Amylin and amylin analogs explained

Amylin is a hormone made in the pancreas and released together with insulin [1]. This guide explains what amylin does, how the approved amylin drug pramlintide works, why longer-acting analogs and dual amylin and calcitonin receptor agonists are being developed, how they differ from GLP-1 receptor agonists, what the trials so far show, and which safety questions remain open. It describes research; it does not recommend any product or use.

What amylin is

Amylin is stored with insulin in the secretory granules of pancreatic beta cells and released with it in response to food intake [1]. In nonclinical studies, amylin slows gastric emptying without changing overall nutrient absorption, suppresses glucagon secretion, and reduces food intake through centrally mediated effects on appetite [1]. A review of the feeding literature describes amylin's best-studied effect as controlling meal size by producing satiation, with the caudal hindbrain, and the area postrema in particular, as a key site of action [4].

Amylin acts through receptors built from the calcitonin receptor paired with one of three receptor activity-modifying proteins (RAMPs), giving the AMY1, AMY2 and AMY3 receptors [3]. The calcitonin receptor can also signal on its own, which is why some drugs in this class are described by how strongly they activate each receptor type [3, 6].

Pramlintide: the first amylin drug

Native amylin has a strong tendency to form amyloid fibrils, which makes it a difficult starting point for a medicine [5]. Pramlintide is a synthetic 37-amino-acid analog that differs from human amylin by proline substitutions at positions 25, 28 and 29 [1]. FDA approved it as Symlin in March 2005 under NDA 021332 [2]. Its label describes it as an adjunct for people with type 1 or type 2 diabetes who use mealtime insulin and have not reached glucose goals despite optimal insulin therapy [1]. The label carries a boxed warning that use with insulin increases the risk of severe hypoglycemia, particularly in type 1 diabetes [1]. Pramlintide's half-life in healthy individuals is approximately 48 minutes [1], and developers of newer analogs note that it requires several injections a day [5]. As of 22 October 2026, the Symlin products listed under NDA 021332 in Drugs@FDA carried a marketing status of discontinued [2].

Why long-acting analogs are being studied

The short half-life of pramlintide is one reason developers have engineered amylin analogs that last much longer [5]. Cagrilintide is a stable, lipidated amylin analog developed for once-weekly use [5]. Eloralintide is another fatty-acid-acylated amylin analog, with a reported half-life of 310 to 366 hours across single doses of 0.4 to 12 mg in a phase 1 study [7]. Amycretin goes a step further by joining a GLP-1 receptor agonist portion and an amylin receptor agonist portion in a single molecule [12].

DACRAs and receptor selectivity

A dual amylin and calcitonin receptor agonist, or DACRA, activates both the amylin receptors and the calcitonin receptor [6]. Cagrilintide is a DACRA built on an amylin backbone, while the experimental KBP compounds are DACRAs built on salmon calcitonin [6]. In rat models, the calcitonin-based KBP-336 showed a bias toward the calcitonin receptor and, at its highest dose, a larger body-weight effect than cagrilintide, which the authors took as evidence that receptor balance matters [6]. Eloralintide was designed with the opposite emphasis: in cell assays it activated AMY1R about 12-fold more potently than the calcitonin receptor, and in lean rats it caused less conditioned taste avoidance than cagrilintide [7]. Whether these preclinical differences translate into different outcomes in people has not been tested head to head.

How amylin agents differ from GLP-1 receptor agonists

GLP-1 receptor agonists such as semaglutide act on the GLP-1 receptor, which is present in several brain areas involved in appetite regulation [8]. Amylin analogs act on a different receptor family, the calcitonin receptor and its RAMP complexes [3]. Because the two hormones work through separate receptors, developers have combined them, either as two co-administered molecules such as CagriSema or as a single dual-acting molecule such as amycretin [10, 12]. Their side-effect profiles also appear to differ in at least one respect: the semaglutide label describes increases in resting heart rate [8], whereas a 12-week phase 1 study of eloralintide reported mean pulse-rate decreases from baseline [13].

The evidence so far

Most human data on newer amylin agents come from randomized trials funded by their developers [9, 10, 11, 12]. In a 26-week phase 2 trial, cagrilintide alone reduced mean body weight by 6.0% to 10.8% across doses versus 3.0% with placebo [9]. In the 68-week REDEFINE 1 phase 3 trial of 3417 adults without diabetes, cagrilintide combined with semaglutide produced an estimated mean body-weight change of -20.4% versus -3.0% with placebo [10]. In REDEFINE 2, among 1206 adults with type 2 diabetes, the corresponding figures were -13.7% and -3.4% [16]. In a 48-week phase 2 trial of eloralintide, mean body-weight change ranged from -9% to -20% across dose groups versus -0.4% with placebo [11]. In an early-phase study of subcutaneous amycretin, the highest-dose group showed an estimated mean change of -24.3% at 36 weeks versus -1.1% with placebo, although many participants withdrew [12]. A 36-week phase 2 trial in type 2 diabetes found that amycretin, now also called zenagamtide, lowered HbA1c more than placebo at every dose tested [15].

Open safety questions

Gastrointestinal adverse events are the most frequently reported problem: in REDEFINE 1 they affected 79.6% of participants on the combination versus 39.9% on placebo, and were mainly transient and mild to moderate [10]. Pramlintide carries a boxed warning for severe hypoglycemia when used with insulin, which makes the behaviour of newer amylin agents alongside insulin a relevant question [1]. Cardiovascular outcomes are not yet known; REDEFINE 3, which randomized 7076 adults with established cardiovascular disease, was designed to test the cardiovascular safety and efficacy of CagriSema [14]. The eloralintide and amycretin trials published so far are relatively small and short [11, 12, 13], and the clinical meaning of the heart-rate changes seen with eloralintide has not been established [11, 13]. Long-term data after treatment stops were not available in the sources reviewed.

Key points

• Amylin is co-secreted with insulin and acts through calcitonin receptor and RAMP complexes [1, 3].
• Pramlintide (Symlin) is an FDA-approved amylin analog; its Drugs@FDA products were listed as discontinued as of 22 October 2026 [1, 2].
• Long-acting analogs (cagrilintide, eloralintide) and a dual GLP-1/amylin molecule (amycretin) are investigational [5, 7, 12]; CagriSema (cagrilintide/semaglutide) was not FDA-approved as of 22 October 2026, and Drugs@FDA, which lists approved applications only, returned no record for cagrilintide [17].
• DACRAs activate both amylin and calcitonin receptors; eloralintide is designed to favour AMY1R [6, 7].
• Gastrointestinal events are common, and cardiovascular outcome data are pending [10, 14].