A novel bullfrog-derived GLP-1 analogue (bGLP-10) outperformed semaglutide in reducing blood sugar and food intake in obese mice, and when combined with the amylin analog cagrilintide, achieved 38.4% weight loss — significantly more than the semaglutide-cagrilintide combination (23.0%).
38.4% weight lossThe bullfrog GLP-1 analogue bGLP-10 combined with amylin analog cagrilintide achieved 38.4% weight loss in obese mice — significantly more than the semaglutide-cagrilintide combination at 23.0%
What the researchers found
bGLP-10 showed superior albumin affinity and receptor potency. At 10 nmol/kg, bGLP-10 significantly outperformed semaglutide in blood sugar reduction and food intake suppression (p<0.001). Chronic combination results: bGLP-10 + cagrilintide = -38.4% weight loss (p<0.001) vs semaglutide + cagrilintide = -23.0% vs bGLP-10 alone = -16.1% vs semaglutide alone = -10.9% vs cagrilintide alone = -5.7%. Superior glucose control and liver lipid management vs semaglutide-cagrilintide (p<0.001).
Why it matters
The combination of GLP-1 and amylin analogues is the next frontier in obesity treatment (Novo Nordisk's CagriSema is in phase 3 trials). This study suggests that natural GLP-1 peptides from non-mammalian species may be even more effective than current drugs, and that the right GLP-1-amylin combination could achieve unprecedented weight loss levels.
The numbers in context
10 bGLP-1 analogues designed. bGLP-10 showed superior albumin affinity and receptor potency. Outperformed semaglutide in DIO mice.
How the study worked
In vitro receptor binding and activation assays. In vivo: diet-induced obesity (DIO) mice on high-fat diet. Acute studies for blood sugar and food intake. Chronic combination study with bGLP-10 and/or cagrilintide vs semaglutide and/or cagrilintide. Outcomes: body weight, blood glucose, liver lipids.
Who was studied
Diet-induced obesity mice
What this study cannot tell us
Mouse study only — DIO mice don't fully model human obesity. No pharmacokinetic data in larger animals or humans. No safety/tolerability assessment. The comparison to semaglutide may not reflect optimized dosing. bGLP-10 is a novel compound with no clinical development track record.
How to read the evidence
Rated preliminary: impressive preclinical results in DIO mice but no human data. The head-to-head comparison with semaglutide adds value but species translation is uncertain.
When this study was published
Published in 2024. Timely given ongoing CagriSema (semaglutide + cagrilintide) clinical trials.
The bigger picture
Nature's peptide diversity is an underexplored resource for drug development. Bullfrog GLP-1 differs from human GLP-1, and these differences may confer therapeutic advantages. The 38.4% weight loss achieved with the bGLP-10-cagrilintide combination approaches surgical levels, suggesting next-generation peptide combinations could match or exceed bariatric surgery outcomes.
Questions still open
- Would bGLP-10's superiority over semaglutide hold in humans, or is it species-specific?
- What makes bullfrog GLP-1 structurally superior — which modifications drive the enhanced activity?
- Could the 38.4% weight loss level achieved in mice translate to clinically meaningful superiority over CagriSema in humans?
Common questions
Could a frog-derived peptide really be better than Ozempic?
What is combination GLP-1 + amylin therapy?
Read the original research
Identification and utility exploration of a highly potent and long-acting bullfrog GLP-1 analogue in GLP-1 and amylin combination therapy.
Peptides, 177, 171203
Citation
Sun, Xiao; Yang, Dawei; Li, Yan; Shi, Jingjing; Zhang, Xiaolong; Yi, Tingzhuang. (2024). Identification and utility exploration of a highly potent and long-acting bullfrog GLP-1 analogue in GLP-1 and amylin combination therapy.. Peptides, 177, 171203. https://doi.org/10.1016/j.peptides.2024.171203