TY - JOUR
T1 - The Effect of Exenatide Once Weekly on Carotid Atherosclerosis in Individuals With Type 2 Diabetes
T2 - An 18-Month Randomized Placebo-Controlled Study
AU - Koska, Juraj
AU - Migrino, Raymond Q.
AU - Chan, Keith C.
AU - Cooper-Cox, Kelly
AU - Reaven, Peter D.
N1 - Funding Information:
Acknowledgments.The authorsacknowledge the excellent project assistance provided by Michell Sorley, Linda McDonald, Seth Truran, Douglas Boyd, Frances Keltner, Florentina Lipan, James Carlyle, and staff of the Phoenix Veterans Affairs Radiology and Nutrition Departments. Duality of Interest. This study was supported by an investigator-initiated grant from AstraZeneca (toP.D.R.).Nootherpotentialconflictsofinterest relevant to this article were reported.
Publisher Copyright:
© 2021, American Diabetes Association Inc.. All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - OBJECTIVE Glucagon-like peptide 1 receptor agonists (GLP-1RAs) improved multiple proatherogenic risk factors and reduced cardiovascular events in recent clinical trials, suggesting that they may slow progression of atherosclerosis. We tested whether exenatide once weekly reduces carotid plaque progression in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS In a double-blind, pragmatic trial, 163 participants were randomized (2:1) to exenatide (n 5 109) or placebo (n 5 54). Changes in carotid plaque volume and composition were measured at 9 and 18 months by multicontrast 3 Tesla MRI. Fasting and post–high-fat meal plasma glucose and lipids, and endothelial function responses, were measured at 3, 9, and 18 months. RESULTS Exenatide reduced hemoglobin A1c (HbA1c) (estimated difference vs. placebo 0.55%, P 5 0.0007) and fasting and postmeal plasma glucose (19 mg/dL, P 5 0.0002, and 25 mg/dL, P < 0.0001, respectively). Mean (SD) change in plaque volume in the exenatide group (0.3% [2%]) was not different from that in the placebo group (22.2% [8%]) (P 5 0.4). The change in plaque volume in the exenatide group was associated with changes in HbA1c (r 5 0.38, P 5 0.0004), body weight, and overall plasma glucose (r 5 0.29, P 5 0.007 both). There were no differences in changes in plaque composition, body weight, blood pressure, fasting and postmeal plasma triglycerides, and endothelial function between the groups. CONCLUSIONS Exenatide once weekly for up to 18 months improved fasting and postprandial glycemic control but did not modify change in carotid plaque volume or composition. This study raises the possibility that short-term antiatherosclerotic effects may not play a central role in the cardiovascular benefits of GLP-1RAs.
AB - OBJECTIVE Glucagon-like peptide 1 receptor agonists (GLP-1RAs) improved multiple proatherogenic risk factors and reduced cardiovascular events in recent clinical trials, suggesting that they may slow progression of atherosclerosis. We tested whether exenatide once weekly reduces carotid plaque progression in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS In a double-blind, pragmatic trial, 163 participants were randomized (2:1) to exenatide (n 5 109) or placebo (n 5 54). Changes in carotid plaque volume and composition were measured at 9 and 18 months by multicontrast 3 Tesla MRI. Fasting and post–high-fat meal plasma glucose and lipids, and endothelial function responses, were measured at 3, 9, and 18 months. RESULTS Exenatide reduced hemoglobin A1c (HbA1c) (estimated difference vs. placebo 0.55%, P 5 0.0007) and fasting and postmeal plasma glucose (19 mg/dL, P 5 0.0002, and 25 mg/dL, P < 0.0001, respectively). Mean (SD) change in plaque volume in the exenatide group (0.3% [2%]) was not different from that in the placebo group (22.2% [8%]) (P 5 0.4). The change in plaque volume in the exenatide group was associated with changes in HbA1c (r 5 0.38, P 5 0.0004), body weight, and overall plasma glucose (r 5 0.29, P 5 0.007 both). There were no differences in changes in plaque composition, body weight, blood pressure, fasting and postmeal plasma triglycerides, and endothelial function between the groups. CONCLUSIONS Exenatide once weekly for up to 18 months improved fasting and postprandial glycemic control but did not modify change in carotid plaque volume or composition. This study raises the possibility that short-term antiatherosclerotic effects may not play a central role in the cardiovascular benefits of GLP-1RAs.
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U2 - 10.2337/DC20-2014
DO - 10.2337/DC20-2014
M3 - Article
C2 - 33495294
AN - SCOPUS:85107981230
VL - 44
SP - 1385
EP - 1392
JO - Diabetes Care
JF - Diabetes Care
SN - 1935-5548
IS - 6
ER -