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

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.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Metformin

Detailed Description

This study is a randomised, double blinded clinical trial and will be undertaken in primary care and community sites across Australia and tertiary care centres in Sri Lanka. 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.

• Study Type: Interventional
• Enrollment (Estimated): 994
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sarah Stanton; Email: sstanton@georgeinstitute.org.au
• Study Contact Backup: Name: Emma Zhang; Phone Number: +61 2 8052 4337; Email: ezhang1@georgeinstitute.org.au

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2042
      • Recruiting
      • The George Institute for Global Health
      • Principal Investigator: Bruce Neal
      • Principal Investigator: Clare Arnott
      • Contact: Sarah Stanton; Email: sstanton@georgeinstitute.org.au
      • Contact: Emma Zhang; Phone Number: +61 2 8052 4337; Email: ezhang1@georgeinstitute.org.au
  • Queensland
    • Brisbane, Queensland, Australia, 4000
      • Recruiting
      • The George Institute for Global Health
      • Principal Investigator: Bruce Neal
      • Principal Investigator: Clare Arnott
      • Contact: Sarah Stanton; Email: sstanton@georgeinstitute.org.au
      • Contact: Emma Zhang; Phone Number: +61 2 8052 4337; Email: ezhang1@georgeinstitute.org.au
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Monash University
      • Contact: Simone Spark; Email: simone.spark@monash.edu
      • Contact: Zachary Flanagan; Email: Zachary.Flanagan@monash.edu
      • Principal Investigator: Sophia Zoungas
• Sri Lanka
  • Colombo, Sri Lanka, 00700
    • Not yet recruiting
    • National Hospital of Sri Lanka 2
    • Contact: Uditha Bulugahapitiya; Phone Number: +94 777 440 208; Email: udithakaush@gmail.com
    • Principal Investigator: Uditha Bulugahapitiya
  • Colombo 10, Sri Lanka, 00700
    • Recruiting
    • National Hospital of Sri Lanka 1
    • Contact: Manilka Sumanatilleke; Phone Number: +94 777 440 208; Email: manilkasumana@gmail.com
    • Principal Investigator: Manilka Sumanatilleke
  • Jaffna, Sri Lanka, 40000
    • Recruiting
    • Jaffna Teaching Hospital
    • Contact: Mahalingam Ararinthan; Phone Number: 0772619589; Email: ara.jho@gmail.com
    • Principal Investigator: Mahalingam Aravinthan
  • Kandy, Sri Lanka, 20000
    • Recruiting
    • Kandy National Hospital
    • Contact: Charles Antonypillai; Phone Number: +94773417639; Email: cantonypillai@gmail.com
    • Principal Investigator: Charles Antonypillai
  • Southern Province
    • Galle, Southern Province, Sri Lanka, 80000
      • Not yet recruiting
      • National Hospital - Galle
      • Contact: Muditha Weerakkody; Phone Number: +94 714 050 524; Email: mudithaweerakkody@gmail.com
      • Principal Investigator: Muditha Weerakkody

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 ≥45 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
Anxiety and depression symptoms measured by HADS	Effects of dapagliflozin vs. metformin, from baseline to 24 months, on anxiety and depression symptoms measured by the Hospital Anxiety and Depression Scale (HADS)	24 months

Collaborators and Investigators

• Sponsor: The George Institute
• Collaborators: Monash University; University of Sydney; The University of New South Wales
• Investigators: Study Chair: Bruce Neal, The George Institute for Global Health (Sydney, Australia); Study Chair: Clare Arnott, The George Institute for Global Health (Sydney, Australia)

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 19, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (Actual): April 25, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes; Metformin; Renal decline; Sodium Glucose Co-Transporter 2 inhibitor
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Metformin; Dapagliflozin
• Other Study ID Numbers: P01148

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

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