The Effects of Dapagliflozin on HDL Particles Subtypes and Reverse Cholesterol Transport in Type 2 Diabetic Patients

• Status: Completed
• Trial end date: 2016-09-01
• Target enrollment: 0
• Participant gender: All

Summary

In Phase 2b/3 clinical trials, Dapagliflozin has been shown to raise HDL cholesterol levels by about 4 mg/dl (1 mmol/l), which is generally considered a clinically-meaningful change. As this HDL cholesterol increase is carried out with concomitant improvement in glucotoxicity and body weight reduction, it is possible that treatment with Dapagliflozin also improves HDL function. This is important because clinical, epidemiological and experimental studies indicate that HDL function may be more important than HDL cholesterol levels in determining the protective cardiovascular effects of HDL particles. In addition, knowing the effects of Dapagliflozin on HDL function can help interpreting the increase in HDL cholesterol levels observed in Dapagliflozin-treated patients. Finally, discovery of extra-glycemic effects of Dapagliflozin will shed new light on the potential benefits of therapy with Dapagliflozin and SGLT2i in general. So far, no study evaluated the effects of Dapagliflozin (or other SGLT2i) on HDL function.

The investigators hypothesize that Dapagliflozin, in addition to raising HDL cholesterol levels, also increases HDL functionality, measured as reverse cholesterol transport and anti-oxidant capacity, in patients with T2DM

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Padova
• Collaborator: Azienda Ospedaliera di Padova
• Treatments: Dapagliflozin

Criteria

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures

• Female and male subjects aged 18-75 years

• Type 2 diabetes on oral agents +/- insulin

• Diabetes duration >6 months

• HbA1c 7.0-10.0%

Exclusion Criteria:

• Acute illness or infection

• Recent (within 1 month) surgery, trauma, cardiovascular event

• Recent (within 3 months) variation of statin therapy/dose

• Therapy with HDL-modifying drugs, such as fibrates, omega-3 fatty acids, and niacin

• Alcoholism

• Very high baseline HDL levels (>90 mg/dL)

• Previous history of recurrent (≥2 episodes) urinary tract infections or genital infections (a single remote episode not to be considered an exclusion criterion)

• History of hypotension, episodes of volume depletion / dehydration.

• Chronic renal failure (eGFR<60 ml/min/1.73 mq)

• Chronic liver disease (SGOT or GPT >2-fold ULN, or cirrhosis)

• Elevated hematocrit (>50% for men or >45% for women)

• Heart failure, NYHA classes III-IV

• Hypersensitivity to Dapagliflozin or its excipients

• Treatment with pioglitazone or GLP-1 receptor agonists

• Women with childbearing potential