Ertugliflozin Versus Hydrochlorothiazide in Reducing Sympathetic Neural Overactivity in Patients With Hypertension and Recently-diagnosed Type 2 Diabetes.

• Status: Withdrawn
• Trial end date: 2020-08-31

Summary

The sodium-glucose cotransporter 2 (SGLT2) inhibitors are an exciting new class of antidiabetic drugs that cause a modest reduction in high blood pressure and large reductions in the risk of cardiovascular disease (CVD) outcomes and renal outcomes in patients with advanced type 2 diabetes and very high CVD risk. However, the mechanistic underpinning of these CVD benefits is not well understood. Mechanistic studies are needed to define specific biologic targets and thus optimize therapeutic benefits.

Type 2 diabetes mellitus is firmly established as a state of sympathetic neural overactivity, which may contribute to coexistent hypertension, heart failure, sudden cardiac death, macro- and micro-vascular complications of diabetes, and diabetic nephropathy. In patients recently diagnosed with Type 2 diabetes, microelectrode recordings of sympathetic nerve activity (SNA) targeted to the skeletal muscle circulation have shown both:

1. abnormally high resting (ambient) levels of sympathetic nerve activity; and

2. greatly exaggerated increases in sympathetic nerve activity during isometric (static) handgrip exercise.

The purpose of the proposed study is to determine if Ertugliflozin, a SGLT2 inhibitor, constitutes an effective countermeasure against sympathetic overactivity in patients with diagnosed hypertension and recently diagnosed type 2 diabetes by normalizing the high resting level of muscle sympathetic nerve activity (SNA) as measured by intraneural microelectrodes in the peroneal nerve.

Thus, an effective countermeasure is an urgent unmet medical need. The SGLT2 inhibitors hold exciting promise to address this need.

• Phase: Phase 4

Details

• Lead Sponsor: Cedars-Sinai Medical Center
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: 5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-1-hydroxymethyl-6,8-dioxabicyclo(3.2.1)octane-2,3,4-triol; Antihypertensive Agents; Ertugliflozin; Hydrochlorothiazide; Sodium-Glucose Transporter 2 Inhibitors