Diabetes Mellitus, Type 2
Conditions
Brief summary
Three SGLT2i were commercially available in Italy at the time the trial was designed: canagliflozin, dapagliflozin, and empagliflozin. Preliminary evidence suggests that the higher dose canagliflozin (300 mg/day) might exert a stronger glucose-lowering effect than dapagliflozin or empagliflozin. The clinical relevance of this putative difference is however unknown. On the other side, the use of canagliflozin, but not empagliflozin and dapagliflozin, has been associated with an increased risk of some adverse events, namely bone fractures and lower limb amputations. Currently, the available information on the efficacy and safety of SGLT2i in elderly (70+ years) patients with type 2 diabetes are is very scant. Thus, a compelling need now exists of comparing efficacy and safety of the commercially available SGLT2i in a population of frail patients at high risk of cardiovascular and renal diseases.
Interventions
DRUGCanagliflozin
Canagliflozin If the patient is already on metformin, the fixed combination Canagliflozin / Metformin can be used.
DRUGDapagliflozin
Dapagliflozin If the patient is already on metformin, the fixed combination dapagliflozin / metformin can be used. If the patient is already on a DPP-4 inhibitor, the fixed dose combination dapagliflozin / saxagliptin can be used.
DRUGEmpagliflozin
If the patient is already on metformin, the fixed combination empagliflozin / metformin can be used. If the patient is already on a DPP-4 inhibitor, the fixed dose combination empagliflozin / linagliptin can be used.
Sponsors
Italian Society of Diabetology
Center for Outcomes Research and Clinical Epidemiology, Italy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
70 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes * Age 70+ years * Male or female * Prevalent cardiovascular disease (symptomatic or asymptomatic) or eGFR \<90 ml/min/1.73 m2 and above the lower limit for initiation of SGLT2i according to label (currently eGFR \<60 ml/min/1.73 m2) * HbA1c above individualized target * Indication to add SGLT2i
Exclusion criteria
* Age \>90 years * Estimated life expectancy \<1 year * Very high risk of genitourinary tract infections (\>2 events in the last 6 months) * Recent weight loss (\>5% in \<6 months) * Inability to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Objective | Up to 24 months | The primary objective is to compare the proportion of patients treated with each SGLT2i drug, who achieve the individualized HbA1c target without level-2 hypoglycaemia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Objectives - HbA1c | Up to 24 months | Change in HbA1c level (as a continuous variable) - % |
| Secondary Objectives - body weight | Up to 24 months | Change in body weight (as a continuous variable) - Kg |
| Secondary Objectives - systolic blood pressure | Up to 24 months | Change in systolic blood pressure (as a continuous variable) - mmHG |
| Secondary Objectives - e-GFR | Up to 24 months | Change in e-GFR (as a continuous variable). The slope of eGFR decline will be calculated over time in the three treated groups - mL/min |
| Secondary Objectives - medications | Up to 24 months | Change concomitant medications and their daily dosages |
| Secondary Objectives - treatment satisfaction | Up to 24 months | Change in treatment satisfaction quantified as Diabetes Treatment Satisfaction Questionnaire (DTSQ). |
| Secondary Objectives - biomarkers | Up to 24 months | Plasma/serum biomarkers of bone metabolism and cardiac function (in a subset of patients) with physiological parameter |
| Secondary Objectives - urinary albumin excretion rate | Up to 24 months | Change in urinary albumin excretion rate (as a continuous variable) - mg/L |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety Objectives | Up to 24 months | Hospitalization for any cause |
Outcome results
None listed