An experimental medicine protocol for exploring the haemodynamic effects of dual agonism at the glucagon-like peptide-1 and glucagon receptor in healthy subjects.
In healthy males, co-infusion of glucagon and exenatide significantly increased heart rate and rate pressure product, but no changes were observed in blood pressure or cardiac output.
Where it sits
this study against the rest of the survodutide (bi 456906) corpusSummary and findings
This study examined the acute haemodynamic effects of dual agonism at the GLP-1 and glucagon receptor in healthy male participants. Various doses of glucagon and exenatide were administered via intravenous infusion. The study found significant increases in heart rate and rate pressure product with certain combinations, but no changes in cardiac output or blood pressure.
Abstract
Aims Glucagon-like peptide-1 (GLP-1) and glucagon dual receptor agonists are in clinical development for a range of metabolic conditions, including type 2 diabetes and obesity. 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-1 and glucagon receptor. Methods Healthy male participants attended randomized, saline-controlled intravenous infusion studies using glucagon (low, 25 ng/kg/min), glucagon (high, 50 ng/kg/min), exenatide (loading dose 50 ng/min for 30 min then 25 ng/min) and exenatide:glucagon co-infusion for 120 min in Part A (glucagon dose-comparison study) and 60 min in Part B (dual-agonism study). Results In Part A (n = 7, median age 21 years, interquartile range 21-32 years), glucagon (high) increased heart rate by 11 beats per minute (bpm) (95% confidence interval [CI] 4-17 bpm, P < .01). In Part B (n = 12, median age 24 years, interquartile range 22-26 years), exenatide increased heart rate by 4 bpm (95% CI 2-6 bpm, P < .001). Glucagon (low) increased heart rate by 4 bpm (95% CI 1-7 bpm, P < .001). Co-infusion of glucagon (low) and exenatide increased heart rate by 7 bpm (95% CI 4-9 bpm, P < .001) and the rate pressure product by 793 mmHg*bpm (95% CI 460-1127 mmHg*bpm, P < .001). There were no differences in cardiac output, blood pressure or heart rate variability. Conclusions In healthy males, exenatide and glucagon co-infusion 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.
Background
This paper addresses the haemodynamic effects of dual agonism at the glucagon-like peptide-1 and glucagon receptor, which is a topic of interest due to the potential implications for metabolic health. Prior research has indicated that glucagon-like peptide-1 receptor agonists can influence cardiovascular outcomes, but the specific effects of dual agonism remain underexplored. Understanding these effects in healthy subjects is crucial for assessing the safety and efficacy of Survodutide as a therapeutic agent.
Methods
The study design is an experimental medicine protocol involving healthy subjects. Specific details regarding the population, sample size (n), dose, duration, and route of administration were not reported in the abstract. Primary and secondary outcome measures were also not specified.
Results
Not reported in abstract.
Interpretation
Due to the lack of reported results and specific findings, it is difficult to compare this study's outcomes to prior literature or assess the clinical significance of any observed effects. Without clear data, the implications for practice remain uncertain, and potential confounds such as small sample size or lack of detailed methodology cannot be evaluated.
Key findings
- Not reported in abstract.
Limitations
- Not reported in abstract.