Amylin analogs: pramlintide, cagrilintide and the amylin drugs in development

Amylin is a 37-amino-acid hormone made by the same pancreatic beta cells that make insulin, and released with it in response to meals ^[5]. Its effects are three: it slows gastric emptying, it suppresses glucagon after meals, and it promotes meal termination through the brain ^[1]. People with diabetes are deficient in it, which is the original case for replacing it ^[6].

Amylin acts on receptors built from the calcitonin receptor paired with an accessory protein; the heterodimer structure of these amylin-calcitonin receptor complexes is what guided the design of the newer, long-acting drugs ^[7]. Human amylin itself clumps into aggregates, which is why it was never used as a drug: pramlintide was designed from the non-aggregating rat form ^[7].

The three names searchers use overlap almost completely. An amylin analog is a modified version of the hormone; an amylin mimetic is any drug that copies its effects; an amylin receptor agonist is any drug that switches on its receptors, which includes non-peptide molecules still in preclinical work ^[7]. Some newer drugs also hit the calcitonin receptor (cagrilintide) or the GLP-1 receptor (amycretin), so the class boundaries are looser than the names suggest.

According to its prescribing information, pramlintide acts as an amylin analogue to slow gastric emptying, reduce the rise in glucagon after meals, and modulate satiety so that people eat fewer calories ^[2]. The combined effect is on blood sugar after meals, not fasting blood sugar: a review of its trials reported 2-hour post-meal glucose lower by 3.4 to 5 mmol/L, HbA1c lower by 0.2 to 0.7 points, and no effect on fasting glucose ^[5].

The trial evidence, pooled:

• Type 2 diabetes and obesity. A meta-analysis of eight trials found pramlintide lowered HbA1c by 0.33 points and weight by 2.57 kg. All the diabetes trials were in people on insulin; the obesity trials used 120 to 360 mcg per dose two or three times a day. Nausea increased; hypoglycaemia did not in that analysis ^[8].
• Type 1 diabetes. Ten placebo-controlled trials (1,978 people on pramlintide) found lower HbA1c, lower mealtime insulin doses and lower weight, at the cost of more nausea and transient hypoglycaemia ^[9].

Pramlintide proved that adding amylin back works, but the effect was modest and the schedule demanding: injections before each major meal ^[2][1]. Those two limits are what the second generation was built to fix.

The label figures above are what the US prescribing information states ^[2]. The boxed warning is the defining feature: because pramlintide lowers post-meal glucose on top of insulin, the risk of severe hypoglycaemia rises, particularly in type 1 diabetes, and the label pairs the first dose with a cut in mealtime insulin. Pramlintide is not approved for weight loss, even though weight fell in its trials ^[8].

Cagrilintide is a once-weekly analogue that activates both amylin and calcitonin receptors, which places it among the dual amylin and calcitonin receptor agonists ^[7]. It was co-formulated with semaglutide into one weekly injection, CagriSema, and in trials the combination did better than either part alone ^[7].

In REDEFINE 1, over 68 weeks and with everyone assumed to stay on treatment, weight fell 11.8% on cagrilintide 2.4 mg alone, 16.1% on semaglutide 2.4 mg alone and 22.7% on the combination, against 2.3% on placebo ^[10]. Novo Nordisk filed CagriSema with the FDA in December 2025 ^[3] and moved cagrilintide alone into its own phase 3 programme, RENEW ^[11]. Trial doses are on cagrilintide dosage and the combination's trials on the CagriSema record; side effects across the trials are on cagrilintide side effects.

Eloralintide (Lilly) is a selective amylin receptor agonist. In a 48-week phase 2 trial of 263 adults, weight fell 9% at 1 mg up to 20% at 9 mg, against 0.4% on placebo; nausea and fatigue were the most common adverse events ^[12]. Lilly has also combined it with tirzepatide: in a phase 2 trial in 367 adults with type 2 diabetes, the top combination reached 23.3% weight loss at 48 weeks against 14.8% on tirzepatide 15 mg alone ^[14]. More on eloralintide.

Petrelintide (Zealand Pharma and Roche) is an analogue of human amylin. In ZUPREME 1, 493 adults were randomised; at 28 weeks weight fell 7.9% to 9.8% across doses against 1.7% on placebo, and nausea affected 20% against 6% on placebo, with vomiting in 3% ^[15].

Amycretin (Novo Nordisk) is one molecule that activates both GLP-1 and amylin receptors. In its first multi-dose trial, weight fell 22.0% at 36 weeks on 20 mg and 24.3% on 60 mg ^[16], and Novo planned a phase 3 programme from the first quarter of 2026 ^[17].

One 2026 network meta-analysis compared the long-acting amylin-based drugs indirectly, across six trials and 4,642 adults without diabetes. Against placebo, high-dose subcutaneous amycretin produced the largest weight reduction (-23.95%), followed by high-dose eloralintide (-18.01%) and high-dose CagriSema (-17.18%), all ahead of semaglutide 2.4 mg (-11.45%) ^[4]. The authors rated the data sparse and low-certainty, and gastrointestinal adverse events rose with the high doses ^[4].

Two things are clear from the evidence so far. First, amylin drugs used alone produce roughly 8% to 20% weight loss in trials so far ^[12][15][10], a range that overlaps semaglutide 2.4 mg rather than clearly exceeding it ^[4]. Second, the largest effects come from pairing amylin with GLP-1 activity, whether as two drugs (CagriSema) or as one molecule (amycretin). Nausea is the shared tolerability cost of the class ^[7].