The Emerging Role of Amylin: Dr. Garvey on CagriSema and the Future of Obesity Care

Home Obesity The Emerging Role of Amylin: Dr. Garvey on CagriSema and the Future of Obesity Care Timothy Garvey, MD, of the University of Alabama at Birmingham, reviews the latest data on CagriSema and emerging amylin-based therapies pr

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The Emerging Role of Amylin: Dr.

Garvey on CagriSema and the Future of Obesity Care Timothy Garvey, MD, of the University of Alabama at Birmingham, reviews the latest data on CagriSema and emerging amylin-based therapies presented at the 2026 ADA Scientific Sessions.

Dr.

Garvey explains how combining amylin and GLP-1 receptor agonism may enhance weight loss and glycemic control while maintaining tolerability, and explores the potential role of amylin therapies in the future management of obesity and type 2 diabetes.

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Transcript What is the biggest takeaway for clinicians from the CagriSema data presented at the 2026 ADA Scientific Sessions?

Dr.

Garvey: Yeah, well, I think that the foremost aspect of this is the efficacy.

This is a CagriSema, as you know, a combination of the GLP-1 receptor agonist semaglutide plus the long-acting amylin cagrilintide, so two different mechanisms of actions, two different compounds both affecting appetite in an additive way.

So you add the cagrilintide to the semaglutide, you get additive weight loss into a very nice range of efficacy.

And the thing about the cagrilintide, ’cause we’re all worried about tolerability, it’s very well-tolerated compared to the GLP-1.

So when you add it to the semaglutide, you get increased efficacy with minimal worsening of side effects.

So I think that’s the major message as far as I’m concerned.

How does amylin complement GLP-1 therapy, and why is that combination generating so much interest?

Dr.

Garvey: I think these are both nutrient-stimulated hormones, you know.

Amylin is a natural hormone released from beta cells in the pancreas, of course, GLP-1 from the GI tract.

They both travel to the brain and interact with centers regulating caloric intake.

They activate some overlapping populations of neurons, but separate neurons, which, I think, is the basis for their additive effect.

Of course, these are short-lived.

As natural hormones, the GLP-1 and amylin are short-lived.

So, of course, to make them druggable for weekly injections, they’re modified for a longer half-life in the circulation.

So they’re both injected at the same time in a dual-chamber pen.

So both compounds go in one right after the other at the same with one injection.

Of course, whenever you’re activating GLP-1 receptors in the hypothalamus to suppress appetite, you’re also activating the same receptors in the area postrema, which mediates some of the nausea and GI symptom formation, so that’s still there.

But the cagrilintide doesn’t seem to have that same pronounced effect to activate these neurons that are responsible for GI symptomatology.

So again, there’s a molecular basis for the additive increased efficacy without worsening of the side effect profile.

Which patients with type 2 diabetes stand to benefit most from CagriSema based on the REIMAGINE results?

Dr.

Garvey: Yes.

I think, with diabetes, type 2 diabetes, with any intervention really, these patients lose less weight than if they just had obesity alone without diabetes.

But yet they have two diseases in essence, and we not only need to get the weight loss that will improve glycemic control, but we need the weight loss that will address many other obesity-related complications that even patients without diabetes will have.

So we need to get that weight loss in the range of, in many patients, in the range of 15% or so, to address the obesity-related complications.

CagriSema has a very nice efficacy in that regard in type 2 diabetes.

We’re getting over 15% weight loss in patients with type 2 diabetes.

There’s not many drugs that are around that will do that.

And so this is, I think, the promise.

I think there’s particularly an advantage of CagriSema in patients with type 2 diabetes for that reason.

And of course, the hemoglobin A1C control is outstanding.

I mean, we’re reaching hemoglobin A1C targets, you know, 6.5% or less.

Even normal hemoglobin A1C is 5.7% or less.

And the important thing there is we’re reaching these targets with minimal or no hypoglycemia.

And if there is hypoglycemia, it’s almost always patients on medicines like sulfonylureas, which are prone to a hypoglycemia anyway.

So they’re very safe, outstanding for glycemic control.

And CagriSema also reaches the amount of weight loss we need in many patients with both obesity and diabetes for the obesity-related complications.

Do the ADA data suggest that amylin-based therapies could become a major new treatment class in obesity and diabetes care?

Dr.

Garvey: Yes, in my opinion, of course, there’s no long-acting amylins approved right now that we can take to the clinic, but they’re in phase 3 trials.

I think I would point out there’s one, eloralintide, from Eli Lilly.

There’s cagrilintide, as we’ve already discussed, Novo Nordisk, and there’s others, petrelintide from Zealand, Roche.

These all achieve moderate weight loss as a monoagent, but, you know, between 10 and 20% weight loss, usually around, you know, 13, 14% weight loss, somewhere in there.

They’re very well-tolerated.

They have about half the rates of nausea as GLP-1s, and rates of vomiting, diarrhea, and constipation that really approach placebo.

They’re much better concentrated.

Rates of drug discontinuation due to side effects are very, very low.

So I think the promise here is a medication that gives us moderate weight loss, which is sufficient in the majority of our patients to improve their health, to meet our patients’ needs for weight loss, to meet our health goals in terms of preventing and treating obesity-related complications with a well-tolerated medication.

I think the way this will evolve in the future is algorithmic care like we do with diabetes.

We start out with one drug to try to get glycemic control.

If it works, fine.

If not, we can add another drug to it.

And I think with obesity, it might work the same way once we have greater numbers of choices in the clinic.

We will wanna start out with a drug that is well-tolerated by patients that has every likelihood of achieving the weight loss we need clinically.

A long-acting amylin could fit that bill.

I think it’s a drug that primary care will have an easier time with than a GLP-1 that is more prone to these side effects.

But then if that’s not sufficient, then we can add a GLP-1 to that, you know, in a step sort of way.

On the other hand, if you have patients with very high BMI that are having maybe mobility problems, then you really wanna get more powerful weight loss medications.

You wanna go with your dual and triple agonist in those patients.

And I might also add a caveat.

Those patients that have complications that have been shown to be ameliorated by GLP-1-based drugs, and I would say secondary prevention of cardio, of heart attacks for semaglutide.

I would say treating MASH with semaglutide.

It’s phase 3 trial showing efficacy there, not where the primary outcome is the improvement of the complication.

The same is true with tirzepatide and sleep apnea.

If a patient has those complications, then I would go straight to the GLP-1 based drug where the evidence there for improvement.

But that’s not the majority of patients.

The majority of patients living with obesity do not have those complications.

So I view amylin as emerging, as a very attractive first-line medication for many, many patients.

Dr.

Garvey: Well, I think, you know, it’s early on.

You know, we have many more coming into clinical trials.

I think eventually we’re going to need to do complication-specific clinical trials, as I mentioned, where it’s the improvement in the complication is the primary outcome measure, not amount of weight loss per se.

Those trials aren’t there with the long-acting amylins, but there’s a lot of preclinical data that is very interesting with these amylins.

If it translates over into human physiology and pharmacology, I think this is gonna be very exciting.

I’ll just point out a few of those things.

One, amylin agonists that also activate the calcitonin receptor.

Many of them do.

And we used to use a calcitonin, salmon calcitonin.

We still do to treat osteoporosis.

And we know there’s bone loss that accompanies weight loss with these medications.

So this is a potential medication that could produce the weight loss and still preserve bone.

And that might translate into reduced falls and fractures, you know, way down the line.

So that’s something we need to think more about.

We also know that it preserves muscle mass to a relative degree at the expense of losing fat more proportionately.

So if you can preserve the muscle mass, of course that might increase functionality, but it could also have health benefits in terms of improving insulin sensitivity since muscle is the major tissue that accounts for insulin-mediated glucose uptake, and also it increases energy expenditure because of the muscle mass.

So that might help preserve the weight loss, sustain weight loss over a longer period of time.

You know, things like that, I think it’s gonna be very exciting to see.

That’s true in preclinical research.

But again, we can’t assume that’s true in humans, but I think those are hypotheses we can definitely test.

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Peptides referenced: Semaglutide, Tirzepatide, Cagrilintide, Amylin, Calcitonin (Salmon), Eloralintide, GLP-1.