Effect of semaglutide on coronary atherosclerosis progression in patients with type II diabetes: rationale and design of the semaglutide treatment on coronary progression trial

Abstract

Background: Cardiovascular morbidity and mortality are a major burden in patients with type 2 diabetic mellitus. In a landmark study, semaglutide (an injectable glucagon like peptide-1 receptor agonist) has been shown to significantly reduce cardiovascular events, however, the mechanism of benefit is still unknown. The primary hypothesis of our current study is to assess the effect of semaglutide to reduce progression of noncalcified coronary atherosclerotic plaque volume as measured by serial coronary CTA as compared to placebo in persons with diabetes over 1 year. Methods: One hundred forty patients will be enrolled after signing informed consent and followed up for 12 months and with a phone call 30 days after medical discontinuation. All the participants will undergo coronary artery calcium scoring and coronary computed tomography angiography at our center at baseline and 12 months. Eligible participants will be randomly assigned to semaglutide 2 mg/1.5 ml (1.34 mg/ml) prefilled pen for subcutaneous (SC) injection or placebo 1.5 ml, pen-injector for SC injection in a 1:1 fashion as add-on to their standard of care. Results: As of July 2019, the study was approximately 30% enrolled with an estimated enrollment completion by first quarter of 2020 and end of study by first quarter 2021. Thirty patients were enrolled as of 23 July 2019. Preliminary data of demographics and clinical characteristics were summarized. Conclusion: Our current study will provide important imaging-derived data that may add relevance to the clinically derived outcomes from liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results and semaglutide and cardiovascular outcomes in patients with type 2 diabetic mellitus 6 trials.

GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects

“…As GLP-1Rs are expressed in multiple brain regions, and GLP-1RAs such as liraglutide and lixisenatide can penetrate the blood-brain barrier, liraglutide and exendin-4 can be vagus-dependent or independent in the suppression of the food intake ( 176 ). Semaglutide is considered to control energy intake and reduce body weight probably by activating at discrete sites in the hypothalamus to reduce food craving, or by delaying the gastric emptying to affect appetite ( 119 , 177 , 178 ). In addition, GLP-1RAs could adjust the levels of the satiety signal in the arcuate nucleus in the hypothalamus, thereby increasing satiety and reducing caloric intake ( 179 ).…”

Cardiovascular Safety and Benefits of Semaglutide in Patients With Type 2 Diabetes: Findings From SUSTAIN 6 and PIONEER 6

“…To provide further insight, the effect of subcutaneous semaglutide vs. placebo on coronary atherosclerosis progression is currently being measured by multidetector computed tomography angiography over 1 year in~140 patients with T2D and CVD or at least one CV risk factor in the Semaglutide Treatment On Coronary Progression (STOP; NCT03985384) trial (54,55). Secondary endpoints include quantitative changes in different coronary plaque types and m o r p h o l o g y .…”

Clinical Efficacy and Mechanisms of Actions of the Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and High Risk of Cardiovascular Diseases

“…В настоящее время продолжается РКИ по оценке эффективности применения семаглутида в виде подкожных инъекций 1 раз в неделю по сравнению с плацебо в течение 12 мес для оценки прогрессирования атеросклероза коронарных артерий у пациентов с СД 2-го типа (n=140) [35]. Оценивать прогрессированиe атеросклероза коронарных артерий будут с помощью компьютерной томографической ангиографии.…”