'The Downsized' shares fresh Survodutide updates.

diplomat

diplomat

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From what I can see, Survo's dropout numbers are awful, so it probably won't rank among the Greats.

Once the trial data came out, Zealand Pharma stock fell roughly 25%.

For investors, tolerability ranks as 1 of the most critical factors for market success, and since the (trial) discontinuation rate is roughly 2 to 4 times even Wegovy, Survo looks like a dud.

After reviewing early data, I'm not giving up on Survodutide that quickly - I have a few kits, and I'm hoping its visceral and liver fat emphasis might assist with my Humpty Dumpty shaped body!
 
My guess is that without GIP, it's a tough one to take. (sorry for the pun)

One thing stood out to me: results from the Phase III SYNCHRONIZE-1 trials show that at the top dose studied (6.0 mg), survodutide produces a 63.1% drop in liver fat and a 34.0% drop in visceral fat across 76 weeks.
 
Just A Cat said:

My guess is that without GIP, it's a tough one to take. (sorry for the pun)

One thing stood out to me: results from the Phase III SYNCHRONIZE-1 trials show that at the top dose studied (6.0 mg), survodutide produces a 63.1% drop in liver fat and a 34.0% drop in visceral fat across 76 weeks.
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Any idea how that stacks up against the reta trials?
 
Chiming in with "I'll do anything for you..." 🙂

When it comes to liver fat, S achieved a 63.1% decrease by week 76, while R reached an 86.0% decrease by week 48.

For visceral fat, S showed a 34.0% drop at week 76, compared with R's 48.0% drop at week 48.
 
Just A Cat said:

Chiming in with "I'll do anything for you..." 🙂

When it comes to liver fat, S achieved a 63.1% decrease by week 76, while R reached an 86.0% decrease by week 48.

For visceral fat, S showed a 34.0% drop at week 76, compared with R's 48.0% drop at week 48.
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I have to mention that reta, in some way, brought me from s2 fatty liver all the way to normal, 3% fat.... I had spent roughly 15 months on tirz, ret and both.
 
For me, it's tough to see what a GLP drug gains by leaving out GIP agonism. GIP agonism works against the side effects that come from GLP-1, which means either fewer side effects or a higher maximum tolerated dose, and that makes the drug work better. There will be people who barely get side effects at all, so for them it may not matter much. But when you look at the average, the GIP in reta should make it better both for weight loss and for cutting liver fat, while causing fewer side effects, compared with a glucagon/GLP-1 agonist.
 
Airborne Daddy said:

Just A Cat said:

Chiming in with "I'll do anything for you..." 🙂

When it comes to liver fat, S achieved a 63.1% decrease by week 76, while R reached an 86.0% decrease by week 48.

For visceral fat, S showed a 34.0% drop at week 76, compared with R's 48.0% drop at week 48.
Click to expand...
I have to mention that reta, in some way, brought me from s2 fatty liver all the way to normal, 3% fat.... I had spent roughly 15 months on tirz, ret and both.
Click to expand...
Nice work. That's something to be proud of.



Now, let's go over 3 categories of fat. SubQ fat, which is mostly just a nuisance. Visceral Fat, which is mainly a health risk. Liver Fat, which is above all hazardous.
 
The titration protocol in those trials was extremely rigid. Participants had no choice but to keep increasing their dose, which sets it apart from the Lilly studies — there, people could either move up or stay put at the same dose for a longer stretch, and on the reta trials even skipping doses was allowed.

On top of that, a sizable number of subjects in the survo placebo group were quietly using a glp. The placebo arm still ended up with 5% weight loss. For the next round of trials, the study design needs to be better. And to any researchers here who are backing survo: go low and slow. Titrate slowly.
 
Getting stuck with placebo is a raw deal. If I signed up expecting complimentary fat reduction and wound up on the losing end, I would be furious.
 
Someone I know took part in the trial and lost 60lbs over a 12 month period. She had diabetes too, which was the reason she joined the study. Once it ended, they simply ceased providing her with survo, yet she was able to maintain the weight loss and keep diabetes at bay. That is the account she gave me.
 
ColdSmoke said:

Getting stuck with placebo is a raw deal. If I signed up expecting complimentary fat reduction and wound up on the losing end, I would be furious.
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Exactly! I've always been curious — what goes into a placebo? Is it saline solution, or something else?
 
Kaydz said:

ColdSmoke said:

Getting stuck with placebo is a raw deal. If I signed up expecting complimentary fat reduction and wound up on the losing end, I would be furious.
Click to expand...

Exactly! I've always been curious — what goes into a placebo? Is it saline solution, or something else?
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BAC from the vendor
 
Just adding my own take here — reta gave me skin-related issues I couldn't handle, so I switched over to survo. For roughly 12 months, stacking it with tirz, I saw solid results and zero side effects. Nothing to grumble about, though I realize it's not the most budget-friendly pick next to reta.
 
lessthanhalf said:

For me, it's tough to see what a GLP drug gains by leaving out GIP agonism. GIP agonism works against the side effects that come from GLP-1, which means either fewer side effects or a higher maximum tolerated dose, and that makes the drug work better. There will be people who barely get side effects at all, so for them it may not matter much. But when you look at the average, the GIP in reta should make it better both for weight loss and for cutting liver fat, while causing fewer side effects, compared with a glucagon/GLP-1 agonist.
Click to expand...
There is also a fairly intriguing study that could shift how you view that position:


https://www.mdpi.com/2075-4418/16/13/1979
 
ColdSmoke said:

Getting stuck with placebo is a raw deal. If I signed up expecting complimentary fat reduction and wound up on the losing end, I would be furious.
Click to expand...
Participants in the placebo arms believed the same thing, which is why they were covertly using a glp. This brings up the issue of whether placebo controlled trials involving glp’s can still be conducted going forward. Most likely, they will be made to conduct them against a comparator drug (semaglutide).
 
Kaydz said:

ColdSmoke said:

Getting stuck with placebo is a raw deal. If I signed up expecting complimentary fat reduction and wound up on the losing end, I would be furious.
Click to expand...

Exactly! I've always been curious — what goes into a placebo? Is it saline solution, or something else?
Click to expand...

When it comes to injections, it's usually normal saline.
 
tubby said:

lessthanhalf said:

For me, it's tough to see what a GLP drug gains by leaving out GIP agonism. GIP agonism works against the side effects that come from GLP-1, which means either fewer side effects or a higher maximum tolerated dose, and that makes the drug work better. There will be people who barely get side effects at all, so for them it may not matter much. But when you look at the average, the GIP in reta should make it better both for weight loss and for cutting liver fat, while causing fewer side effects, compared with a glucagon/GLP-1 agonist.
Click to expand...
There is also a fairly intriguing study that could shift how you view that position:


https://www.mdpi.com/2075-4418/16/13/1979
Click to expand...
That caught my eye too, and there is certainly something intriguing there. As far as I'm aware, though, nobody outside of research settings is checking GLP-1 or GIP blood levels. Still, it appears to suggest that responses to a given drug can differ based on someone's starting glp or gip levels, even though the reason behind that is a bit tough for me to grasp. The body's natural amounts of these hormones are tiny next to what GLP-1 medications do, so it surprises me somewhat that baseline readings would carry any weight at all. Without first testing levels, is there any practical use? Perhaps it makes sense for people who don't do well on their first glp drug to experiment with another, and maybe even to give semaglutide a shot when tirzepatide isn't working well, though that thought stings a little considering how awful my own experience with it was. Even so, I'd still say tirz or reta is the better place to begin.
 
lessthanhalf said:

tubby said:

lessthanhalf said:

For me, it's tough to see what a GLP drug gains by leaving out GIP agonism. GIP agonism works against the side effects that come from GLP-1, which means either fewer side effects or a higher maximum tolerated dose, and that makes the drug work better. There will be people who barely get side effects at all, so for them it may not matter much. But when you look at the average, the GIP in reta should make it better both for weight loss and for cutting liver fat, while causing fewer side effects, compared with a glucagon/GLP-1 agonist.
Click to expand...
There is also a fairly intriguing study that could shift how you view that position:


https://www.mdpi.com/2075-4418/16/13/1979
Click to expand...
That caught my eye too, and there is certainly something intriguing there. As far as I'm aware, though, nobody outside of research settings is checking GLP-1 or GIP blood levels. Still, it appears to suggest that responses to a given drug can differ based on someone's starting glp or gip levels, even though the reason behind that is a bit tough for me to grasp. The body's natural amounts of these hormones are tiny next to what GLP-1 medications do, so it surprises me somewhat that baseline readings would carry any weight at all. Without first testing levels, is there any practical use? Perhaps it makes sense for people who don't do well on their first glp drug to experiment with another, and maybe even to give semaglutide a shot when tirzepatide isn't working well, though that thought stings a little considering how awful my own experience with it was. Even so, I'd still say tirz or reta is the better place to begin.
Click to expand...
Your weight loss numbers leave me stunned, LessGuy!
 
lessthanhalf said:

tubby said:

lessthanhalf said:

For me, it's tough to see what a GLP drug gains by leaving out GIP agonism. GIP agonism works against the side effects that come from GLP-1, which means either fewer side effects or a higher maximum tolerated dose, and that makes the drug work better. There will be people who barely get side effects at all, so for them it may not matter much. But when you look at the average, the GIP in reta should make it better both for weight loss and for cutting liver fat, while causing fewer side effects, compared with a glucagon/GLP-1 agonist.
Click to expand...
There is also a fairly intriguing study that could shift how you view that position:


https://www.mdpi.com/2075-4418/16/13/1979
Click to expand...
That caught my eye too, and there is certainly something intriguing there. As far as I'm aware, though, nobody outside of research settings is checking GLP-1 or GIP blood levels. Still, it appears to suggest that responses to a given drug can differ based on someone's starting glp or gip levels, even though the reason behind that is a bit tough for me to grasp. The body's natural amounts of these hormones are tiny next to what GLP-1 medications do, so it surprises me somewhat that baseline readings would carry any weight at all. Without first testing levels, is there any practical use? Perhaps it makes sense for people who don't do well on their first glp drug to experiment with another, and maybe even to give semaglutide a shot when tirzepatide isn't working well, though that thought stings a little considering how awful my own experience with it was. Even so, I'd still say tirz or reta is the better place to begin.
Click to expand...
What stood out most to me: a subset of patients will respond better to sema than to tirz. When we only look at population-level averages—where tirz comes out ahead—that minority can end up underserved.

Once glucagon-agonism enters the picture, it's plausible that this same subset could respond better to survo. I share the view that we can't identify who they are, given that testing isn't being done, yet it does seem such people are out there.
 
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