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 = 109) or placebo (n = 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 = 0.0007) and fasting and postmeal plasma glucose (19 mg/dL, P = 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 (-2.2% [8%]) (P = 0.4). The change in plaque volume in the exenatide group was associated with changes in HbA1c (r = 0.38, P = 0.0004), body weight, and overall plasma glucose (r = 0.29, P = 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.
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 = 109) or placebo (n = 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 = 0.0007) and fasting and postmeal plasma glucose (19 mg/dL, P = 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 (-2.2% [8%]) (P = 0.4). The change in plaque volume in the exenatide group was associated with changes in HbA1c (r = 0.38, P = 0.0004), body weight, and overall plasma glucose (r = 0.29, P = 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.
Authors: Hertzel C Gerstein; Helen M Colhoun; Gilles R Dagenais; Rafael Diaz; Mark Lakshmanan; Prem Pais; Jeffrey Probstfield; Jeffrey S Riesmeyer; Matthew C Riddle; Lars Rydén; Denis Xavier; Charles Messan Atisso; Leanne Dyal; Stephanie Hall; Purnima Rao-Melacini; Gloria Wong; Alvaro Avezum; Jan Basile; Namsik Chung; Ignacio Conget; William C Cushman; Edward Franek; Nicolae Hancu; Markolf Hanefeld; Shaun Holt; Petr Jansky; Matyas Keltai; Fernando Lanas; Lawrence A Leiter; Patricio Lopez-Jaramillo; Ernesto German Cardona Munoz; Valdis Pirags; Nana Pogosova; Peter J Raubenheimer; Jonathan E Shaw; Wayne H-H Sheu; Theodora Temelkova-Kurktschiev Journal: Lancet Date: 2019-06-09 Impact factor: 79.321
Authors: John A Dormandy; Bernard Charbonnel; David J A Eckland; Erland Erdmann; Massimo Massi-Benedetti; Ian K Moules; Allan M Skene; Meng H Tan; Pierre J Lefèbvre; Gordon D Murray; Eberhard Standl; Robert G Wilcox; Lars Wilhelmsen; John Betteridge; Kåre Birkeland; Alain Golay; Robert J Heine; László Korányi; Markku Laakso; Marián Mokán; Antanas Norkus; Valdis Pirags; Toomas Podar; André Scheen; Werner Scherbaum; Guntram Schernthaner; Ole Schmitz; Jan Skrha; Ulf Smith; Jan Taton Journal: Lancet Date: 2005-10-08 Impact factor: 79.321
Authors: Loïc Boussel; Sandeep Arora; Joseph Rapp; Brian Rutt; John Huston; Dennis Parker; Chun Yuan; Hisham Bassiouny; David Saloner Journal: Radiology Date: 2009-06-09 Impact factor: 11.105
Authors: Raymond Q Migrino; Mark Bowers; Leanne Harmann; Robert Prost; John F LaDisa Journal: J Cardiovasc Magn Reson Date: 2011-08-03 Impact factor: 5.364