Amylin and GLP-1: two satiety signals behind CagriSema

CagriSema is a once-weekly combination of cagrilintide, an amylin analog, and semaglutide, a GLP-1 receptor agonist. The two hormones act on different receptors, and both slow the stomach, but their appetite effects are not interchangeable. This article sets out what amylin does, what the phase 3 REDEFINE trials report for the combination, and where that evidence stops.

What does amylin do?

Amylin is a pancreatic hormone, co-secreted with insulin from beta cells. Alhazmi and le Roux's 2026 narrative review describes three actions: it slows gastric emptying, suppresses glucagon secretion, and promotes meal termination through central mechanisms. Pramlintide, the first approved amylin analog, showed the pathway could be used therapeutically, but its weight effect was modest and it required frequent dosing. Cagrilintide is one of the long-acting agents the review covers.

The gastric effect overlaps with GLP-1. Our gastric emptying article reports a pooled delay of about 74 minutes for GLP-1 receptor agonists, although that estimate is rated very low certainty. The appetite question is separate. In a 16-week liraglutide trial, gastric emptying accounted for only 4% to 6% of the variance in appetite measures. The sources we opened do not establish how much of amylin's appetite effect runs through the stomach, so the two pathways should not be treated as the same mechanism with different names.

What did REDEFINE 2 show in type 2 diabetes?

REDEFINE 2 is the most direct trial result we found. Davies and colleagues randomized 1,206 adults with obesity and type 2 diabetes, in a 3:1 ratio, to once-weekly CagriSema or to placebo, both with lifestyle intervention. The trial was double-blind, ran in 12 countries for 68 weeks, and was funded by Novo Nordisk (NCT05394519).

The estimated difference in weight change was -10.4 percentage points (95% CI, -11.2 to -9.5), and the authors report most gastrointestinal events as transient and mild or moderate. Still, more than twice the proportion of CagriSema participants reported gastrointestinal events compared with placebo. Entry required a BMI of 27 or more and an HbA1c between 7% and 10%, so the trial does not describe people with better-controlled diabetes or with obesity alone. The glycemic outcomes in the table should not be read as a general picture of obesity care, and the REDEFINE 1 results in the next section come from a different population.

What do the REDEFINE 1 sub-analyses add?

REDEFINE 1 enrolled adults without diabetes and has produced several secondary and post hoc analyses. Busetto and colleagues asked how many participants reached an anthropometric target at week 68, defined as a BMI below 27 kg/m² and a waist-to-height ratio below 0.53. The results were as follows.

For the headline number, we rely on the sponsor. Novo Nordisk's December 2025 announcement reports a 22.7% weight loss at 68 weeks with CagriSema against 2.3% with placebo in REDEFINE 1, a figure it describes as the effect if all participants stayed on treatment. It also reports adverse-event discontinuation of 5.9% on CagriSema and 3.5% on placebo. That is a different way of counting from REDEFINE 2's 13.7%, which includes people who stopped treatment, and the two trials enrolled different populations, so the figures cannot be set side by side.

A separate analysis by Verma and colleagues in Hypertension reported blood pressure. Systolic pressure fell by 10.9 mm Hg on CagriSema and 2.8 mm Hg on placebo, and diastolic pressure by 5.4 and 1.7 mm Hg. The share of participants reaching blood pressure targets was 63.0% on CagriSema and 32.0% on placebo. The authors also looked at 167 participants with resistant hypertension at baseline, where the figures were 42.0% and 29.3%. The odds ratio of 1.7 has a confidence interval of 0.7 to 4.4, which includes 1, so that subgroup difference is not statistically clear.

Where the evidence is thin

• The primary REDEFINE 1 publication was not opened in this review. Most REDEFINE 1 figures above come from secondary or post hoc analyses, and the headline weight figure comes from the sponsor's announcement rather than a peer-reviewed abstract.
• REDEFINE 2 was funded by Novo Nordisk, according to its abstract. Readers should weigh the efficacy numbers with that in mind and check the trial registration for the full protocol.
• The trials ran for 68 weeks. The abstracts we opened say nothing about durability beyond that point or about longer-term safety.
• Gastrointestinal events were common, and the abstracts give no breakdown of which events drove discontinuations.

Regulatory status and research-grade material

On December 18, 2025, Novo Nordisk announced that it had submitted a New Drug Application to the FDA for once-weekly CagriSema. None of the sources we opened, checked on October 7, 2026, reports an approval, so we treat CagriSema as under review, and we did not look for the status of cagrilintide on its own. Check the sponsor's announcements and the FDA's website for the current position. Semaglutide is different: approved prescription products containing it exist. Research-grade material is not an approved product. Anyone seeking treatment for obesity should talk to a physician, who can weigh the gastrointestinal and blood pressure data against an individual's history.

Bottom line

CagriSema combines cagrilintide with semaglutide. In REDEFINE 2, the combination lowered mean body weight by 13.7% against 3.4% on placebo over 68 weeks in people with type 2 diabetes, with gastrointestinal events far more frequent. Amylin and GLP-1 both slow gastric emptying, and whether that slowing drives appetite remains open for both. For the GLP-1 side of the question, read why GLP-1 drugs slow gastric emptying.