NCT02608905

Effect of Dapagliflozin on Inflammation and Endothelial Function

The Effect of Dapagliflozin on Inflammation and Endothelial Function

• Status: Terminated
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 21 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors reduce hyperglycemia and improve peripheral insulin sensitivity by ameliorating glucotoxicity. Insulin resistance in type 2 diabetes (T2DM) is associated with endothelial dysfunction and vascular inflammation. Thus strategies to improve insulin sensitivity and lower glucotoxicity may improve endothelial inflammation and vascular inflammation. However, the effects of these agents on vascular inflammation and endothelial function is not known in patients with type 2 diabetes although anti-inflammatory properties have been demonstrated in various animal models. In the present study the investigators will assess if dapagliflozin treatment for 12 weeks decreases monocyte inflammation and improves endothelial function in patients with type 2 diabetes on metformin monotherapy.

Detailed description

The insulin-resistant state of type 2 diabetes mellitus (T2DM) is largely mediated by inflammatory pathways affecting skeletal muscle which is the primary site of whole body insulin resistance. Nuclear factor kappa B (NFkappaB) regulates pro-inflammatory cytokines which ultimately impair skeletal muscle insulin signaling and fatty acid oxidation; its activity reflects overall inflammatory tone in skeletal muscle. Recent human studies confirm that NFkappaB is elevated in the skeletal muscle of T2DM human subjects. Furthermore, the same inflammatory processes and signaling impairments contribute to worsening endothelial dysfunction, which is an independent predictor for future cardiovascular events in T2DM. In addition, these SGLT-2 Inhibitors reduce body weight, visceral adiposity, systolic and diastolic blood pressure, microalbuminuria, and oxidative stress. However, there are no studies examining the effects of SGLT-2 inhibitor therapy on NFkappaB and other inflammatory mediators in humans with T2DM. Moreover, no studies have examined the effect of SGLT-2 inhibitor therapy on endothelial function in this population. In the present study the investigators will assess whether dapagliflozin treatment for 12 weeks reduces monocyte inflammation and improves endothelial dysfunction in patients with type 2 diabetes on metformin monotherapy.

Conditions

• Type 2 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	Dapagliflozin	Patients with Type 2 diabetes will be randomized to receive dapagliflozin 5 mg daily for 2 weeks followed by10 mg daily for 10 weeks by mouth or matching placebo for 12 weeks. All subjects will receive measurements of fasting plasma glucose, Free Fatty Acids, inflammatory markers and adipocytokines, monocyte inflammation, as well as ultrasound assessment of flow-mediated dilatation (FMD) of the brachial artery at baseline and after 12 weeks of drug treatment with either dapagliflozin or placebo.
DRUG	Placebo	Patients with Type 2 diabetes will be randomized to receive dapagliflozin 5 mg daily for 2 weeks followed by10 mg daily for 10 weeks by mouth or matching placebo for 12 weeks. All subjects will receive measurements of fasting plasma glucose, Free Fatty Acids, inflammatory markers and adipocytokines, monocyte inflammation, as well as ultrasound assessment of flow-mediated dilatation (FMD) of the brachial artery at baseline and after 12 weeks of drug treatment with either dapagliflozin or placebo.

Timeline

• Start date: 2015-11-01
• Primary completion: 2019-03-01
• Completion: 2019-03-01
• First posted: 2015-11-20
• Last updated: 2020-04-08
• Results posted: 2020-04-08

Locations

1 site across 1 country: United States