Glycemic Durability After Metformin Failure

Study Overview
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Brief Summary
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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.

Detailed Description
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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

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

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Glimepiride
* Drug: Vildagliptin
* Drug: Pioglitazone
* Drug: Canagliflozin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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