CagriSema and amylin: what's next after GLP-1s

CagriSema pairs semaglutide with an amylin analog. Here is what the REDEFINE trials found, where the FDA review stands, and how amylin differs from GLP-1.

For the past few years, weight-loss drug news has mostly been GLP-1 news. Semaglutide and tirzepatide changed what doctors expect from a medicine for obesity. The next wave is built around a different hormone: amylin. CagriSema, from Novo Nordisk, is the first amylin-based combination to reach an FDA decision for weight management.

This post covers what amylin does, what the main trials showed, and where the regulatory process stands as of early October 2026.

What amylin is

Amylin is a hormone made by the same pancreatic cells that make insulin, and it is released alongside insulin after you eat. It has three main jobs. It slows how fast food leaves the stomach, it holds back glucagon (a hormone that raises blood sugar) after meals, and it signals to the brain that a meal is finished.

Natural amylin is hard to use as a drug. It breaks down within minutes and tends to clump in solution. The one amylin drug already approved in the US, pramlintide (Symlin), is used in diabetes and has to be injected before meals several times a day.

Cagrilintide is a reworked amylin designed to last about a week. It acts on both amylin receptors and calcitonin receptors, which places it in a group researchers call DACRAs (dual amylin and calcitonin receptor agonists).

How amylin differs from GLP-1

GLP-1 is a gut hormone. Drugs such as semaglutide mimic it to boost insulin release when blood sugar is high, slow the stomach and reduce appetite. Amylin analogs overlap on fullness and stomach emptying, but they act through a separate set of receptors in the brain. They do not directly increase insulin.

Because the two hormones use different pathways, the theory is that combining them adds up to more than either one alone. That theory is what the REDEFINE trials set out to test.

What cagrilintide does on its own

In a phase 2 trial published in The Lancet in 2021, once-weekly cagrilintide alone produced weight loss of 6.0% to 10.8% over 26 weeks depending on dose, compared with 3.0% on placebo. The highest dose did slightly better than liraglutide 3.0 mg, an older GLP-1 drug, in the same study.

That is meaningful but modest next to today's GLP-1 drugs. Cagrilintide alone is not approved anywhere.

The REDEFINE results

REDEFINE 1 enrolled 3,417 adults with obesity (or overweight plus a related health problem) who did not have type 2 diabetes. Over 68 weeks, average weight loss was:

CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg, weekly): 20.4%
Semaglutide alone: 14.9%
Cagrilintide alone: 11.5%
Placebo: 3.0%

When researchers looked only at people who stayed on treatment, the CagriSema figure rose to 22.7%. Different summaries quote different numbers for the same trial, so it helps to check which kind of analysis a figure comes from.

REDEFINE 2 studied 1,206 adults with obesity and type 2 diabetes. Weight loss at 68 weeks was 13.7% with CagriSema versus 3.4% with placebo, and 74% of people on CagriSema reached an HbA1c (a measure of long-term blood sugar) of 6.5% or lower, compared with 15.9% on placebo. Both trials were published in the New England Journal of Medicine in 2025.

Side effects were mostly digestive. In REDEFINE 1, about 80% of people on CagriSema reported gastrointestinal effects such as nausea, vomiting, diarrhea or constipation, against about 40% on placebo. Most were mild to moderate and eased over time.

The head-to-head miss

REDEFINE 4 compared CagriSema directly with tirzepatide 15 mg over 84 weeks in 809 people. CagriSema did not meet its main goal of showing it was not worse than tirzepatide. Under the main analysis, weight loss was 20.2% with CagriSema and 23.6% with tirzepatide. Among people who stayed on treatment, the figures were 23.0% and 25.5%.

So CagriSema works well, but on current evidence it does not beat the strongest drug already on the market.

The FDA filing and timing

Novo Nordisk submitted CagriSema to the FDA for weight management in December 2025, based on REDEFINE 1 and 2. The company has said it expects a decision in late 2026, and its guidance points to the fourth quarter. A standard review for a new medicine takes roughly 10 to 12 months from filing, which fits that window.

At the time of writing, we had not seen a public decision. If approved, CagriSema would be a fixed-dose combination product in a single injection, not two separate drugs.

Other amylin drugs in the pipeline

CagriSema is not the only amylin project. Novo Nordisk is moving amycretin, a single molecule that acts on both GLP-1 and amylin receptors, into phase 3. Eli Lilly's eloralintide and petrelintide, from Zealand Pharma and Roche, are amylin-type drugs that have finished phase 2 and are heading into larger trials. None of these is approved.

A note on research vials

Cagrilintide is sold online as a "research peptide." Those vials are not CagriSema. They are not made or tested to drug standards, and no trial has studied them. The trials used a specific co-formulated product with a slow dose increase over about 16 weeks.

The bottom line

Amylin analogs are a real, distinct class, not a rebranded GLP-1. Adding cagrilintide to semaglutide gave more weight loss than semaglutide alone in large trials, though it fell short of tirzepatide head to head. An FDA decision is expected before the end of 2026.

You can compare the individual compounds on their pages: cagrilintide, semaglutide and tirzepatide.

This is educational information, not medical advice.