Clinical trial NCT05440591: Effects of Dapagliflozin and Metformin on Vascular Function in Newly-Diagnosed Treatment-Naive Type 2 Diabetes
Official title: Effects of Dapagliflozin and Metformin on Vascular Function in Newly-Diagnosed Treatment-Naive Type 2 Diabetes- A Randomised Controlled Trial (DMVascular Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Diabetes
Lead sponsor: Tan Tock Seng Hospital
Sponsor class: OTHER
First posted: 2022-07-01
Enrollment: 150
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open Label Parallel Randomised Controlled Trial
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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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Primary outcomes:
measure: Endothelial Function measured as reactive hyperaemia index (RHI-EndoPAT)
timeFrame: 3 months after initiation
measure: Carotid Femoral Pulse Wave Velocity
timeFrame: 3 months after initiation
Secondary outcomes:
measure: Augmentation index
timeFrame: 3 months after initiation
measure: Central pulse pressure
timeFrame: 3 months after initiation
measure: Advanced glycation end products
timeFrame: 3 months after initiation
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
Study officials:
affiliation: Tan Tock Seng Hospital
name: Rinkoo Dalan
role: PRINCIPAL_INVESTIGATOR
References: