# The likely first longevity drug is based on sketchy science. This is bad for science and bad for longevity.

If you are interested in the longevity scene, like I am, you probably have seen press releases about the dog longevity company, Loyal for Dogs, getting a nod for efficacy from the FDA. These have come in the form of the New York Post calling the drug "[groundbreaking](https://news.google.com/articles/CBMidWh0dHBzOi8vbnlwb3N0LmNvbS8yMDIzLzEyLzEwL2xpZmVzdHlsZS9ncm91bmRicmVha2luZy1hbnRpLWFnaW5nLWRydWctZm9yLWRvZ3MtbW92ZXMtY2xvc2VyLXRvLWdhaW5pbmctZmRhLWFwcHJvdmFsL9IBeWh0dHBzOi8vbnlwb3N0LmNvbS8yMDIzLzEyLzEwL2xpZmVzdHlsZS9ncm91bmRicmVha2luZy1hbnRpLWFnaW5nLWRydWctZm9yLWRvZ3MtbW92ZXMtY2xvc2VyLXRvLWdhaW5pbmctZmRhLWFwcHJvdmFsL2FtcC8?hl=en-US&gl=US&ceid=US%3Aen)", Science Alert calling the drug "[radical](https://news.google.com/articles/CBMiVGh0dHBzOi8vd3d3LnNjaWVuY2VhbGVydC5jb20vYS1yYWRpY2FsLW5ldy1kcnVnLWlzLXBvaXNlZC10by1leHRlbmQtdGhlLWxpZmUtb2YtZG9nc9IBAA?hl=en-US&gl=US&ceid=US%3Aen)", and the more sedate New York Times just asking, "Could Longevity Drugs for Dogs Extend Your Pet's Life?", presumably unaware of Betteridge's Law of Headlines. You may have also seen the coordinated Twitter offensive of people[ losing their shit about this](https://twitter.com/celinehalioua/status/1729525718827274642), including their lead investor, Laura Deming, saying that she "[broke down crying when she got the call](https://twitter.com/LauraDeming/status/1729529895347515443)".

And if you have been following Loyal for Dogs for a while, like I have, you are probably puzzled by this news. Loyal for Dogs has been around since 2021. Unlike any other drug company or longevity company, they have released almost zero information (including zero publications) about their strategy for longevity. It's surprising, to say the least, to see a company go from zero information to efficacy nod, because, well, what are you basing your efficacy on? How did you recruit your patients and veterinary partners to help you with efficacy? Did you make them all sign some incredibly airtight NDAs? If so, why?

These thoughts swirling around my head, I waded through the press releases trumpeting the end of dog death as we know it in order to figure out what exactly Loyal is doing for dog longevity. And, what I found first surprised me, then saddened me. Loyal did not prove efficacy in dog longevity. They found a path around the FDA instead. That's the surprising part. The sad part is that, in doing so, they relied on some really sketchy science. And I think that, based on their trajectory, they won't just be the first company to get a drug approved for longevity. They will be the first one to get a longevity drug pulled for non-efficacy as well, and put the field back years.

So let's start with how they got their drug approved in the first place. Well, they didn't. To get drugs approved in animals, you need to prove three things: efficacy, safety, and manufacturing consistency. Normally, efficacy is the hardest part of this, because you have to prove to the FDA that your drug cures the disease that it's supposed to. This is especially hard in aging, because any aging trial would take a long time. Loyal found a way around that. If you can instead prove to the FDA that it would be too difficult to test your animal drug for efficacy before releasing it, they allow you to sell the drug first, and prove the efficacy later. This is a standard called "reasonable expectation of effectiveness".

So, what exactly did Loyal show to the FDA to prove that there was a reasonable expectation their drug would be effective in aging? Well, it's hard to tell, because, again, Loyal has released very little data. But, based on the NYT article and[ their blog post](https://loyalfordogs.com/posts/loyal-announces-historic-fda-milestone-for-large-dog-lifespan-extension-drug), I can sketch out a basic idea of what they did.

Loyal's longevity drug is an injectable insulin-like growth factor 1, or IGF-1, inhibitor. As the name suggests, IGF-1 is closely related to insulin and is regulated by insulin. Also as the name suggests, IGF-1 causes things to grow. High IGF-1 causes acromegaly, the condition that makes people look like storybook giants.

Loyal gave their IGF-1 inhibitor to healthy laboratory dogs (and possibly diabetic dogs, although it's hard to tell). Lo and behold, it lowered IGF-1. It probably also reduced insulin. They then looked at healthy pet dogs, and found that big dogs had higher levels of IGF-1, which is one of the reasons they're big. Small dogs had lower levels of IGF-1. Small dogs, as we all know, live longer than big dogs. Therefore, Loyal said, our IGF-1 inhibitor will extend the life of dogs.

Needless to say, this is bad science. Really bad science. There are holes big enough in this to walk a Great Dane through, which I'll talk about in a sec. Apparently, though, this reasoning was good enough for the FDA. So, Loyal got their "reasonable expectation of effectiveness" nod. Cue fanfare and crying and me being surprised.

Ok, so that's how they did it. But...why did they do it? No wait, that's an easy one. Money. Sorry. Ok, better question: should we believe them?

No! God, no. Their reasoning is terrible! Correlation does not equal causation! Just because small dogs have lower levels of IGF-1 and live longer does not mean that lower levels of IGF-1 cause dogs to live longer! And, even if they did, there's no reason to believe that lowering levels of IGF-1 would reverse any of the "damage" caused by high levels of IGF-1! The big dogs will still be big!

And, actually we can even go further than that. Not only is Loyal's reasoning wrong, their facts are wrong as well. Let's look at some of the claims in their blog post, shall we?

They say

"In large- and giant-breed dogs, breeding for size caused these dogs to have highly elevated levels of IGF-1, a hormone that drives cell growth. High IGF-1 effectively drives these dogs to grow large when they’re young, but high IGF-1 levels in adult dogs are believed to accelerate their aging and reduce their healthy lifespan." Then they put this "figure".

![](https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dogs-IGF-1-eigenmann-et-al-1984-Maxwell-et-al-1998-1024x576.jpg)

This figure, although attractive, is misleading at best. IGF-1 contributes to body size in dogs, but it's not a straightforward relationship. Like, look at this figure from[ Connecting serum IGF-1, body size, and age in the domestic dog](https://sci-hubtw.hkvisa.net/10.1007/s11357-010-9182-4) (2011). 

![](https://39669.cdn.cke-cs.com/rQvD3VnunXZu34m86e5f/images/67e4709ea6d298a09d3cad1dfa0669243d51a9f3735abec5.png)

This is, granted, a less attractive graph than Loyal's. Theirs has cute little figures of dogs and this one just has black squares. But, this is way more recent and based on 88 dogs. Their references, which I can't find (and they didn't even provide proper citations for), are from 1984 and 1998, and based on an unclear number of dogs. I am more inclined to trust this graph.

And what does it say? Well, that IGF-1 levels do tend to go up with increasing bodyweight, but it's not a straightforward relationship. Among dogs with bodyweight around the 20-30 pound mark, it looks like IGF-1 levels can vary from 20-ish to close to 300 ng/mL. Now, could I cherry pick and find a small dog with a low level of IGF-1 and a big dog with a high level of IGF-1 and say "big dogs have up to 28x the level of IGF-1 of small dogs"? Yes, I could. But that would be incredibly misleading.

Meanwhile, if we look at the exact same paper, we also get this data on the relationship between IGF-1 and age in dogs.

![](https://39669.cdn.cke-cs.com/rQvD3VnunXZu34m86e5f/images/96f2ed120a2b1757e81befc91a7162c3378805329e67af05.png)  
 

Hm...let's see what we think of the idea that low levels of IGF-1 are associated with longer lifespans. Well, based on the fact that there are plenty of 12+ year old dogs with IGF-1 levels at the 100+ ng/mL mark, I'd say that relationship also seems pretty weak. I mean, sure, the highest levels of IGF-1 are in puppies, but the 4th highest IGF-1 level is in a dog that's over 16, and the 5th highest is in a dog that's like 12.5.

So, not only should Loyal definitely not say that "high IGF-1 levels accelerate dog's aging", but they shouldn't even really say that they're strongly associated with them. It's a weak correlation at best (r=.0677).

I hope you now see why I think this longevity drug ironically doesn't have long to live. There's no way, given the data, that this drug will cause dogs to live longer. It may, however, cause dangerous side effects in dogs. IGF-1 inhibitors do in humans (oh, did I forget to mention that IGF-1 inhibitors have existed for humans for decades, and they have zero evidence of being longevity drugs? My bad. Now I have). IGF-1 inhibitors can cause[ low levels of blood platelets, elevated liver enzymes, and hyperglycemia](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093917/). Hopefully, if this drug does cause harmful effects in dogs, it will be caught in the safety trials and the drug won't be released.

But, even if the drug is safe, it will be a waste of time and a waste of money for dog owners to give it to their pets. This drug should have never made it this far, and, if it does get actually approved, it's going to spectacularly fail its actual efficacy trials and bring a lot of legitimate longevity companies down with it.

And, for the record, I know I'm not the only one that thinks this. I've had multiple conversations with other aging-adjacent people who also think this. But nobody is willing to stick out their neck and actually call Loyal out. I mean, hell, I'm writing this anonymously and I'm still a little nervous. But, I'll say it here and now: the dog emperor has no clothes.