Effects of Dapagliflozin and Metformin on Vascular Function in Newly-Diagnosed Treatment-Naive Type 2 Diabetes (DMVascular)

Effects of Dapagliflozin and Metformin on Vascular Function in Newly-Diagnosed Treatment-Naive Type 2 Diabetes- A Randomised Controlled Trial (DMVascular Study)

Trial Design: This is a 12 week randomised controlled open label trial comparing the impact of Dapagliflozin, Metformin and combination therapy on vascular function in newly diagnosed T2DM patients.

Study Overview

• Status: Recruiting
• Conditions: Diabetes
• Intervention / Treatment: Drug: MetFORMIN 500 Mg Oral Tablet; Drug: Dapagliflozin; Drug: Dapagliflozin / metFORMIN Pill

Detailed Description

Trial Design: This is a 12 week randomised controlled open label trial comparing the impact of Dapagliflozin, Metformin and combination therapy on vascular function in newly diagnosed T2DM patients.

Trial Participants: Approximately 150 newly diagnosed T2DM patients with randomization 1:1:1 to Metformin XR 500mg twice daily, Dapagliflozin 10 mg daily or Metformin XR 500/Dapagliflozin 5 mg daily

Primary Aim : To evaluate the influence of intervention on vascular function.

Secondary Aims:

1. To evaluate the influence on other parameters of vascular function and beds.
2. To evaluate the haemodynamics involving blood pressure regulation.
3. To evaluate the effects of SGLT2i versus Metformin on endothelial interactions (vascular permeability) and leukocyte-endothelial interactions (leukocyte rolling, adherence), endothelial regenerative capacity and other endothelial related pathways.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Rinkoo Dalan, MBBS; Phone Number: 63571000; Email: rinkoo_dalan@ttsh.com.sg
• Study Contact Backup: Name: Siti Zaidah; Email: siti_zaidah_abu_bakar@ttsh.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 308433
    • Recruiting
    • Tan Tock Seng Hospital
    • Contact: Siti Zaidah; Email: siti_zaidah_abu_bakar@ttsh.com.sg
    • Principal Investigator: Rnkoo Dalan, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to give informed consent
2. Age 30-65 years
3. Newly diagnosed (within the past 1 - 2 years) to have T2DM and not started on diabetes medications, HbA1c 6.4% to 10% (both inclusive) and/or OGTT 0 min glucose ≥7.0mmol/L and/or 120 min glucose ≥11.8mmol/L OR Recently diagnosed to have T2DM and treated with Metformin for not more than 5 years, HbA1c ≤ 8%
4. No recent change in medications or new medications
5. eGFR>60mL/min/1.73m2
6. Patient is otherwise well with no acute systemic illness in the last 2 weeks.
7. Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the trial

Exclusion Criteria:

1. History of ketoacidosis or any other conditions causing acidosis e.g. Alcohol dependence
2. Has a history of urinary tract infections or is at risk for urinary tract infections (e.g prostatomegaly, vesicoureteric reflux, kidney stones)
3. Patients on corticosteroids or immunosuppressive agents
4. Patients known to have HIV infection and/or on anti-retroviral agents
5. Patients with typical clinical features suggestive of T1DM (young onset with no family history of diabetes or first presentation as DKA were excluded). The endocrinologist (PI or co-I) will look at the patient profile to confirm diagnosis of T2DM.
6. Has severe liver dysfunction
7. Considered inappropriate by investigators due to any other reason.
8. Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
9. Significant renal impairment.
10. Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
11. Participants who have participated in another research trial involving an investigational product in the past 12 weeks.

12. Participants who have a history of Peripheral Arterial Disease or peripheral vascular disease or complains of lower limb claudication pain.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metformin; Metformin XR 500 mg tablets - up-to twice daily orally.	Drug: MetFORMIN 500 Mg Oral Tablet; Metformin 500 mg tablets twice daily
Experimental: Dapagliflozin; Dapagliflozin 10 mg tablets - once daily	Drug: Dapagliflozin; Dapagliflozin 10mg tablets
Experimental: MetforminXR 500/Dapagliflozin 5mg; MetforminXR 500/Dapagliflozin 5mg , tablets- once daily	Drug: Dapagliflozin / metFORMIN Pill; Combination pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial Function measured as reactive hyperaemia index (RHI-EndoPAT)		3 months after initiation
Carotid Femoral Pulse Wave Velocity	Sphygmocor determined cf-PWV	3 months after initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Augmentation index	Augmentation index-sphygmocor derived and RHI-endoPAT derived	3 months after initiation
Central pulse pressure	CPP-Sphygmocor derived	3 months after initiation
Advanced glycation end products	AGE reader measurements	3 months after initiation

Collaborators and Investigators

• Sponsor: Tan Tock Seng Hospital
• Investigators: Principal Investigator: Rinkoo Dalan, Tan Tock Seng Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): May 10, 2023
• Study Completion (Anticipated): May 10, 2023

Study Registration Dates

• First Submitted: June 27, 2022
• First Submitted That Met QC Criteria: June 29, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Metformin
• Other Study ID Numbers: DMV001

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