Targeting the Ghrelin System: Multiple Strategies to Treat Obesity and Metabolic Disease | Research

The takeaway

Review of ghrelin-GHSR targeted strategies for obesity treatment including ghrelin antibodies, RNA spiegelmers, GHSR antagonists/inverse agonists, and GOAT inhibitors — multiple approaches to suppress the hunger hormone system.

5+ blocking strategies
Multiple approaches to suppress ghrelin hunger signaling are in development, each with unique advantages for obesity treatment

What the researchers found

Ghrelin-GHSR targeting strategies include ghrelin-neutralizing antibodies/spiegelmers, GHSR antagonists/inverse agonists, GOAT enzyme inhibitors, and approaches to decrease ghrelin synthesis. Animal efficacy demonstrated for multiple compounds.

Why it matters

Ghrelin is the only known circulating appetite-stimulating hormone. Blocking it complements GLP-1 drugs (which enhance satiety), potentially enabling combination therapy for greater weight loss.

The numbers in context

Ghrelin: 28 amino acids; secreted by gastric X/A cells; endogenous GHSR ligand

How the study worked

Narrative review of therapeutic strategies targeting the ghrelin-GHSR pathway for obesity and metabolic diseases.

Who was studied

N/A (review of animal and in vitro studies)

What this study cannot tell us

Mostly preclinical compounds. No ghrelin-targeting drugs approved for obesity. Safety of chronic hunger hormone suppression unclear.

How to read the evidence

Not applicable (narrative review). Based on preclinical data.

When this study was published

Published 2021. Ghrelin-targeting continues alongside GLP-1 drugs.

The bigger picture

Ghrelin blockade and GLP-1 activation are complementary anti-obesity mechanisms. Combining both could achieve weight loss approaching surgical levels.

Questions still open

Would combining ghrelin blockade with GLP-1 agonists produce superior weight loss?
Which approach is closest to clinical approval?
Are there safety concerns with chronic ghrelin suppression?

Common questions

Why not just block ghrelin to stop hunger?

Multiple approaches are being developed, but ghrelin also protects against low blood sugar and has other functions. The right balance of suppression needs to be found.

How would this compare to Ozempic?

GLP-1 drugs enhance satiety. Ghrelin blockers reduce hunger. Combining both could theoretically produce greater appetite control than either alone.

Read the original research

Ghrelin Based Therapy of Metabolic Diseases.

Current medicinal chemistry, 28(13), 2565-2576

View on PubMed ↗Publisher’s paper ↗

Citation

Liang, Yuan; Yin, Wenzhen; Yin, Yue; Zhang, Weizhen. (2021). Ghrelin Based Therapy of Metabolic Diseases.. Current medicinal chemistry, 28(13), 2565-2576. https://doi.org/10.2174/0929867327666200615152804