SGLT2 Inhibitors As First Line Therapy to Prevent Renal Decline in Type 2 Diabetes

Study Overview
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Brief Summary
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The aim of the trial is to evaluate the effects of the SGLT2 inhibitor, dapagliflozin, compared to metformin on annual decline in eGFR when used as first line therapy in people with Type 2 Diabetes.

Detailed Description
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This study is a randomised, double blinded, community-based clinical trial and will be undertaken in primary care sites across Victoria, New South Wales and Queensland, Australia. Following a 4-week active run-in period, eligible participants will be randomised to either dapagliflozin 10mg daily, or metformin XR 2000mg daily in a 1:1 ratio.

Official Title
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SGLT2 Inhibitors As First Line Therapy to Prevent Renal Decline in Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of T2D; Aged ≥18 years; Body mass index > 18.5 kg/m2; Drug naïve, or managed with metformin monotherapy and willing to be randomised to either dapagliflozin or metformin; eGFR ≥30 ml/min/1,73m2; and Signed informed consent. Exclusion Criteria: Have an immediate need for rapid intensification of glucose lowering therapy due to marked hyperglycaemia; or There is a definite indication for, or contraindication to, either metformin or SGLT2 inhibitor; or They have clearly documented coronary artery disease (defined as a previous acute coronary syndrome, coronary stent or bypass surgery) or clearly documented heart failure (defined on the basis of a hospital admission, specialist diagnosis or an echocardiogram or other imaging modality); or Pregnant or breast-feeding.

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin 10mg<br>1x over-encapsulated Dapagliflozin 10mg tablet and 2x Metformin placebo tablets, taken orally once daily for 2 years | Drug: Dapagliflozin<br>* SGLT2 inhibitor<br>|
| Active Comparator: Metformin XR 2000mg<br>2x Metformin XR 1000mg tablets and 1x over-encapsulated Dapagliflozin placebo, taken orally once daily for 2 years | Drug: Metformin<br>* Metformin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of decline in eGFR | Change in estimated glomerular filtration rate (eGFR) from study baseline to 24 months, in ml/min/1.73m2/year | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine albumin creatinine ratio | Effects of dapagliflozin vs metformin, from baseline to 24 months, on urine albumin creatinine ratio (mg/g) | 24 months | 
| Serum creatinine | Effects of dapagliflozin vs metformin, from baseline to 24 months, on serum creatinine (umol/L) | 24 months | 
| HbA1C | Effects of dapagliflozin vs metformin, from baseline to 24 months, on HbA1C (%) | 24 months | 
| Fasting blood glucose | Effects of dapagliflozin vs metformin, from baseline to 24 months, on fasting blood glucose (mmol/L) | 24 months | 
| Systolic and diastolic blood pressure | Effects of dapagliflozin vs metformin, from baseline to 24 months, on systolic and diastolic blood pressure (mmHg) | 24 months | 
| Body weight | Effects of dapagliflozin vs metformin, from baseline to 24 months, on body weight (kg) | 24 months | 
| Quality of life measured by EQ-5D-5L | Effects of dapagliflozin vs metformin, from baseline to 24 months, on quality of life measured by European Quality of Life 5-Dimensional Assessment, 5-Level version | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Renal decline, Metformin, Sodium Glucose Co-Transporter 2 inhibitor