MariTide

Here2Learn

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Found this quote interesting in the new study on MariTide. This is from The NY Times article behind a paywall.

“Dr. Bradner said the company decided to block GIP because it had genetic data from Iceland indicating that people who had a variant that stops GIP from working were naturally thinner.”


Whole document:

The pharmaceutical manufacturer Amgen announced on Tuesday that an experimental obesity drug helped patients lose up to 20 percent of their weight in a year. The drug, MariTide, is given by injection once a month, compared with once a week for other obesity drugs like Wegovy and Zepbound that are already on the market.

Those drugs have stunned longtime obesity researchers, who had all but given up on ever seeing safe and effective weight loss drugs. Now, dozens of similar drugs are in development, as companies try to improve on the current ones. Amgen’s is among the first to show what might be possible.

The data came from a Phase 2 trial testing effectiveness as well as safety. It involved nearly 600 people divided into two groups, one with adults who were obese or overweight, and another with patients who also had Type 2 diabetes.

The drug still must go through additional clinical trial phases involving many more patients, and then receive approval from the Food and Drug Administration before being sold to patients. The company has yet to set a price for the drug and did not lay out a timeline for when the drug may become available.

Amgen also did not provide detailed data — that will come in later in a peer-reviewed study and will be presented at a meeting, the company said. Instead, to meet requirements of the federal Securities and Exchange Commission, it provided so called top-line data that could affect its stock price.

Dr. Jeffrey Flier, a diabetes and obesity researcher at Harvard, said the results were “promising,” adding that MariTide “could be a future player in a highly competitive market.”

Dr. Jay Bradner, the company’s chief scientific officer, noted a surprising effect of the drug: When the trial ended, many participants maintained their weight loss for as long as 150 days. That means that less frequent injections could be possible or even that patients may not need to stay on the drug permanently. The company said it was studying quarterly injections.

The patients in the Amgen study who had Type 2 diabetes lost up to 17 percent of their initial weight. That is consistent with findings involving other obesity drugs — people with diabetes tend to lose less weight.

Dr. Bradner also noted that weight loss with the drug did not plateau at 52 weeks. That raises the possibility, he said, that patients may continue to lose weight if they take the drug for a longer time.

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The Amgen drug acts differently from the main obesity drugs that are currently being sold, Wegovy by Novo Nordisk and Zepbound from Eli Lilly. Those are molecules that bind to a protein on the surface of cells that responds to the gut hormone GLP-1.

But MariTide is different in its structure and function. It is an antibody and, as is typical of those molecules, it lasts longer in the body.

MariTide resembles the earlier drugs because it binds to GLP-1 receptors, using two peptides that stick out from its surface. But it differs in a surprising way because it also blocks the effects of another gut hormone known as GIP. Researchers had thought that the way to make an obesity drug was to activate GIP, not to block it.

Dr. Bradner said the company decided to block GIP because it had genetic data from Iceland indicating that people who had a variant that stops GIP from working were naturally thinner.

Why MariTide is effective remains a mystery. Eli Lilly’s drugs — Mounjaro, for diabetes, and Zepbound, for obesity — activate GIP. So why would Amgen’s new drug work so well?

The company wants to know, too. So it is sponsoring Randy Seeley, director of the University of Michigan’s obesity and nutrition research center, to study mice to try to figure it out.

“It’s weird,” Dr. Seeley said. “It doesn’t fit most of our ideas about how biology is supposed to work.”

Gina Kolata reports on diseases and treatments, how treatments are discovered and tested, and how they affect people. More about Gina Kolata

A version of this article appears in print on Nov. 27, 2024, Section A, Page 15 of the New York edition with the headline: New Amgen Obesity Drug Causes 20% Weight Loss. Order Reprints | Today’s Paper | Subscribe See more on: Amgen Inc. Share full article
 
I think this particular arm of the "GLP" class of drugs will end badly. GIP receptors appear to play a role in preventing heart remodeling, and even reversing it.

While the people with a mutation causing them to lack GIP receptors, and therefore always thin, may not have a problem with heart remodeling because their hearts aren't stressed, it could be a disaster to give this to overweight people already putting excess pressure on their heart, blocking the natural GIP action that slows harmful changes to heart, and removing the very thing protecting them from having that from happening more quickly.

The same dynamic could make this even more damaging for bodybuilders, already susceptible to left ventricular hypertrophy.
 
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I think I was more interested in the point they are finding genetic reasons some people are thinner naturally than others. Thinner does not mean healthier as we all know. We just have so much we still don’t know about our own dna I find it fascinating.

They've got a lot of the relevant genetic markers down for GLP, Essentially. if you're genetically predisposed to not producing enough GLP hormone, or are genetically predisposed to be insensitive to the hormone, you're much more likely to be overweight.

A lot of bodybuilders understand how low, or high testosterone levels lead to certain behaviors, so I've always hoped the parallel to what are essentially other behavioral influencing hormones would be easy to understand.

 
They've got a lot of the relevant genetic markers down for GLP, Essentially. if you're genetically predisposed to not producing enough GLP hormone, or are genetically predisposed to be insensitive to the hormone, you're much more likely to be overweight.

A lot of bodybuilders understand how low, or high testosterone levels lead to certain behaviors, so I've always hoped the parallel to what are essentially other behavioral influencing hormones would be easy to understand.

I would love to do the test, just not ready to shell out the money for it yet.

As for the genetic identifiers I am thinking a lot bigger than just GLP’s. I just think every added link in the chain helps drives medicine and understanding forward. Specific to GLP’s I think it is great because they are studying women more than I believe they ever have.
 
Didn’t realize the test you were referring to was just for obesity. I was thinking the sequencing type of dna test. Didn’t realize they have a specific test for obesity.
 
I'm surprised insurance companies aren't mandating the test as a reason to deny coverage. "Not likely to work for you".
Great point, they usually don’t miss an opportunity like that. Of course I had an autoimmune panel done and they don’t cover it because it is considered experimental.
 
With once monthly administration, what if you don't like the sides? How long do you have to suffer until it gets out of your system.

I had similar doubts about once weekly GLP1s but was proven wrong. Hopefully here too.
Couldnt you just have a suuper low start dose to off set this?
Obviously, I guess, the first few to find that first dose could suffer for the greater good.
I would love once a month stuff, for everything.. but then again I havent taken the jump with trt away from test C.
 
Early research shows this drug leads to bone loss though.. lol

Yeah, this is why their stock tanked. They may be able to fix this though since there are a lot of studies happening around the coadministration of other drugs to preserve bone and muscle. I almost applied for a study of Bremelanotide and Tirzepatide, but noted out once I realized what Bremelanotide is normally used for

Anyway, I think a GLP-1 that lasts this long is a bad idea. Have no clue what they'll do once the first month long adverse reaction is reported.
 
Yeah, this is why their stock tanked. They may be able to fix this though since there are a lot of studies happening around the coadministration of other drugs to preserve bone and muscle. I almost applied for a study of Bremelanotide and Tirzepatide, but noted out once I realized what Bremelanotide is normally used for

Anyway, I think a GLP-1 that lasts this long is a bad idea. Have no clue what they'll do once the first month long adverse reaction is reported.
Same reason I have never considered experimenting with setmelanotide. That being said, If I'm neither ill or dying, I'll never submit myself for any monoclonal antibody research. The margins are always tight.
 
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