Pramlintide
The only amylin drug ever approved, a mealtime partner to insulin, now off the US market
Pramlintide copies amylin, the hormone beta cells release alongside insulin, which people with diabetes make too little of. Approved in 2005 as Symlin for mealtime use with insulin, it lowered glucose and weight modestly at the price of nausea and a boxed hypoglycaemia warning. Every US product has since been discontinued.
What is it?
Amylin is stored and released with insulin by the pancreas's beta cells, and in both type 1 and type 2 diabetes less of each is released after meals. The label describes amylin slowing gastric emptying, and in the studies pramlintide blunted the rise of glucagon and glucose after eating. Tracer work in type 1 diabetes showed where the effect comes from: meal glucose enters the blood more slowly and glucagon is suppressed, while the liver's own glucose output does not change. Liraglutide, tested the same way, did not suppress glucagon.
It was never a stand-alone drug. The label calls for cutting mealtime insulin by half when it is started, then 15 mcg before major meals in type 1 diabetes, rising to 30 or 60 mcg, or 60 mcg rising to 120 mcg in type 2, with at least three days between steps to limit nausea. Its boxed warning is severe hypoglycaemia, most of all in type 1 diabetes, usually within three hours of an injection.
The results were modest and real: in a year-long trial, HbA1c fell by about 1% at three months but only 0.6% at a year, with weight loss. In type 2 diabetes on basal insulin, adding it at meals lowered HbA1c about as much as adding mealtime insulin, without the 4.7 kg weight gain the insulin caused, at the cost of nausea in one in five.
Weight was always the other story. In people with obesity but no diabetes, it alone took off a few percent over 24 weeks, and about 11% when combined with sibutramine or phentermine. Its successors pursue the same idea: a pramlintide-insulin co-formulation lowered weight by about 2 kg in type 1 diabetes, and dual-hormone artificial pancreas systems deliver it alongside insulin.
Drugs@FDA now lists every Symlin product as discontinued, and the newer amylin drugs in development, such as cagrilintide, are built to last far longer than pramlintide's 48 minutes. It also has an unexpected property: given to people with migraine, it triggered migraine-like attacks.
Mechanism of Action
Pramlintide is a stabilised copy of amylin, the hormone beta cells release with insulin; it slows meal glucose and suppresses glucagon.
Slower gastric emptying
Slows how fast food leaves the stomach, delaying meal glucose (label 12.1; 2.6- to 3.8-fold delay in adolescents).
Glucagon suppression
Blunts the post-meal glucagon rise in type 1 diabetes, which liraglutide did not (2018 study).
Short-acting
Half-life about 48 minutes, so it is injected before each major meal (label 12.3).
Published Research
These are the studies in people, read from their PubMed abstracts, with dosing from the Symlin label read October 1, 2026.
A year in type 2 diabetes
In 538 insulin-treated people randomised to three doses or placebo for 52 weeks, HbA1c fell by 0.9% and 1.0% at week 13 on the two higher doses and by 0.6% at week 52 on the highest, without more insulin or severe hypoglycaemia. Weight fell on every dose, and nausea was the commonest adverse event, easing early.
What it does at a meal
In a four-week crossover study in 14 men with type 1 diabetes, pramlintide lowered mean daytime glucose (8.3 against 10.2 mmol/L) and the glucose and glucagon rises after meals, with insulin levels unchanged. A small study of the mechanism.
In an artificial pancreas
In a randomised crossover trial in adults with type 1 diabetes, a system delivering rapid insulin with pramlintide raised time in the target glucose range from 74% to 84%, mostly in the daytime; a version pairing it with regular insulin did not help (69%).
A migraine trigger
In 36 people with migraine, an infusion of pramlintide caused headache in 88% and migraine-like attacks in 41%, close to the 97% and 56% caused by CGRP, its relative; receptor studies pointed to the amylin receptor.
No help after gastric bypass
In an eight-week open-label study of hypoglycaemia after gastric bypass, 14 of 20 participants finished; meal-test glucose, glucagon and insulin did not change, and neither did the frequency of low glucose readings.
Against mealtime insulin in type 2
In 113 people with type 2 diabetes on basal insulin, adding 120 µg pramlintide at meals or a rapid-acting insulin gave similar HbA1c falls (1.1% against 1.3%), but insulin added 4.7 kg while pramlintide added none, and more reached HbA1c 7% or less without weight gain or severe hypoglycaemia (30% against 11%). Nausea affected 21% on pramlintide.
Glucagon after meals in type 1
In type 1 diabetes, pramlintide cut the meal-stimulated glucagon rise (incremental area 1,988 to 737 pg/mL/min) and the glucose rise, while liraglutide changed neither.
Where the glucose goes
In a tracer study in type 1 diabetes, pramlintide lowered the post-meal glucose rise by slowing the appearance of meal glucose and suppressing glucagon; the liver's own glucose output and insulin sensitivity did not change.
Adolescents with type 1 diabetes
In 9 adolescents, 15 and 30 µg doses lowered post-meal glucagon and glucose against placebo and delayed gastric emptying 2.6- to 3.8-fold, with no treatment-related adverse events.
Combined with weight-loss drugs
In 244 adults with obesity but no diabetes, 24 weeks of pramlintide 120 µg three times daily lost 3.7% of body weight against 2.2% on placebo; combined with sibutramine or phentermine, losses were about 11%, with small rises in heart rate and blood pressure.
A co-formulation with insulin
In type 1 diabetes, ADO09, pramlintide co-formulated with an insulin analogue for mealtimes, lowered weight by 2.1 kg against insulin lispro with 21% less mealtime insulin and no clear difference in hypoglycaemia; gastrointestinal symptoms were more common. It is investigational.
Dosing Data
Symlin was injected under the skin before major meals, separately from insulin, with mealtime insulin cut by half at the start.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the Symlin label (SPL version 18, effective December 18, 2019) and the studies.
Contraindications & Cautions
From the label.
Legal Status
Approved, and no longer marketed in the US.
Frequently Asked Questions
?Can you still get pramlintide?
Not as Symlin in the US: Drugs@FDA lists every Symlin product as discontinued, although the approval itself stands.
?Why was it taken with insulin?
It replaces amylin, which the pancreas releases with insulin; the label requires cutting mealtime insulin by half at the start because the combination can cause severe hypoglycaemia.
?How does it relate to cagrilintide?
Both copy amylin. Pramlintide lasts about 48 minutes and was injected at every meal; cagrilintide, in development, is designed for weekly dosing.
?Did it cause weight gain like insulin?
No. Added at meals in type 2 diabetes on basal insulin, it did not change weight, while adding mealtime insulin added 4.7 kg.
?Can it be used for weight loss?
It was tested: alone it took off a few percent of body weight over 24 weeks, and about 11% with sibutramine or phentermine. It was never approved for obesity.
References
- [fda-pi] Symlin (pramlintide acetate) prescribing information, boxed warning and sections 1, 2, 4, 5, 6, 12.1 and 12.3 (DailyMed SPL version 18, effective December 18, 2019; read October 1, 2026).
- [pubmed] Ratner RE, et al. "Adjunctive therapy with the amylin analogue pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with type 2 diabetes." Diabetes Technol Ther, 2002;4(1):51-61. PMID: 12017421.
- [pubmed] Nyholm B, et al. "The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus." Metabolism, 1999;48(7):935-41. PMID: 10421239.
- [pubmed] Haidar A, et al. "A Novel Dual-Hormone Insulin-and-Pramlintide Artificial Pancreas for Type 1 Diabetes: A Randomized Controlled Crossover Trial." Diabetes Care, 2020;43(3):597-606. PMID: 31974099.
- [pubmed] Ghanizada H, et al. "Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients." Ann Neurol, 2021;89(6):1157-1171. PMID: 33772845.
- [pubmed] Sheehan A, et al. "Pramlintide for post-bariatric hypoglycaemia." Diabetes Obes Metab, 2022;24(6):1021-1028. PMID: 35137513.
- [clinical-trial] Riddle M, et al. "Randomized comparison of pramlintide or mealtime insulin added to basal insulin treatment for patients with type 2 diabetes." Diabetes Care, 2009;32(9):1577-82. PMID: 19502544.
- [pubmed] Galderisi A, et al. "Pramlintide but Not Liraglutide Suppresses Meal-Stimulated Glucagon Responses in Type 1 Diabetes." J Clin Endocrinol Metab, 2018;103(3):1088-1094. PMID: 29211871.
- [pubmed] Hinshaw L, et al. "Effect of Pramlintide on Postprandial Glucose Fluxes in Type 1 Diabetes." J Clin Endocrinol Metab, 2016;101(5):1954-62. PMID: 26930181.
- [pubmed] Chase HP, et al. "Pramlintide lowered glucose excursions and was well-tolerated in adolescents with type 1 diabetes: results from a randomized, single-blind, placebo-controlled, crossover study." J Pediatr, 2009;155(3):369-73. PMID: 19464026.
- [clinical-trial] Aronne LJ, et al. "Enhanced weight loss following coadministration of pramlintide with sibutramine or phentermine in a multicenter trial." Obesity (Silver Spring), 2010;18(9):1739-46. PMID: 20094043.
- [clinical-trial] Andersen G, et al. "ADO09, a co-formulation of pramlintide and insulin A21G, lowers body weight versus insulin lispro in type 1 diabetes." Diabetes Obes Metab, 2024;26(10):4639-4645. PMID: 39109464.
Sources & Citations
Studies were read from their PubMed abstracts; the Symlin label (SPL version 18, effective December 18, 2019) was read October 1, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.