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First Human Trial Protocol for Measuring Cardiovascular Effects of GLP-1/Glucagon Dual Agonists

evidence
The takeaway

This experimental medicine protocol provides the first systematic framework for evaluating the acute hemodynamic effects of GLP-1/glucagon dual receptor agonists in humans, addressing cardiovascular safety questions.

First systematic protocol

No previous framework existed for evaluating the acute cardiovascular effects of GLP-1/glucagon dual agonists in humans

What the researchers found

An experimental medicine protocol for systematically evaluating acute hemodynamic effects of GLP-1/glucagon dual agonists, addressing cardiovascular safety concerns about glucagon receptor agonism.

Why it matters

Glucagon increases heart rate and energy expenditure, but the cardiovascular safety of chronic glucagon receptor activation is unknown. This protocol addresses a critical knowledge gap.

How the study worked

Experimental medicine study protocol for healthy volunteers, measuring acute cardiovascular parameters (HR, BP, cardiac output, SVR) after GLP-1/glucagon dual agonist administration.

What this study cannot tell us

Protocol description; no results yet. Acute effects may not predict chronic cardiovascular outcomes. Healthy volunteers may respond differently than obese/diabetic patients.

How to read the evidence

Study protocol without results. Establishes methodology for a critical safety question.

When this study was published

Published in 2025.

The bigger picture

As dual and triple agonists move toward approval, understanding their cardiovascular effects is essential for safe clinical deployment.

Questions still open

  • Will acute hemodynamic effects predict chronic cardiovascular safety?
  • How do effects compare between different dual agonist molecules?
  • Should cardiac monitoring be standard for patients starting dual agonists?

Common questions

Why study the heart effects of dual agonists?
Glucagon increases heart rate and has cardiovascular effects. When combined with GLP-1 in dual agonist drugs, understanding these effects is crucial for patient safety.
Are dual agonist drugs safe for the heart?
We don't know yet — that's exactly what this study protocol aims to determine. Early cardiovascular safety data is essential before these drugs are widely prescribed.

Read the original research

An experimental medicine protocol for exploring the haemodynamic effects of dual agonism at the glucagon-like peptide-1 and glucagon receptor in healthy subjects.

British journal of clinical pharmacology, 92(2), 579-588

Citation

Goodman, James; Parker, Victoria E; McEniery, Carmel M; Di Stefano, Giovanni; Hubsch, Annette; Vamvaka, Evangelia; Helmy, Jo; Kaloyirou, Fotini; Jalaludeen, Navazh; Barker, Peter; Jermutus, Lutz; Cheriyan, Joseph; Ambery, Philip; Wilkinson, Ian B. (2026). An experimental medicine protocol for exploring the haemodynamic effects of dual agonism at the glucagon-like peptide-1 and glucagon receptor in healthy subjects.. British journal of clinical pharmacology, 92(2), 579-588. https://doi.org/10.1002/bcp.70282