This interesting article proposes dividing patients non-responsible to GLP-1 drugs into three different categories

[keangkong]

Fajkić, et al. (2025). Decoding incretin resistance - a mechanistic framework to reclassify therapeutic variability for GLP-1 receptor agonist therapy. Amino Acids 57, 55.

 

[YoYoFat]

Can you explain this in lay person?

 

[keangkong]

Can you explain this in lay person?

Not very well. Only that there are different people don't respond to GLP-1 drugs. And figuring out which reason applies may one day help turn those nonresponders into people who benefit from GLP-1 drugs.

 

[Jfrick11]

Can you explain this in lay person?

The article essentially says......when someone doesn’t respond well to GLP-1 receptor agonist therapy, it’s not just because “the drug failed” — it might be because their biology isn’t suited (for now) to that therapy, due to receptor issues, signalling issues, or lack of endogenous hormone release. They argue that this could make it important in recognizing which mechanism is at play can help choose a more appropriate therapy, rather than simply increasing dose or changing drug without any insight. Having said that...they also say that currently there is no simple, validated diagnostics in every day practice to say definitively which “type” a person is.

 

[lostlakebear]

This is very interesting. Thank you for posting. My response to tirz has been somewhat muted compared to many on this forum. I fit the receptor-level resistance profile. I can live with slow and steady. I feel stuck unless I look back siz months at a time.

 

[eyfm!]

I didn’t respond to Tirzepatide at all for nearly 9 months and only lost about 6 pounds. I was on the highest dose and dealt with awful side effects like bloating, nausea, sulfur burps, fatigue, and just feeling miserable overall.

About 2.5 months ago, I switched to Retatrutide plus Cagrilintide, and I’m already down 33 pounds. Once I added cagri, the food noise basically disappeared. I think we need much more research on non-responders, because I definitely don’t fit into any of the categories described here.