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The cardiovascular actions at these receptors are well studied, but less is known about their combination. The aim was to explore the acute haemodynamic effects of dual agonism at the GLP\u20101 and glucagon receptor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Healthy male participants attended randomized, saline\u2010controlled intravenous infusion studies using glucagon (low, 25\u2009ng\/kg\/min), glucagon (high, 50\u2009ng\/kg\/min), exenatide (loading dose 50\u2009ng\/min for 30\u2009min then 25\u2009ng\/min) and exenatide:glucagon co\u2010infusion for 120\u2009min in Part A (glucagon dose\u2010comparison study) and 60\u2009min in Part B (dual\u2010agonism study).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In Part A (n\u2009=\u20097, median age 21 years, interquartile range 21\u201032 years), glucagon (high) increased heart rate by 11 beats per minute\u2009(bpm) (95% confidence interval [CI] 4\u201017\u2009bpm,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.01). In Part B (n\u2009=\u200912, median age 24 years, interquartile range 22\u201026 years), exenatide increased heart rate by 4\u00a0bpm (95% CI 2\u20106\u00a0bpm,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.001). Glucagon (low) increased heart rate by 4\u00a0bpm (95% CI 1\u20107\u00a0bpm,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.001). Co\u2010infusion of glucagon (low) and exenatide increased heart rate by 7\u00a0bpm (95% CI 4\u20109\u00a0bpm,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.001) and the rate pressure product by 793\u2009mmHg*bpm (95% CI 460\u20101127\u2009mmHg*bpm,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.001). There were no differences in cardiac output, blood pressure or heart rate variability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In healthy males, exenatide and glucagon co\u2010infusion acutely increases the rate pressure product, an indirect measure of cardiac work. This increase is driven by an increase in heart rate, rather than any change in systolic blood pressure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70282","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T09:37:33Z","timestamp":1759225053000},"page":"579-588","source":"Crossref","is-referenced-by-count":2,"title":["An experimental medicine protocol for exploring the haemodynamic effects of dual agonism at the glucagon\u2010like peptide\u20101 and glucagon receptor in healthy subjects"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1659-7644","authenticated-orcid":false,"given":"James","family":"Goodman","sequence":"first","affiliation":[{"name":"Division of Experimental Medicine and Immunotherapeutics, Department of Medicine University of Cambridge  UK"},{"name":"Clinical Pharmacology Department Cambridge University Hospitals NHS Foundation Trust  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