GliflOzin in eLderly Diabetic patiENts: A praGmatic Intraclass Evaluation Trial

Study Overview
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Brief Summary
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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.

Official Title
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Intraclass Safety and Efficacy Comparison Among SGLT-2 Inhibitors in Elderly Patients With Type 2 Diabetes. A Pragmatic, Phase IV, Multicenter, Open-label, Randomised Controlled Trial.

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Canagliflozin
* Drug: Dapagliflozin
* Drug: Empagliflozin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 70 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: canagliflozin<br>100 mg (or 50/850 mg and 50/1000 mg of the fixed association with metformin) or 300 mg (or the 150/850 mg and the 150/1000 mg fixed association with metformin). | Drug: Canagliflozin<br>* Canagliflozin If the patient is already on metformin, the fixed combination Canagliflozin / Metformin can be used.<br>|
| Active Comparator: dapagliflozin<br>10 mg (or 5/850 mg and 5/1000 mg of the fixed association with metformin; or 10/5 mg of the fixed dapagliflozin / saxagliptin combination) | Drug: Dapagliflozin<br>* 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.<br>|
| Active Comparator: empagliflozin<br>10 mg (or 5/850 mg and 5/1000 mg of the fixed association with metformin; or 5/5 mg of the empagliflozin / linagliptin combination) or 25 mg (or the 12.5/850 mg and the 12.5/1000 mg fixed association with metformin; or the 12.5/5 mg empagliflozin / linagliptin combination). | Drug: Empagliflozin<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Objective | 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. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Objectives - HbA1c | Change in HbA1c level (as a continuous variable) - % | Up to 24 months | 
| Secondary Objectives - body weight | Change in body weight (as a continuous variable) - Kg | Up to 24 months | 
| Secondary Objectives - systolic blood pressure | Change in systolic blood pressure (as a continuous variable) - mmHG | Up to 24 months | 
| Secondary Objectives - e-GFR | 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 | Up to 24 months | 
| Secondary Objectives - urinary albumin excretion rate | Change in urinary albumin excretion rate (as a continuous variable) - mg/L | Up to 24 months | 
| Secondary Objectives - medications | Change concomitant medications and their daily dosages | Up to 24 months | 
| Secondary Objectives - treatment satisfaction | Change in treatment satisfaction quantified as Diabetes Treatment Satisfaction Questionnaire (DTSQ). | Up to 24 months | 
| Secondary Objectives - biomarkers | Plasma/serum biomarkers of bone metabolism and cardiac function (in a subset of patients) with physiological parameter | Up to 24 months |