Cagrilintide: Long-Acting Amylin Analog Research Guide

TL;DR

Cagrilintide is a long-acting amylin analog studied for weight management with once-weekly dosing. In a phase 2 dose-finding trial, mean weight loss ranged from about 6.0% at the lowest dose to about 10.8% at the highest dose over 26 weeks, versus about 3.0% for placebo (Lau et al., 2021). Its reported elimination half-life is about 180 hours (159 to 195 hours), which is why the trial used a weekly schedule (Kruse et al., 2021). The most commonly reported side effects were gastrointestinal, nausea most frequent, and most events were mild to moderate (Lau et al., 2021).

- Cagrilintide is a long-acting amylin analog studied for weight management and given once weekly in the trial data verified here (Lau et al., 2021). - In a phase 2 dose-finding trial, mean weight loss ranged from about 6.0% at the lowest dose to about 10.8% at the highest dose over 26 weeks, versus about 3.0% for placebo (Lau et al., 2021). - Its reported elimination half-life is about 180 hours (159 to 195 hours), which is why the trial used once-weekly dosing (Kruse et al., 2021). - The most commonly reported side effects were gastrointestinal, with nausea most frequent and most events described as mild to moderate (Lau et al., 2021). - CagriSema is the investigational combination of cagrilintide plus semaglutide; this hub reports only verified monotherapy data, and for context semaglutide alone produced about 15% mean loss in STEP 1 (Wilding et al., 2021).

What is cagrilintide?

Cagrilintide is a long-acting, acylated amylin analog that has been studied for weight management with once-weekly dosing (Lau et al., 2021; Kruse et al., 2021).

Amylin is a hormone the body releases after eating. It works alongside insulin to signal fullness. Natural amylin breaks down in minutes, so it cannot be dosed on a weekly schedule. Cagrilintide is engineered to copy amylin's signal while staying active far longer. The chemistry paper that described its development attached a C20 fatty diacid to the peptide so it binds reversibly to albumin, which is the design feature behind its long duration (Kruse et al., 2021). In the phase 2 trial cited here, it was given as a once-weekly subcutaneous injection (Lau et al., 2021). Human evidence for cagrilintide as a single agent is limited to this phase 2 stage in the citations verified for this page.

How does cagrilintide work in the body?

Cagrilintide mimics amylin, activating amylin receptors that reduce appetite and slow how fast the stomach empties (Lau et al., 2021; Kruse et al., 2021).

The practical effect studied in trials is reduced food intake and greater feelings of fullness after meals. This is a different pathway from the GLP-1 drugs that dominate the current weight-loss field. GLP-1 receptor agonists such as semaglutide act on the incretin system (Wilding et al., 2021), while amylin analogs like cagrilintide act on the amylin system. Because the pathways differ, researchers have paired them to see if the two signals add up, which is the logic behind the CagriSema combination described below.

What did the phase 2 cagrilintide trial report?

In the phase 2 dose-finding trial, mean weight loss across cagrilintide doses ran from about 6.0% to 10.8% at 26 weeks, compared with about 3.0% for placebo and about 9.0% for the liraglutide 3.0 mg comparator (Lau et al., 2021).

The trial tested several once-weekly doses against placebo and against liraglutide, a daily GLP-1 drug used as an active comparator. The highest cagrilintide dose produced greater mean loss than liraglutide 3.0 mg in that study (Lau et al., 2021).

Values from Lau et al., 2021 (The Lancet, PMID 34798060).

What doses of cagrilintide were used in research?

The ranges below reflect what published studies and commonly studied research protocols report. This is educational, not a prescription or a personal recommendation. In the phase 2 study, participants received once-weekly cagrilintide at 0.3, 0.6, 1.2, 2.4, or 4.5 mg (Lau et al., 2021).

These numbers describe a controlled trial, not a personal plan. This page does not tell anyone what to take, when, or how to inject. Any decision about a metabolic protocol belongs with a qualified clinician who knows the person's full history.

What is cagrilintide's half-life and dosing schedule?

Cagrilintide has a reported elimination half-life of about 180 hours, in the range of 159 to 195 hours, which supports the once-weekly schedule used in the trial (Kruse et al., 2021).

Natural amylin clears from the body in minutes. The chemistry team measured cagrilintide's long half-life as roughly 7 to 8 days, which is the design feature that makes weekly dosing possible instead of dosing several times a day (Kruse et al., 2021). By contrast, the earlier amylin drug pramlintide has a half-life measured in minutes and is dosed at each meal.

What is CagriSema?

CagriSema is the investigational combination of cagrilintide plus semaglutide, pairing an amylin analog with a GLP-1 receptor agonist.

The rationale is to combine two appetite pathways in one regimen. This hub reports only what the verified citations cover. For cagrilintide, that is the phase 2 monotherapy data (Lau et al., 2021). For semaglutide, the STEP 1 trial reported about 15% mean weight loss over 68 weeks (Wilding et al., 2021). Published outcomes for the specific fixed combination sit outside the citations verified for this page, so no combination percentage is stated here.

What are the reported side effects of cagrilintide?

The most commonly reported side effects were gastrointestinal, with nausea most frequent and most events described as mild to moderate (Lau et al., 2021).

Gastrointestinal effects are a familiar pattern across amylin and incretin appetite drugs, and in the cagrilintide trial they tended to track with dose (Lau et al., 2021). The verified data here covers 26 weeks, so longer-term tolerability for cagrilintide as a single agent is not established by these citations.

How does cagrilintide compare with GLP-1 and dual or triple agonists?

Cagrilintide acts through amylin, a different pathway than the incretin drugs, so its monotherapy loss of about 6 to 10.8% sits below the leading GLP-1 class agents measured in their own trials (Lau et al., 2021; Wilding et al., 2021; Jastreboff et al., 2022; Jastreboff et al., 2023).

These figures come from separate trials with different designs, durations, and participants, so they are not direct comparisons. Among these agents, the one true head-to-head study was SURPASS-2, which compared tirzepatide with semaglutide (Frias et al., 2021). For a deeper class breakdown, see the retatrutide vs tirzepatide comparison linked below.

Does weight come back after stopping this class of therapy?

Long-term withdrawal data specific to cagrilintide is limited, but across this class trials report meaningful weight regain after treatment stops (Wilding et al., 2022; Aronne et al., 2024).

In the STEP 1 extension, participants regained about two-thirds of their lost weight one year after stopping semaglutide (Wilding et al., 2022). SURMOUNT-4 showed a similar pattern after withdrawing tirzepatide (Aronne et al., 2024). One reason the body defends lost weight is adaptive thermogenesis, a drop in energy use that follows weight reduction (Rosenbaum and Leibel, 2010). The practical takeaway from the published record is that these therapies are studied as ongoing regimens, not short courses.