Dapagliflozin, Cardio-Metabolic Risk Factors and Type-2 Diabetes

• Status: Unknown status
• Trial end date: 2019-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Dapagliflozin is a member of the sodium-glucose cotransporter-2 (SGLT2) inhibitor class antidiabetes agents which produces significant and sustained reductions in glycemic parameters in patients with type 2 diabetes (T2DM). However, its non-glycemic effects are still largely unknown.

The investigators will evaluate for the first time the effect of dapagliflozin on multiple cardio-metabolic risk markers in one study. So far, no data on the effects of dapagliflozin as well as other SGLT-2 inhibitors on subclinical atherosclerosis, endothelial function, inflammatory markers, cytokines and atherogenic lipoproteins is available.

In addition, the investigators will examine microRNAs (miRNAs) implicated in the development and progression of atherosclerotic disease. Again, no data is currently available on dapaglifozin's as well as other SGLT-2 inhibitors' effects on miRNAs.

The results of this study will show for the first time the potential multiple, non-glycemic effects of dapagliflozin, reducing multiple cardio-metabolic risk markers, which will ultimately lead to decreased CV risk.

In addition, specific mechanisms of the dapagliflozin cardiovascular action will be investigated.

Finally, the results of this study may pave the way for personalized therapy (using the results on miRNAs).

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

Details

• Lead Sponsor: University of Palermo
• Collaborators: AstraZeneca; University of Catania
• Treatments: Dapagliflozin; Metformin

Criteria

Inclusion Criteria:

• men and women with T2DM;

• age >18;

• BMI ≥20 kg/m^2;

• HbA1c 7.0-9.0 %;

• receiving metformin therapy at least 1500 mg/day for at least 8 weeks before screening;

• plasma triglycerides <400 mg/dL, plasma LDL-cholesterol < 250 mg/dL;

• stabile daily dose(s) of hypolipidemic drugs (statins, ezetimibe) for at least 7 weeks prior to the day of randomization;

• adequately controlled blood pressure (≤140/90 mmHg) to be maintained during the study according to Standard of Care;

• able to swallow whole tablets.

Exclusion Criteria:

• pregnancy or willingness to became pregnant;

• severe liver dysfunction (alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 3 times upper limit of normal);

• renal failure with glomerular filtration rate (eGFR) <60 ml/min/1.73m^2;

• major cardiovascular event (myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischaemic attack) within 12 weeks before screening;

• severe infections (such as HIV and HCV);

• any malignancy within 5 years before screening.