limo
Researcher
Posts: 82
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Post by limo on Jun 27, 2023 8:48:30 GMT -5
worth noting, whilst tolerability data from the trial may cause some investor concern given a ~25% discontinuation rate with survodutide, there is potential for this to be improved upon in Phase 3 trials and remind that other GLP-1 (Trizepatide) based therapies were associated with >20% discontinuation rates in Phase 2 trials before optimization of titration/dosing schedules in Phase 3. So its on the right path. just need them to differentiate themselves by sticking it on TS!
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Post by prcgorman2 on Jun 27, 2023 9:10:00 GMT -5
I have to wonder if a greatly-reduced dose of an analog on TS might provide the desired effect (loss of appetite) without the side effects. The effect really only needs to last an hour or two between meals.
Maybe use an 80/20 mix (or whatever) of non-analog to analog to get instant + short-ish lasting result?
2 to 4 TS GLP-1 puffs a day, might be just the ticket.
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Post by sayhey24 on Jun 29, 2023 6:34:59 GMT -5
I have to wonder if a greatly-reduced dose of an analog on TS might provide the desired effect (loss of appetite) without the side effects. The effect really only needs to last an hour or two between meals. Maybe use an 80/20 mix (or whatever) of non-analog to analog to get instant + short-ish lasting result? 2 to 4 TS GLP-1 puffs a day, might be just the ticket. If you take a puff before each meal do you need an analog? I think this is what Peter and Al were investigating with native glp1. |
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Post by prcgorman2 on Jun 29, 2023 8:24:17 GMT -5
I have to wonder if a greatly-reduced dose of an analog on TS might provide the desired effect (loss of appetite) without the side effects. The effect really only needs to last an hour or two between meals. Maybe use an 80/20 mix (or whatever) of non-analog to analog to get instant + short-ish lasting result? 2 to 4 TS GLP-1 puffs a day, might be just the ticket. If you take a puff before each meal do you need an analog? I think this is what Peter and Al were investigating with native glp1. Appetite/hunger control only needs to happen between meals and presumably an hour or two after or before a meal. It can go into and out of the blood nearly instantly if the appetite suppressant effect lasts longer. |
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Post by sportsrancho on Jun 30, 2023 6:10:47 GMT -5
Except that you don’t over eat because you’re hungry:-)
People over eat because they want that sedated feeling that consuming half a pizza gives them..some people use food, some people use alcohol, some people use drugs. If food/carbs ..is your drug of choice an appetite suppressant drug will not continue to work.
Every diet works at first if you follow it, but then the novelty wears off and you have to go back to dealing with your feelings …and that’s what people are trying to avoid doing.
Now a doctor that’s never had a weight problem ..that has no desire to indulge in anything other than a nightly cup of ice cream is never going to understand this. However, I’ve been in the weight business for 25 years and I have seen it firsthand.
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Post by sayhey24 on Jun 30, 2023 6:27:49 GMT -5
Except that you don’t over eat because you’re hungry:-) People over eat because they want that sedated feeling that consuming half a pizza gives them..some people use food, some people use alcohol, some people use drugs. If food/carbs ..is your drug of choice an appetite suppressant drug will not continue to work. Every diet works at first if you follow it, but then the novelty wears off and you have to go back to dealing with your feelings …and that’s what people are trying to avoid doing. Now a doctor that’s never had a weight problem ..that has no desire to indulge in anything other than a nightly cup of ice cream is never going to understand this. However, I’ve been in the weight business for 25 years and I have seen it firsthand. OK - what is the average time until the novelty wears off? Ozempic is still selling like hot cakes and there are still shortages. These people are clearly dropping pounds for some period of time. If TS GLP1 worked how much could be sold annually, assuming its a $50B market. If Peter was right and you don't get the nausea with TS this seems like a potential blockbuster to me even if you need a puff before each meal/snack/cup of ice cream. |
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Post by prcgorman2 on Jun 30, 2023 7:21:36 GMT -5
Except that you don’t over eat because you’re hungry:-) People over eat because they want that sedated feeling that consuming half a pizza gives them..some people use food, some people use alcohol, some people use drugs. If food/carbs ..is your drug of choice an appetite suppressant drug will not continue to work. Every diet works at first if you follow it, but then the novelty wears off and you have to go back to dealing with your feelings …and that’s what people are trying to avoid doing. Now a doctor that’s never had a weight problem ..that has no desire to indulge in anything other than a nightly cup of ice cream is never going to understand this. However, I’ve been in the weight business for 25 years and I have seen it firsthand. I agree with your comment about satiety but the point is the appetite suppressant lowers that level. The half-pizza becomes two pieces. The two things a TS GLP-1 can help with is lesser appetite at meal time, and elimination of the urge to snack. I’ve never worn a CGM but have always assumed that the change in blood sugar is what triggers the snacking, and the change isn’t unhealthy, its just that it triggers hunger. If that’s true, then a relatively short-lived appetite suppresant (at much lower doses) might be just the thing to manage a reduction in calorie intake but without the unpleasant side effects. |
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Post by sportsrancho on Jun 30, 2023 9:12:13 GMT -5
No…. It’s not about the urge to snack and it’s not about your appetite. It’s about eating carbs to heighten your mood level so you’re not depressed ..it’s not about hunger.
You see this with diet drugs, they’re a big fad at first but then everyone moves onto the next one because if you’re over eating to hide from your feelings, the results don’t last, what lasts is getting therapy and treating the problem where it initially started.
To be clear ..if it’s about hunger yes, but most of the time it isn’t about hunger.
And sure it could be a blockbuster, there’s commercials 24/7 ..everybody wants to get on the bandwagon. Geez even my landlord wants to get on it.🤣 I just think if they stay on it eventually they’ll go back to their old eating habits or they’ll get off it and gain the weight right back. If you don’t change your habits, even gastric bypass doesn’t work.
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Post by prcgorman2 on Jun 30, 2023 11:52:43 GMT -5
Agree, but most people are able to maintain a weight and not just bounce back and forth in a wide range. The hope would be that they could lose the weight to get to a healthier weight, and then maintain at that healthier weight. I largely agree with most of your other observations too.
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Post by agedhippie on Jul 1, 2023 5:08:08 GMT -5
Agree, but most people are able to maintain a weight and not just bounce back and forth in a wide range. The hope would be that they could lose the weight to get to a healthier weight, and then maintain at that healthier weight. I largely agree with most of your other observations too. The people who are taking GLP-1 for weight loss in almost all cases regain weight when they stop. There is a long debate as to how this gets funded because there isn't a lot of point in reducing peoples weight for a couple of years, taking them off GLP-1 and having them promptly regain the weight. The likelihood is that GLP-1 treatment has to be indefinite, in which case how can this be afforded given the number of patients and the cost of the drugs. |
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Post by agedhippie on Jul 1, 2023 5:15:49 GMT -5
... If TS GLP1 worked how much could be sold annually, assuming its a $50B market. If Peter was right and you don't get the nausea with TS this seems like a potential blockbuster to me even if you need a puff before each meal/snack/cup of ice cream. The problem remains; that test was done with GLP-1 and not GLP-1 analogs which is needed to overcome the clearance rate of GLP-1. Suppose you take a puff of GLP-1 before you eat that ice cream, what do you do three minutes later when the GLP-1 has worn off and you start to feel you can eat again? Do you take another puff, and then what do you do three minutes later when that has worn off? This is exactly why GLP-1 analogs were designed, you need an extended half-life to avoid having to continuously dose. |
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Post by agedhippie on Jul 1, 2023 8:15:34 GMT -5
As an aside the 1mg Ozempic pen's list price is $573 in the US, and the UK NHS pays $24 per pen (they are free to diabetics)
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Post by sayhey24 on Jul 2, 2023 7:06:31 GMT -5
... If TS GLP1 worked how much could be sold annually, assuming its a $50B market. If Peter was right and you don't get the nausea with TS this seems like a potential blockbuster to me even if you need a puff before each meal/snack/cup of ice cream. The problem remains; that test was done with GLP-1 and not GLP-1 analogs which is needed to overcome the clearance rate of GLP-1. Suppose you take a puff of GLP-1 before you eat that ice cream, what do you do three minutes later when the GLP-1 has worn off and you start to feel you can eat again? Do you take another puff, and then what do you do three minutes later when that has worn off? This is exactly why GLP-1 analogs were designed, you need an extended half-life to avoid having to continuously dose. Based on Peter Richardson's comments I don't think he agrees with you based on what he was seeing. With that said, I really don't care if its native glp1 or an analog. We know the current oral approach BP is taking has issues which TS may be able to over come All I care about is having a blockbuster drug. I am 100% fine with loading Victoza on TS as long as we can sell $B+. For whatever reason Peter thought native glp1 had a chance and I think its worth another look especially since current management was not aware of the work done 15 years ago. |
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Post by agedhippie on Jul 2, 2023 9:18:33 GMT -5
The problem remains; that test was done with GLP-1 and not GLP-1 analogs which is needed to overcome the clearance rate of GLP-1. Suppose you take a puff of GLP-1 before you eat that ice cream, what do you do three minutes later when the GLP-1 has worn off and you start to feel you can eat again? Do you take another puff, and then what do you do three minutes later when that has worn off? This is exactly why GLP-1 analogs were designed, you need an extended half-life to avoid having to continuously dose. Based on Peter Richardson's comments I don't think he agrees with you based on what he was seeing. ... Reread what he said. Richardson says absolutely nothing about how to overcome the rapid clearance. His speculation is purely whether it could work, "In addition, if we are able to demonstrate the same weight reduction or satiety effects seen with long-acting analogues of native GLP, MKC253 may have therapeutic potential in obesity." How to achieve those effects is not touched on at all so it's hard to say he disagrees with me. |
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Post by sayhey24 on Jul 3, 2023 8:44:05 GMT -5
Based on Peter Richardson's comments I don't think he agrees with you based on what he was seeing. ... Reread what he said. Richardson says absolutely nothing about how to overcome the rapid clearance. His speculation is purely whether it could work, "In addition, if we are able to demonstrate the same weight reduction or satiety effects seen with long-acting analogues of native GLP, MKC253 may have therapeutic potential in obesity." How to achieve those effects is not touched on at all so it's hard to say he disagrees with me. Key word - "MAY" He does not say "doesn't", "will not". or "may not". Why in a press release would he say "may"? Of course the expectation was to have follow on studies to prove out his and Al's thought that it "may" and prove out it does. IDK but with the delay with clofazimine because of the fire it seems like a good opportunity to see if MKC253 may have therapeutic potential in obesity. If it does I think we are sitting on a blockbuster. |
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