kg/m2) at baseline, 12, and 24 weeks 4. DXA assessed body composition - total fat mass (kg), fat mass percentage (%), lean mass (kg), lean mass percentage (%) at baseline, 12, and 24 weeks 5. MRI assessed absolute values for left ventricular end-diastolic volume (LVEDV) (mL), and LV mass (g) at baseline and 24 weeks. LV mass/LVEDV will be reported as a measure of concentricity 6. VO2 peak from maximal exercise test - absolute value (ml), relative to body weight (ml/kg) and relative to lean mass (ml/kg) at baseline, 12, and 24 weeks 7. Quadriceps strength (Nm at 60°[isokinetic], 90° [isometric and isokinetic]and 120º[isokinetic) - reported as absolute (Nm), relative to body weight (Nm/kg) and relative to lean mass (Nm/kg) values at baseline, 12, and 24 weeks. Bicep strength (repetitions) will also be reported. 8. Patient-reported outcomes (PROM)- WHO Disability Assessment Schedule 2.0 at baseline, 12, and 24 weeks 9. Short physical performance battery (SPPB) score at baseline, 12, and 24 weeks 10. Resting heart rate (beats/minute) at baseline, 12, and 24 weeks 11. Handgrip strength (kg) at baseline, 12, and 24 weeks 12. DXA-derived appendicular (arms and legs) lean mass (kg), bone mineral density (T-score), total bone mineral density (g/m2), total bone mass (kg) at baseline, 12, and 24 weeks 13. Waist circumference (cm) and neck circumference (cm) at baseline, 12, and 24 weeks 14. Muscle ultrasonography derived quadriceps muscle cross-sectional area (cm2), muscle and subcutaneous fat thickness (cm), fibre angle pennation and echo intensity at baseline, 12, and 24 weeks 15. Resting metabolic rate (kcal/day) at baseline, 12, and 24 weeks 16. MRI assessed LV ejection fraction (%) at baseline and 24 weeks 17. Echocardiogram assessed diastolic transmitral flow velocities, E/A ratio and early diastolic mitral annular ve | — |
Countries
England, United Kingdom
Contacts
Public ContactEmily James
Outcome results
None listed