Targeting Impaired NO-sGC-cGMP Signaling With Vericiguat Improves Coronary Endothelial Function in Patients With Metabolic Syndrome or Type 2 Diabetes
Year: 2026
Type: conference-paper
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Patients with diabetes or the metabolic syndrome are at increased risk for coronary artery disease, in part due to impaired endothelial nitric oxide (NO) bioavailability and reduced downstream soluble guanylate cyclase (sGC)-cGMP signaling. Coronary endothelial function (CEF) can be assessed noninvasively by MRI as the percent change in coronary artery cross-sectional area (CSA) during isometric handgrip exercise (IHE), an endothelial NO–dependent stress. We hypothesized that pharmacologic enhancement of sGC signaling with vericiguat would improve CEF in patients with cardiometabolic disease and coronary endothelial dysfunction. We conducted a randomized, double-blind, placebo-controlled study in 32 patients with diabetes or the metabolic syndrome and impaired baseline CEF, randomized 2:1 to vericiguat or placebo. CEF was assessed by MRI at baseline and after six weeks of study drug administration following titration to 10 mg/day or maximally tolerated dose. Mean age was 60.6±8.6 years and 40.6% were women. There were no baseline group differences in clinical characteristics or CEF. In the placebo group, CSA during IHE did not significantly change from baseline to follow-up (-7.4±8.5% to +1.4±12.6%; p = 0.0512). In contrast, the vericiguat group demonstrated significant improvement in CSA during IHE from -6.8±6.7% to +3.1±8.5% (p=0.0002). Achieved vericiguat dose was independently associated with improvement in CEF (β=6.34; p=0.0497). There were no significant group differences in adverse events. Vericiguat improved MRI-assessed coronary endothelial function in patients with cardiometabolic disease, providing in vivo human evidence that enhancement of NO-sGC-cGMP signaling improves coronary vascular function.
Institution: Johns Hopkins University
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Funder: Merck
OpenAlex ID: W7163143628