Exenatide and glucagon co-infusion increases myocardial glucose uptake and improves markers of diastolic dysfunction in adults with type 2 diabetes

Type 2 diabetes (T2D) significantly increases the risk of heart failure, a major cause of hospitalisation and increased morbidity and mortality. Dual and multi-agonist synthetic peptides at the GLP-1 and glucagon receptor are in clinical development as potential new treatments for a range of chronic...

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Vydáno v:Scientific reports Ročník 15; číslo 1; s. 21404 - 14
Hlavní autoři: Goodman, James, Schain, Martin, Di Stefano, Giovanni, Lupson, Victoria, Horn, Tracy, Hill, Marion, Manavaki, Roie, Fryer, Timothy D., Bumanlag-Amis, Elaine, Jalaludeen, Navazh, Jermutus, Lutz, Johansson, Edvin, Heurling, Kerstin, Haraldsson, Henrik, Evans, Mark, Cheriyan, Joseph, Johansson, Lars, Ambery, Philip, Wilkinson, Ian B.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 01.07.2025
Nature Portfolio
Témata:
18F-FDG
631/154/436
631/154/436/108
631/154/436/2388
692/699/2743
692/699/2743/137
692/699/2743/393
692/699/75
692/699/75/230
Adult
Aged
Biomarkers - metabolism
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Diastole - drug effects
Dual-agonism
Exenatide - administration & dosage
Female
GLP-1
GLP-1/glucagon
Glucagon
Glucagon - administration & dosage
Glucose - metabolism
Humanities and Social Sciences
Humans
Hypoglycemic Agents - administration & dosage
Male
Middle Aged
multidisciplinary
Myocardial glucose uptake
Myocardium - metabolism
Science
Science (multidisciplinary)
Dual-agonism
GLP-1
PET MRI
Glucagon
GLP-1/glucagon
Myocardial glucose uptake
CMR
Cardiac MRI
F-FDG
18F-FDG
ISSN:2045-2322, 2045-2322
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Shrnutí:Type 2 diabetes (T2D) significantly increases the risk of heart failure, a major cause of hospitalisation and increased morbidity and mortality. Dual and multi-agonist synthetic peptides at the GLP-1 and glucagon receptor are in clinical development as potential new treatments for a range of chronic metabolic conditions including T2D. Here, we aimed to explore the effects of GLP-1 and glucagon dual receptor agonism on myocardial glucose uptake (MGU) and myocardial function in T2D. Eight adults with a mean age of 52 ± 12 years and body mass index 31 ± 4 kg/m 2 attended three randomised infusion visits using combinations of 0.9% saline, glucagon (12.5 ng/kg/min) and exenatide:glucagon co-infusion (exenatide loading dose 50 ng/min for 30 min then 25 ng/min). MGU and myocardial function were assessed using 18 F-FDG PET-MRI. MGU increased in n  = 7/8 (88%) participants from a median of 9.2 × 10 −3 µmol/g/min (IQR 0.33–19 × 10 −3 µmol/g/min) with saline, to 20 × 10 −3 µmol/g/min (5.4–98 × 10 −3 µmol/g/min) with exenatide:glucagon, n  = 8, z  = 2.24, r =  0.79, P  < 0.05. Exenatide:glucagon significantly increased the median left ventricular global peak diastolic circumferential strain rate from 0.619 1/s (0.580–0.716 1/s) to 0.686 1/s (0.644–0.737 1/s) n  = 8, z  = 2.37, r =  0.84, P  < 0.05. Left ventricular global longitudinal contraction (as a measure global longitudinal strain) numerically increased by 0.6%, from − 16.0% with saline (-14.0-[-16.7]%) to -16.6% with exenatide:glucagon (-14.1-[-17.6]%), n  = 8, z =-1.54, r=- 0.54, P  = 0.123. Further studies are required to explore whether GLP-1/glucagon dual receptor agonists have a role to play in reducing cardiovascular risk and attenuating heart failure related outcomes in patients with chronic metabolic conditions such as T2D.
Bibliografie:ObjectType-Article-1
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-025-04559-3