GliflOzin in eLderly Diabetic patiENts: A praGmatic Intraclass Evaluation Trial

Center for Outcomes Research and Clinical Epidemiology, Italy1,167 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

1,167

Conditions

Diabetes Mellitus, Type 2

Interventions

Eligibility

Sex: ALLMin age: 70 YearsMax age: 90 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Up to 24 months

Secondary Outcomes

Secondary Objectives - HbA1c

Change in HbA1c level (as a continuous variable) - %

Time frame: Up to 24 months

Secondary Objectives - body weight

Change in body weight (as a continuous variable) - Kg

Time frame: Up to 24 months

Secondary Objectives - systolic blood pressure

Change in systolic blood pressure (as a continuous variable) - mmHG

Time frame: 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

Time frame: Up to 24 months

Secondary Objectives - urinary albumin excretion rate

Change in urinary albumin excretion rate (as a continuous variable) - mg/L

Time frame: Up to 24 months

Secondary Objectives - medications

Change concomitant medications and their daily dosages

Time frame: Up to 24 months

Secondary Objectives - treatment satisfaction

Change in treatment satisfaction quantified as Diabetes Treatment Satisfaction Questionnaire (DTSQ).

Time frame: Up to 24 months

Secondary Objectives - biomarkers

Plasma/serum biomarkers of bone metabolism and cardiac function (in a subset of patients) with physiological parameter

Time frame: Up to 24 months