Happy Monday!
I read a lot of papers to stay up to date on what is going on in the space. Most of it is noise, but every now and then something makes me stop and read it twice.
Last week that was a drug called eloralintide.
It showed up in a new Lancet trial and in a discovery paper from Eli Lilly. I went through both. The more I read, the more it stuck with me as a potential player in the fat loss peptide world.
Here is what I found.
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What It Is
Eloralintide is a once-weekly injectable drug from Eli Lilly (although I’m sure it will be better to split the dose).
It used to go by the code name LY3841136. It is still investigational, so it lives in clinical trials and is not approved for anything.
What caught me is the mechanism. This one is an amylin drug, not a GLP-1.
Amylin is a hormone your pancreas puts out alongside insulin after a meal. Its job is to signal to your brain that you are full.
It does that through a small patch of the brainstem called the area postrema, which is a distinctly different part of the brain than the one your GLP-1 acts on.
So this is a fullness signal coming from a completely different direction.
The Benefits
The weight loss in trials so far is substantial and increases with dose.
The tolerability is the part that has people talking. Less nausea and vomiting than you would expect from something that shuts down appetite.
When it comes to engineering weight loss peptides, killing appetite is the easy part.
Doing it without making people miserable is the hard part.
Lilly is betting they can pull off both.
Clinical Data
The main study is a Phase 2 trial in The Lancet. 263 adults, 46 sites across the US, 48 weeks long.
Average weight loss ranged from about 9% on the low dose to right around 20% on the high dose. The placebo group lost 0.4 percent.
20% in under a year is tirzepatide-level weight loss. And this came without the help of a GLP-1.
The main side effects were nausea and fatigue. Mostly mild to moderate. Worse at higher doses, and better when people titrated up slowly.
A few caveats, because they matter.
This is still Phase 2. The group was mostly women, mostly White, average BMI around 39. We have no long-term data yet. No Phase 3 results yet either. Lilly says Phase 3 is starting now.
Elora vs. Cagri
You have probably heard of cagrilintide by now. That is Novo Nordisk's amylin drug, the one they pair with semaglutide in CagriSema.
The difference comes down to selectivity.
Cagrilintide is non-selective. It hits the amylin receptor and the calcitonin receptor.
Eloralintide is selective. It mostly sticks to the amylin receptor and leaves the calcitonin receptor alone.
The calcitonin receptor is what makes your stomach turn.
Skip it, and you may keep the appetite control without as much of the gut trouble. Lilly's whole bet here is selectivity for a cleaner ride.
My guess is that you would also probably get less of the poor mood effects many people report when using cagrilintide.
The Future
Because amylin and GLP-1 work through different parts of the brain, you can run them together.
They are not fighting over the same receptor. Your GLP-1 works mostly through the vagus nerve and the hypothalamus.
Amylin works through the area postrema. Two separate systems, both pushing in the same direction.
That opens up a couple of possibilities.
One is stacking it on top of a GLP-1, such as tirzepatide or retatrutide.
You get appetite control from two angles instead of one. Lilly is already running a Phase 2 trial of eloralintide with tirzepatide.
The other one is what really has my attention.
Picture using something like this on an off-cycle. You step off your GLP-1 for a stretch.
Normally your appetite comes screaming back. A drug that works through a separate pathway could hold that line while your GLP-1 receptors get a rest.
Final Thoughts
I have not used eloralintide.
And I cannot tell you where to buy it, so don’t ask!
But the use case is one of the more interesting things I have read all year.
It appears to be a clean, once-weekly appetite drug that works on a completely different system than every GLP-1 out there.
Something you might stack with your GLP-1, or lean on to get through an off-cycle.
I will keep reading as the trials come out. When there is more worth sharing, you will get it here first.
Have a fantastic week!
Best,
Hunter Williams
Further reading