keangkong
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This interesting article proposes dividing patients non-responsible to GLP-1 drugs into three different categories
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YoYoFat
GLP-1 Specialist
Can you explain this in lay person?
keangkong
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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.
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
GLP-1 Apprentice
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.
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.
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.
JoonyO
GLP-1 Enthusiast
Those who have secretory deficiencies which are due to impaired enteroendecrine cell dysfunction? That would seem to explain ( to me anyway ) why some complain of " pronounced GI symptoms at low doses"? I'm not one of 'em ( I'm at 6mg -5 days and have not had any of what I've heard others complain of...YET🤞 ) but they relate their having sulpher burps, diarrhea and other GI issues at extremely low doses making them question whether they should continue use as treatments for weight loss.
It also says that they're "excellent responders to exogenous incretin therapy". Were I one of these super or hyper responders ( whatever the hell label they're given ) I would think I'd be looking into incretin therapy. And like GLP-1s initial introduction it seems that the studies are around T2D.
It also says that they're "excellent responders to exogenous incretin therapy". Were I one of these super or hyper responders ( whatever the hell label they're given ) I would think I'd be looking into incretin therapy. And like GLP-1s initial introduction it seems that the studies are around T2D.
skeptick
GLP-1 Apprentice
impaired enteroendecrine cell dysfunction Bet you can't say that fast five timesThose who have secretory deficiencies which are due to impaired enteroendecrine cell dysfunction? That would seem to explain ( to me anyway ) why some complain of " pronounced GI symptoms at low doses"? I'm not one of 'em ( I'm at 6mg -5 days and have not had any of what I've heard others complain of...YET🤞 ) but they relate their having sulpher burps, diarrhea and other GI issues at extremely low doses making them question whether they should continue use as treatments for weight loss.
It also says that they're "excellent responders to exogenous incretin therapy". Were I one of these super or hyper responders ( whatever the hell label they're given ) I would think I'd be looking into incretin therapy. And like GLP-1s initial introduction it seems that the studies are around T2D.
JoonyO
GLP-1 Enthusiast
Awe hell.🙁 I tried. Didn't even make it through the FIRST time without stumbling! 🤣🤣🤣
keangkong
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I said "impaired enteroendocrine cell dysfunction" five times correctly (in my view). I said the phrase quite slowly. I also did not say it in front of people. I'm not going even try saying it fast five times; that would not work. That would be like me trying to jump twenty feet into the air; it's not going to happen. I can't even say IECD fast five times.
Very interesting! Thank you kindly for posting. So if I am reading this correctly @keangkong, it’s saying that the first type of non responder the - receptor level resistance group, should respond to Reta if they find Tirz hasn’t worked for them?
And so the causes of non response in this group come about because of faulty/damaged receptors interactions in the pancreas caused chronic hyperglycemia/ inflammation/ or epigenetic modifications affecting receptor gene transcription.
And so the causes of non response in this group come about because of faulty/damaged receptors interactions in the pancreas caused chronic hyperglycemia/ inflammation/ or epigenetic modifications affecting receptor gene transcription.
keangkong
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I (a non-medical, not sciency person) interpret the article as you interpreted it other than the authors had included tons of caveats that you omitted. I believe you were just trying to be more bottom-line. They thought GIPR agonists would help people in the first catergory, but wanted the issue studied. "These agents offer a mechanistically distinct route around β-cell receptor impairment and merit prospective, mechanistic type-stratified evaluation before any firm clinical positioning [Citation.]" While the authors described possible causes of someone being the first type of nonresponder, they listed only possible causes. "The first type is receptor-level resistance, characterized by the reduced expression or faulty functionality of the GIPR or GLP-1R at the target tissue level, particularly in β-cells of the pancreas. This mechanism is well-documented in T2DM and may result from chronic hyperglycemia, inflammation, or epigenetic modifications affecting receptor gene transcription (Rajan et al. 2015)." (Italics added.)
