Frailty and the preceding 'pre-frail' state in patients with type 2 Diabetes Mellitus. MedDRA version: 21.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Forxiga
Product Name: Forxiga
Product Code: Not applicable
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Dapagliflozin
CAS Number: 461432-26-8
Other descriptive name: Forxiga
Co
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (i) Men and women (ii) Age 40 to 75 years, inclusive (iii) 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; see below) (iv) HbA1c 6.5 to 10% (47 to 86 mmol/mol), inclusive (v) Historical evidence of functional limitation or frailty defined as at least one of : a. Impaired physical function or frailty; SPPB score 1 to 10 (inclusive) recorded within the preceding 5 years b. A coding of mild-to-moderate frailty based on the Electronic Frailty Index (eFI) within primary care c. V02peak = 18 ml/kg recorded within the preceding 5 years d. SARC-F questionnaire score of 4 or more (vi) BMI = 25 kg/m2 (= 22.5 kg/m2 if of Ssouth Asian ethnicity) (vii) Weight stable; =65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: (i) Individuals with type 1, gestational or monogenic diabetes mellitus (ii) eGFR < 60 ml.min-1 per 1.73m2 or as per licencing at the point of prescription (iii) Individuals with familial renal glycosuria (iv) Documented or self-reported cirrhosis (v) Patients with hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption (vi) Individual with recurrent balanitis, vaginal or urinary tract infections (vii) Current or planned pregnancy, or breast feeding (viii) Females of childbearing age, unwilling to use adequate contraceptive methods during the study period (ix) Currently on SLGT2i, GLP-1RA, basal-bolus or premixed insulin therapies (x) Contra-indications to exercise or SGLT2i therapy (xi) Current participation in another research study with investigational medical product (xii) Scoring 0 on the SPPB, or otherwise unable to complete the test due to severe functional limitations (xiii) Active malignancy; at discretion of study clinician (xiv) Serious illness with life-expectancy < 1 year or other significant illness which, in the opinion of a study clinician, precludes involvement (xv) Individuals with history of chronic pancreatitis (xvi) Individuals with Latent Autoimmune Diabetes in Adults (LADA) (xvii) Patients with a history of excessive alcohol consumption (xviii) Patients on a severely calorie restricted diet (i.e. <800 calories per day) Additional exclusion criteria for MRI scanning visits (this does not impact on the participant’s enrolment in the study) (i) Individuals with absolute contra-indication 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) (i) Individuals taking any medication that, in the opinion of a study clinician, preclude involvement in the muscle biopsy sub-study (including blood thinning medications). (ii) 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). (iii) Individuals with a documented or self-reported history of local anaesthetic sensitivity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this study is to investigate the effects of exercise training in individuals prescribed dapagliflozin for the management of type 2 diabetes on physical function, compared to diet-induced weight loss or dapagliflozin alone. ;Secondary Objective: Major secondary objectives are to examine the effects of dapagliflozin-plus-exercise or dapagliflozin alone on markers of cardiac function, factors underpinning physical function and other markers of cardiometabolic health.;Primary end point(s): The primary endpoint is the difference in the change in physical function between groups (measured using the modified physical performance test; mPPT) at 24 weeks. All other comparisons and outcomes will be considered secondary. ;Timepoint(s) of evaluation of this end point: The change in physical function between groups will be measured at 24 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Difference between groups at 24 weeks in relative aerobic capacity, lean body mass and circumferential peak early-diastolic strain rate (all powered), other indices of physical activity/fitness and body composition, other indices of cardiac structure and function, HbA1c, cardiovascular risk factors, systemic inflammation, skeletal muscle metabolic signalling pathways (protein balance, insulin signalling, inflammatory), mental wellbeing and quality of life (all exploratory). ;Timepoint(s) of evaluation of this end point: The difference between groups will be measured at 24 weeks, as per the primary end point. The time-course of change will also be assessed at 12 weeks. | — |
Countries
United Kingdom
Contacts
Public ContactProfessor Melanie Davies
University of Leicester
Outcome results
None listed