Glycemic Durability After Metformin Failure (AMAZING)

Effect of Glimepiride, Vildagliptin, Pioglitazone and Canagliflozin on Durability of Glycemic Control After Metformin Failure in Type 2 Diabetes

Type 2 diabetes is epidemic and its treatment has become more and more difficult. Consensus algorithms have been developed to help clinicians to select among the numerous medications and their combinations for achieving and maintaining a target glycated hemoglobin A1c (HbA1c) of <7%.

AMAZING, a pragmatic clinical trial, aims to compare commonly used oral diabetes medications, when combined with metformin, on glycemia-lowering effectiveness.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Glimepiride; Drug: Vildagliptin; Drug: Pioglitazone; Drug: Canagliflozin

Detailed Description

• Source data verification: paper or electronic medical records.
• Statistical analysis: All analyses will compare the randomly assigned treatment groups under the intention- to-treat principle

• Study Type: Interventional
• Enrollment (Anticipated): 450
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dario Giugliano, MD; Phone Number: 39 081 5665054; Email: dario.giugliano@unina2.it

Study Locations

• Italy
  • Naples, Italy, 80138
    • Active, not recruiting
    • Department of Geriatrics and Metabolic Diseases
  • Naples, Italy, 80138
    • Recruiting
    • Katherine Esposito
    • Contact: Maria Ida Maiorino, MD; Email: mariaida.maiorino@unina2.it
    • Sub-Investigator: Giuseppe Bellastella, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly-diagnosed, type 2 diabetic patients, failing to diet

Exclusion Criteria:

• Suspected type 1 diabetes or secondary diabetes resulting from specific causes
• Current or previous (within past 3 months) treatment with any investigational drug
• Any major cardiovascular event in previous year
• Plans for pregnancy during the course of the study for women of childbearing potential
• Serum creatinine level >1.3 mg/dL in women and >1.4 mg/dL in men
• History of cancer, other than nonmelanoma skin cancer, that required therapy in the 5 years before randomization
• Treatment with oral, loal, systemic glucocorticoids 14. Treatment with atypical antipsychotics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glimepiride; up to 4 mg/day	Drug: Glimepiride; Weekly adjustment based on self-monitoring of blood glucose level to a maximum of 4 mg daily
Experimental: Vildagliptin; 50 mg bid	Drug: Vildagliptin; Reduce to 50 mg if estimated glomerular filtration rate (eGFR) <45 mL/min
Experimental: Pioglitazone; up to 30 mg/day	Drug: Pioglitazone; Start with 15 mg/day and advance to 30 mg/day
Experimental: Canagliflozin; 300 mg/day	Drug: Canagliflozin; Start with 200 mg/day and advance to 300 mg/day on the basis of fasting glucose monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome is maintenance of metabolic control (glycemic durability), defined as time to primary failure with a HbA1c value >7% on maximally tolerated doses of the assigned drug.	Six years

Secondary Outcome Measures

Outcome Measure	Time Frame
Continuous glucose monitoring for 72 consecutive hours at least once each year of follow-up	6 years

Other Outcome Measures

Outcome Measure	Time Frame
Changes of low density lipoprotein cholesterol level from baseline each year of follow up	6 years
Changes of high density lipoprotein cholesterol level from baseline each year of follow up	six years
Changes of triglyceride level from baseline each year of follow up	6 years

Collaborators and Investigators

• Sponsor: University of Campania "Luigi Vanvitelli"
• Investigators: Principal Investigator: Dario Giugliano, MD PHD, University of Campania "Luigi Vanvitelli"

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): October 1, 2015
• Study Completion (Anticipated): January 1, 2017

Study Registration Dates

• First Submitted: April 26, 2014
• First Submitted That Met QC Criteria: May 15, 2014
• First Posted (Estimate): May 20, 2014

Study Record Updates

• Last Update Posted (Estimate): April 20, 2016
• Last Update Submitted That Met QC Criteria: April 19, 2016
• Last Verified: November 1, 2015

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; Anti-Arrhythmia Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Protease Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Pioglitazone; Glimepiride; Vildagliptin; Canagliflozin
• Other Study ID Numbers: DGM 7-2006