Great question. The honest answer is: we're still figuring this out.

GIP receptors are expressed in the brain, including in the hypothalamus, and there's evidence that GIP signaling contributes to appetite regulation and may enhance the effects of GLP-1 receptor activation.¹ Some researchers believe the dual agonism of tirzepatide explains its superior weight loss compared to semaglutide — it's hitting two complementary pathways.

However, the GIP receptor's role in the reward system is less well-characterized than GLP-1's. Most of the reward/food noise research has focused on GLP-1 specifically. It's an active area of investigation.

Anecdotally, many people on this forum report equal or greater food noise reduction on tirzepatide vs. semaglutide, which could support a GIP contribution. But anecdotes are not data, and we need more controlled studies.

The emerging triple agonists (GLP-1/GIP/glucagon, like retatrutide) will add another layer of complexity. Exciting times in this field.

¹ Zhang et al., "GIP has neuroprotective effects in Alzheimer and Parkinson's disease models," Peptides, 2021.

I started the first thread in this forum about food noise disappearing. Coming full circle to read the neuroscience behind it is deeply validating.

The part about willpower being "holding back a river with your hands" — I felt that in my soul. That's what I did for 20 years. And I thought the river was my fault. It was never my fault. The river was just too strong.

amsterdam_pete the medication has calmed the river. And I can finally put my hands down.

Thank you, NeuroNate. This post should be pinned to the top of the entire forum.

Pinned. This is now our reference post for the neuroscience of GLP-1 and food noise. Thank you, NeuroNate, for making complex science accessible and compassionate.

For anyone new here: if you're struggling with food noise, cravings, or the psychological burden of obesity, you are not morally failing. Your neurobiology is working against you, and there are now medications that can help. Talk to your doctor. And come back here for the community support.

This forum exists because nobody should have to fight the river alone.

It's 2am. I've been lurking on this forum for months. I've never posted. But I just read this entire thread and I'm lying in bed crying because for the first time in my life, I understand why I am the way I am.

I'm calling my doctor tomorrow. Thank you all.

Call them. We'll be here when you get back.