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<p>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&#xa0;kg/m<sup>2</sup> 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&#xa0;min then 25 ng/min). MGU and myocardial function were assessed using <sup>18</sup>F-FDG PET-MRI. MGU increased in <i>n</i> = 7/8 (88%) participants from a median of 9.2 × 10<sup>−3</sup> µmol/g/min (IQR 0.33–19 × 10<sup>−3</sup> µmol/g/min) with saline, to 20 × 10<sup>−3</sup> µmol/g/min (5.4–98 × 10<sup>−3</sup> µmol/g/min) with exenatide:glucagon, <i>n</i> = 8, <i>z</i> = 2.24, <i>r =</i> 0.79, <i>P</i> &lt; 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) <i>n</i> = 8, <i>z</i> = 2.37, <i>r =</i> 0.84, <i>P</i> &lt; 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]%), <i>n</i> = 8, <i>z</i>=-1.54, <i>r=-</i>0.54, <i>P</i> = 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • James Goodman,
  • Martin Schain,
  • Giovanni Di Stefano,
  • Victoria Lupson,
  • Tracy Horn,
  • Marion Hill,
  • Roie Manavaki,
  • Timothy D. Fryer,
  • Elaine Bumanlag-Amis,
  • Navazh Jalaludeen,
  • Lutz Jermutus,
  • Edvin Johansson,
  • Kerstin Heurling,
  • Henrik Haraldsson,
  • Mark Evans,
  • Joseph Cheriyan,
  • Lars Johansson,
  • Philip Ambery,
  • Ian B. Wilkinson

摘要

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/m2 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 18F-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.