6 Things to Know About GLP-1 vs. Amylin for Weight Loss

Glucagon-like peptide-1 (GLP-1) medications, such as Wegovy (semaglutide), have opened new doors when it comes to losing excess body weight and treating Type 2 diabetes. GLP-1s act like incretins, which are natural gut hormones that help regulate digestion and blood sugar (glucose). But another hormone, called amylin, may offer a new target for these health conditions.

So what’s the difference between GLP-1 and amylin? And what happens when you combine them? Let’s take a look at the key similarities and differences between amylin versus GLP-1.

1. GLP-1 and amylin are made in different areas of the body

GLP-1 and amylin are both hormones that help regulate digestion, appetite, and blood sugar. But they come from different parts of your body.

GLP-1 is released mainly by your gut (intestines). Your body releases GLP-1 after you eat.

Amylin, on the other hand, is made mainly by your pancreas. This is the same organ that makes insulin. In fact, amylin and insulin are released together after you eat.

Just like with insulin, people living with Type 1 diabetes typically produce little to no amylin. Type 2 diabetes, on the other hand, is associated with high levels of amylin. Too much amylin can form plaques (clumps) and damage the pancreas.

2. GLP-1 and amylin work in slightly different ways

GLP-1 and amylin both regulate your appetite and blood sugar. But they don’t work in exactly the same way.

GLP-1 activates GLP-1 receptors in the body. This has several different effects, including:

• Increasing insulin release from the pancreas

• Reducing sugar production by the liver

• Slowing down the passage of food through your digestive system

• Reducing food cravings and appetite

Amylin bonds to amylin receptors in the body. This has similar effects to GLP-1: It also slows down the passage of food through the stomach and lowers blood sugar levels. But it also has two main effects that are different from GLP-1:

• Amylin activates an area of the brainstem that helps you feel satisfied sooner when eating.

• Amylin can improve sensitivity to a hormone called leptin. This helps reduce appetite and increase fat metabolism.

3. GLP-1 and amylin affect blood sugar differently

GLP-1 helps the pancreas release more insulin when blood sugar levels are high. Insulin moves glucose out of your bloodstream and into your cells to lower blood sugar levels. GLP-1 also reduces the release of glucagon, a hormone that tells your liver to release sugar into your blood.

Amylin affects blood sugar differently. It doesn’t increase insulin levels. Instead, it helps manage the rise in blood sugar after meals by slowing stomach emptying and reducing glucagon release.

Because of this difference, GLP-1 and amylin-based medications are used differently to treat diabetes. Since they have a greater effect on blood sugar levels, Ozempic (semaglutide) and other GLP-1 medications are approved to treat Type 2 diabetes on their own. But Symlin (pramlintide), the only FDA-approved amylin-based medication, is only used as an add-on treatment. It can help people living with diabetes whose blood sugar isn’t controlled well with just insulin. But Symlin isn’t approved as a stand-alone diabetes treatment.

Good to know: New medications that combine GLP-1 and amylin-based medications may work even better for Type 2 diabetes than either ingredient on its own. But there isn’t an FDA-approved combination product yet. 

4. GLP-1 medications are more established for weight loss than amylin medications

GLP-1 medications have a much longer track record as prescription treatments for weight management. These include:

• Wegovy

• Foundayo (orforglipron)

• Zepbound (tirzepatide); which also mimics glucose-dependent insulinotropic polypeptide (GIP), another incretin hormone

Amylin medications aren't as established for this purpose. High levels of amylin can form damaging plaques in the body. So it’s taken longer for researchers to develop amylin-based medications that don’t cause this problem.

There currently aren’t any amylin-based medications approved for weight management. Several are currently in clinical trials. So far, amylin-based medications on their own don’t seem to work as well for weight loss as GLP-1 medications. But combination products that combine the two seem to work better than either medication alone. The role that newer amylin medications may play in weight management will depend on clinical trial results and FDA approval.

5. Combining GLP-1 and amylin medications may lead to greater weight loss

Since GLP-1 and amylin control appetite and metabolism through different pathways, researchers are studying whether targeting both at once could improve weight-loss results.

So far, the most research involves a combination of cagrilintide and semaglutide, known as CagriSema. Cagrilintide targets amylin receptors, while semaglutide targets GLP-1 receptors. The FDA is expected to approve CagriSema in late 2026.

In clinical studies, after 68 weeks of treatment with CagriSema, people living with overweight or obesity lost around 20% of their starting body weight. For people also living with Type 2 diabetes, the average was a bit lower. These participants lost about 14% of starting body weight.

These studies also showed that the combination treatment worked significantly better than cagrilintide or semaglutide used alone. This shows the potential of future combination treatments for weight management.

6. GLP-1 and amylin seem to have similar side effects, with one key exception

GLP-1 and amylin both affect the digestive system. So they cause similar side effects, such as:

• Nausea

• Vomiting

• Diarrhea

• Constipation

• Stomach pain

It’s possible that combining GLP-1 and amylin-based treatments may increase the chance of side effects. But researchers don’t have enough information yet to know if that’s the case.

One key area of interest in amylin-based medications has to do with maintaining muscle mass. There is some concern around the amount of muscle loss that can occur when taking GLP-1 medications. This is one reason why protein intake and strength training are so important when taking one of these medications.

Amylin helps preserve muscle mass by shifting the body’s focus to burning fat. So researchers are interested in how amylin-based medications may help prevent the muscle loss seen with GLP-1 medications. But there isn’t enough clinical information available yet to know whether or not this is true.

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Written by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Sheila McAdoo, PharmD

Sheila McAdoo, PharmD, is a licensed pharmacist in Virginia and New York. She has worked in the pharmacy industry for 14 years.

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