Eli Lilly's Unnamed Quintuple Agonist: Exploring Amylin and Calcitonin

nukatide

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View: https://youtube.com/shorts/SNsfuu5V8nU?si=KwtxDgSRwdtkJ4Y9

It seems there's no official name yet. However, Eli Lilly appears to be targeting both satiety and bone health. Has anyone come across Amylin or Calcitonin? These seem to be the latest components added alongside the advantages of GLP1, GIP, and Glucagon that are present in Retatrutide.

From a quick, superficial look, Amylin appears to provide satiety comparable to Cagrilintide. Additionally, Amylin further delays gastric emptying, enhances bone metabolism (which essentially refers to the remodeling of bone tissues to boost skeletal strength), and oddly, Amylin inhibits Glucagon. I find this odd since Glucagon is included in the same formulation. My take is that the suppression of Glucagon isn't an added benefit of Amylin but simply a side effect. I think Glucagon is naturally generated during fasting or intense exercise. Since you're supplementing with Glucagon, you'll keep enjoying its benefits. Calcitonin essentially instructs the body to reduce blood calcium levels and safeguard bone density.
 
Based on only the most preliminary information I've come across, Amylin appears to provide a satiety effect comparable to that of cagrilintide.
 
nukatide said:

View: https://youtube.com/shorts/SNsfuu5V8nU?si=KwtxDgSRwdtkJ4Y9

It seems there's no official name yet. However, Eli Lilly appears to be targeting both satiety and bone health. Has anyone come across Amylin or Calcitonin? These seem to be the latest components added alongside the advantages of GLP1, GIP, and Glucagon that are present in Retatrutide.

From a quick, superficial look, Amylin appears to provide satiety comparable to Cagrilintide. Additionally, Amylin further delays gastric emptying, enhances bone metabolism (which essentially refers to the remodeling of bone tissues to boost skeletal strength), and oddly, Amylin inhibits Glucagon. I find this odd since Glucagon is included in the same formulation. My take is that the suppression of Glucagon isn't an added benefit of Amylin but simply a side effect. I think Glucagon is naturally generated during fasting or intense exercise. Since you're supplementing with Glucagon, you'll keep enjoying its benefits. Calcitonin essentially instructs the body to reduce blood calcium levels and safeguard bone density.
Cagrilintide is, in fact, amylin—more precisely, an amylin analog. The only difference is that it has been modified for extended duration. Yet in every practical sense, the two are identical.
 
They'll surely push for this to be labeled a biologic too — gotta safeguard those profit margins!
 
Rolltide61 said:

We should send this over to the vendors immediately so they can copy it. That's on us to make happen.
Your risk tolerance is a lot higher than mine. With these increasingly elaborate structures, I have less and less faith that fly-by-night Chinese labs can actually make the real thing — rather than some isomer that slips through routine testing while being a distinct molecule. When vendors hide who manufactured the API (and those vendors are sourcing from finishers who chase the cheapest API that will clear lab tests), a source you believe is dependable might still differ from one batch to the next at the same vendor.
 
nukatide said:

View: https://youtube.com/shorts/SNsfuu5V8nU?si=KwtxDgSRwdtkJ4Y9

It seems there's no official name yet. However, Eli Lilly appears to be targeting both satiety and bone health. Has anyone come across Amylin or Calcitonin? These seem to be the latest components added alongside the advantages of GLP1, GIP, and Glucagon that are present in Retatrutide.

From a quick, superficial look, Amylin appears to provide satiety comparable to Cagrilintide. Additionally, Amylin further delays gastric emptying, enhances bone metabolism (which essentially refers to the remodeling of bone tissues to boost skeletal strength), and oddly, Amylin inhibits Glucagon. I find this odd since Glucagon is included in the same formulation. My take is that the suppression of Glucagon isn't an added benefit of Amylin but simply a side effect. I think Glucagon is naturally generated during fasting or intense exercise. Since you're supplementing with Glucagon, you'll keep enjoying its benefits. Calcitonin essentially instructs the body to reduce blood calcium levels and safeguard bone density.

Honestly, calling it a quintuple agonist feels like a marketing trick more than anything else—calcitonin agonism doesn't do anything for weight loss, and it might even work against it.

Take cagri: it's a double agonist hitting amylin 1/3 and calcitonin, yet its weight loss efficacy is only about 50% of what eloralintide achieves, and eloralintide is 100% specific to amylin 1/3. That tells me calcitonin is irrelevant here, both biochemically and clinically.

That said, the molecule itself is a curiosity. How did they pull it off, given how different the structures of amylin and glp-1/gip/gcgr are? Seeing it in a crystal structure would be fascinating.
 
tubby said:

Rolltide61 said:

We should send this over to the vendors immediately so they can copy it. That's on us to make happen.
Your risk tolerance is a lot higher than mine. With these increasingly elaborate structures, I have less and less faith that fly-by-night Chinese labs can actually make the real thing — rather than some isomer that slips through routine testing while being a distinct molecule. When vendors hide who manufactured the API (and those vendors are sourcing from finishers who chase the cheapest API that will clear lab tests), a source you believe is dependable might still differ from one batch to the next at the same vendor.

I'm with you on that. From what I recall, reta and tirz each contain a stereocenter, and as you pointed out, that's something mass spec won't pick up. So it's possible we're all receiving a racemic mix—honestly, I have no idea. If anyone has deeper knowledge on this, I'd really like to hear it.

Could that also explain why eloralintide hasn't hit the market? It has far more non-natural amino acids, stereocenters, and a disulfide bond. I'm just guessing. Cagri also features a disulfide bond, yet that doesn't appear to cause issues there. If anyone can shed light on the reason, please do!
 
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