Göttingen minipigs accurately reproduced the cardiovascular effects of liraglutide, an MC4 receptor agonist, and urocortin-2 seen in humans, validating the minipig as a safety testing model for peptide drugs.
All 3 matched humansCardiovascular profiles of liraglutide, MC4 receptor agonist, and urocortin-2 in minipigs qualitatively reproduced human clinical observations
What the researchers found
In telemetry-implanted Göttingen minipigs (n=6-8 per study):
- Liraglutide (3 nmol/kg, Day 7): significant HR increase (P<0.01), no BP changes — matching human clinical observations
- MC4 receptor agonist LY2112688 (0.1-0.15 mg/kg, Day 4): significant increases in HR (P<0.05), MAP (P<0.01), SBP (P<0.01), and DBP (P<0.05) — matching the hypertensive effect that halted MC4RA clinical development
- Urocortin-2 infusion: significant HR increase (P<0.05) and SBP decrease (P<0.05) — matching known vasodilatory effects in humans
All three peptides qualitatively reproduced their known human cardiovascular profiles, though absolute magnitudes may differ between species.
Why it matters
Cardiovascular side effects are a leading cause of drug failure. The MC4 receptor agonist class, for example, was largely abandoned due to blood pressure increases discovered in clinical trials. Having a reliable animal model that catches these issues early could save years of development time and protect human trial participants.
How the study worked
Three consecutive crossover studies in female Göttingen minipigs with surgically implanted telemetry devices measured mean arterial, systolic, and diastolic blood pressure, heart rate, activity, and body temperature. Each of the three peptide compounds was tested against vehicle control in the same animals.
What this study cannot tell us
Small sample sizes (6-8 animals per study). Only female minipigs were used. While qualitative effects matched human data, the quantitative magnitudes may differ between species. The study tested only three compounds, all with known cardiovascular profiles. The model's predictive value for peptides with unknown cardiovascular effects remains to be demonstrated.
How to read the evidence
This is a preclinical pharmacological validation study using telemetry in minipigs. The crossover design is rigorous for an animal study, and the comparison to known human effects provides strong face validity for the model.
When this study was published
Published in 2025 in the Journal of Pharmacological and Toxicological Methods, this is a timely validation study given the explosion of peptide drug development.
The bigger picture
As more peptide drugs enter development for obesity, diabetes, and cardiovascular disease, reliable safety models become critical. This study validates the Göttingen minipig — whose cardiovascular system closely resembles humans — as a translational model specifically for peptide therapeutics, potentially improving the efficiency of the drug development pipeline.
Questions still open
- Could this minipig model have predicted the MC4 receptor agonist blood pressure issue before human trials?
- How does the minipig model compare to other preclinical models (dogs, non-human primates) for cardiovascular safety prediction of peptide drugs?
- Should regulatory guidelines recommend minipig cardiovascular safety testing for all new peptide therapeutics?
Common questions
Why does liraglutide increase heart rate?
What happened with MC4 receptor agonists for obesity?
Read the original research
Exploratory safety investigations in normal, freely moving Göttingen Minipigs using telemetry: Pharmacological validation.
Journal of pharmacological and toxicological methods, 136, 108395
Citation
Jacobsen, Julie; Christoffersen, Berit Ø. (2025). Exploratory safety investigations in normal, freely moving Göttingen Minipigs using telemetry: Pharmacological validation.. Journal of pharmacological and toxicological methods, 136, 108395. https://doi.org/10.1016/j.vascn.2025.108395