GliflOzin in eLderly Diabetic patiENts: A praGmatic Intraclass Evaluation Trial (GOLDEN-AGE)

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.

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 Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Canagliflozin; Drug: Dapagliflozin; Drug: Empagliflozin

• Study Type: Interventional
• Enrollment (Anticipated): 1167
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years to 90 years (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: canagliflozin; 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; Canagliflozin If the patient is already on metformin, the fixed combination Canagliflozin / Metformin can be used.
ACTIVE_COMPARATOR: dapagliflozin; 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; 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.
ACTIVE_COMPARATOR: empagliflozin; 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; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Objectives	Hospitalization for any cause	Up to 24 months
Safety Objectives	Hospitalization for heart failure and/or cardiovascular causes	Up to 24 months
Safety Objectives	All-cause death and Cardiovascular death	Up to 24 months
Safety Objectives	Severe hypoglycemia	Up to 24 months
Safety Objectives	Genitourinary tract infections	Up to 24 months
Safety Objectives	Dehydration / hypovolemia events	Up to 24 months
Safety Objectives	Bone fractures	Up to 24 months
Safety Objectives	Leg/foot amputations	Up to 24 months
Safety Objectives	Diabetic ketoacidosis	Up to 24 months

Collaborators and Investigators

• Sponsor: Center for Outcomes Research and Clinical Epidemiology, Italy
• Collaborators: Italian Society of Diabetology

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 30, 2021
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: March 1, 2021
• First Submitted That Met QC Criteria: March 10, 2021
• First Posted (ACTUAL): March 12, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Empagliflozin; Canagliflozin
• Other Study ID Numbers: TRS-2019-00002051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No