Pramlintide

Origin and structure

Amylin, also called islet amyloid polypeptide, is a hormone of 37 amino acids that the insulin-producing beta cells of the pancreas release together with insulin when food is eaten. In type 1 and type 2 diabetes both hormones are released in smaller amounts. Human amylin is a difficult starting point for a medicine because it readily clumps into amyloid fibrils, the deposits found in the pancreatic islets in type 2 diabetes. A 1990 laboratory study traced that tendency to positions 20 to 29 of the molecule and found that the matching segment of rodent amylin, which carries a proline at position 28, does not form fibrils.

Pramlintide, developed by Amylin Pharmaceuticals, builds on that finding. It is human amylin in which the amino acids at positions 25, 28 and 29 (alanine, serine and serine) are replaced by proline, the residue rat amylin has at all three places. The US label describes the result as a water-soluble peptide with the formula C171H267N51O53S2 and a molecular weight of 3949. After an injection under the skin 30 to 40% reaches the bloodstream, and its half-life in healthy people is about 48 minutes. Its main breakdown product, which lacks the first amino acid, is still active in laboratory tests.

Amylin Pharmaceuticals, which with Eli Lilly also developed exenatide (Byetta), won US approval for both drugs in 2005, six weeks apart. Both later passed to AstraZeneca, which has since given them up: at its request the FDA withdrew the exenatide approvals in 2025, and in the same year it stopped making Symlin. Unlike the newer amylin drugs, pramlintide carries no fatty-acid chain or other half-life extension, which is why each injection covers a single meal.

How it works

Pramlintide copies three effects of amylin that the label reports from studies in people. It slows the emptying of the stomach, so glucose from a meal reaches the blood more gradually. It blunts the rise of glucagon after a meal, a hormone that makes the liver release glucose and whose excess insulin alone does not correct. And it acts on appetite through the brain: in a buffet test, a single injection an hour before the meal cut calorie intake by about 21% in type 1 and 23% in type 2 diabetes compared with placebo.

On its own pramlintide does not cause low blood sugar, according to the label. The risk comes from its combination with mealtime insulin: severe hypoglycaemia, when it happens, usually starts within two to three hours of an injection, which is why the label lowers the mealtime insulin dose when pramlintide is started. In tests in which blood sugar was deliberately lowered, pramlintide did not weaken the body's hormonal defence against hypoglycaemia, and people still noticed their symptoms at a glucose level as low as 45 mg/dl (2.5 mmol/l).

Because its effect lasts only a few hours, pramlintide was injected before each main meal in the trials, two to four times a day, and always as a separate injection: mixing it with insulin changes how both are absorbed.

Is pramlintide approved?

In the US it was approved in 2005, but AstraZeneca has since stopped making and supplying it. In the EU it was never authorised.

Pramlintide offered as a research chemical is not Symlin. It has no marketing authorisation anywhere, is not made under a medicines licence and may not be used in people. Our shop does not sell pramlintide.

• US: the FDA approved Symlin on 16 March 2005 for people with type 1 or type 2 diabetes who use mealtime insulin and have not reached their glucose targets despite optimal insulin therapy, always alongside insulin and never on its own. It is not approved for children or for weight loss. Pen injectors (SymlinPen 60 and 120) followed in 2007. In October 2025 AstraZeneca, which now holds the approval, discontinued US production and supply of SymlinPen, the only presentation left, and stated that this was not a recall. Drugs@FDA lists every Symlin product as discontinued, and no generic version has been approved.
• EU: Amylin Pharmaceuticals applied for a European marketing authorisation in May 2001. In October 2002, after consulting the European committee for medicinal products (then the CPMP), the company concluded that more data would be needed; because the centralised procedure did not allow new data to be added to a running application, it withdrew the application. No medicine containing pramlintide has been authorised in the EU since.
• Netherlands: pramlintide has never been registered. The CBG's medicines register contains no product with it, and the Farmacotherapeutisch Kompas has no entry for it.
• Sport: pramlintide is not named on the WADA Prohibited List. Class S0 prohibits substances with no current approval for human therapeutic use; the English list gives 'discontinued' drugs as an example, which the Dopingautoriteit's Dutch translation renders as drugs whose development was stopped. Symlin's FDA approval has not been withdrawn, although the product is no longer made, and we found no ruling by WADA or the Dopingautoriteit on pramlintide itself.

What the research shows

The approval rests on five long-term placebo-controlled trials, three in type 1 diabetes and two in type 2 diabetes treated with insulin, plus a dose-titration trial in type 1 diabetes; in all, 2,333 people with type 1 and 1,852 with type 2 diabetes received pramlintide in controlled trials. To isolate pramlintide's effect, insulin doses were kept as stable as possible in the long-term trials. Later studies tested it for obesity and in automated insulin systems. The main results:

• Type 1 diabetes, 52 weeks (Ratner et al., Diabet Med 2004): 651 adults added placebo or pramlintide to their insulin. In the groups injecting before three or four meals a day, HbA1c fell 0.29 and 0.34 percentage points against 0.04 on placebo, three times as many people reached an HbA1c below 7%, and weight fell 0.4 kg against a 0.8 kg gain.
• All three long-term type 1 trials (US label): at 6 months HbA1c was 0.25 to 0.34 percentage points lower than on placebo, and weight fell 0.8 to 1.6 kg while it rose 0.4 to 0.8 kg on placebo.
• Type 1 dose-titration trial (US label): in 295 adults, with a slow dose build-up, mealtime insulin lowered at the start and insulin adjusted as in usual care once the maintenance dose was reached, HbA1c fell equally in both groups (0.47 against 0.49 percentage points over 29 weeks), but weight went down 1.33 kg on pramlintide and up 1.25 kg on placebo.
• Type 2 diabetes on insulin, 52 weeks (Hollander et al., Diabetes Care 2003): 656 adults, with or without a sulfonylurea or metformin. On the highest dose HbA1c fell 0.68 percentage points at 26 weeks and 0.62 at 52 weeks, significantly more than on placebo; 46% against 28% reached an HbA1c below 8%, and weight fell 1.4 kg against a 0.7 kg gain. Across both type 2 trials, the US label puts HbA1c at 6 months 0.30 to 0.34 points lower than on placebo.
• Obesity (Smith et al., Diabetes Care 2008): 411 adults with obesity received one of six pramlintide regimens or placebo, with a structured lifestyle programme, for 4 months; weight fell 3.8 to 6.1 kg against 2.8 kg. In an 8-month single-blind extension the placebo group regained its loss, while the two regimens the authors singled out kept 6.1 and 7.2 kg more off than placebo (5.6% and 6.8% of body weight); only 146 people could be evaluated at 12 months.
• Pramlintide with metreleptin: Amylin and its partner Takeda also developed pramlintide together with metreleptin, a leptin analogue, as a treatment for obesity, but stopped in August 2011. Pramlintide was never approved for weight loss.
• Automated insulin delivery (Haidar et al., Diabetes Care 2020): in a randomised crossover trial in adults with type 1 diabetes, an artificial pancreas that delivered rapid-acting insulin plus pramlintide kept glucose in the target range 84% of the time over 24 hours, against 74% with insulin alone, mainly through better daytime control. Gastrointestinal symptoms followed 6% of meals, against none with insulin alone.

Side effects and warnings

Nausea is the most frequent side effect. In the pooled type 1 trials 48% of people on pramlintide reported nausea against 17% on placebo, together with loss of appetite (17% against 2%) and vomiting (11% against 7%). In the type 2 trials nausea affected 28% against 12%, headache 13% against 7%, loss of appetite 9% against 2% and vomiting 8% against 4%. Nausea was most common at the start and faded in most people; the label builds up the dose slowly to limit it.

The main danger is severe hypoglycaemia, for which the US label carries a boxed warning. In the type 1 trials, in which insulin was not lowered at the start, 16.8% of people on pramlintide had an episode needing someone else's help in the first three months, against 10.8% on placebo, and 7.3% against 3.3% needed medical help such as glucagon or an emergency visit. In the dose-titration trial, in which mealtime insulin was cut at the start, those figures were 13.5% against 6.1% and 3.4% against 2.0%; in type 2 diabetes they were 8.2% against 2.1% and 1.7% against 0.7%. The label warns that such episodes can cause serious injury while driving or operating machinery.

The label rules it out for people with hypoglycaemia unawareness, confirmed gastroparesis or a serious allergy to the product, and says it should not be considered for children, for people with an HbA1c above 9% or recurrent severe hypoglycaemia in the past six months, for those who do not keep to their insulin and glucose monitoring, or for those who need drugs that speed up the gut. Because it slows stomach emptying, it can delay the absorption of tablets taken at the same time.

Injection-site reactions and pancreatitis have been reported since it reached the market. The controlled trials behind the approval lasted 26 to 52 weeks, safety and effectiveness in children have not been established, and the label calls the data in pregnancy insufficient to judge the risk.

Pramlintide and the newer amylin drugs

Pramlintide showed that amylin can work as a medicine, and also where its limits lay: an injection before every main meal, an extra fall in HbA1c of about 0.3 percentage points, and a risk of severe hypoglycaemia tied to insulin. The amylin drugs now in development keep the hormone's effect on appetite but are injected once a week and aimed at weight management.

Cagrilintide, from Novo Nordisk, keeps pramlintide's three prolines and adds a fatty-acid chain that stretches its half-life to about a week. It is in phase 3 trials on its own, and in combination with semaglutide, as CagriSema, it was filed with the FDA in December 2025. Three more once-weekly drugs that act on amylin receptors have entered phase 3: eloralintide (Eli Lilly) in December 2025; amycretin (Novo Nordisk, since renamed zenagamtide), a single molecule that also activates the GLP-1 receptor, in February 2026; and petrelintide (Zealand Pharma with Roche) in September 2026. None of them has been approved yet.

Frequently asked questions

Is Symlin still available?

Not as a new supply. AstraZeneca has discontinued US production and supply of SymlinPen, the last presentation on the market, and said in its notice that remaining stock would soon run out. The FDA approval of 2005 has not been withdrawn, but every Symlin product is listed as discontinued and no generic exists. In the EU Symlin was never authorised.

Can you get pramlintide in the Netherlands?

Not as a medicine. Pramlintide has never been registered in the Netherlands or authorised in the EU, so pharmacies do not stock it and basic insurance does not cover it. Pramlintide offered online as a research chemical is not a medicine: it has no marketing authorisation, its quality is not controlled under pharmaceutical rules, and it may not be sold or used for people. DutchPeptides does not sell it.

What is the difference between pramlintide and cagrilintide?

Both are analogues of amylin, and cagrilintide keeps pramlintide's three prolines. Pramlintide has a half-life under an hour, was injected before each main meal and was approved only as an add-on to mealtime insulin in diabetes. Cagrilintide, from Novo Nordisk, carries a fatty-acid chain, lasts about a week and is being developed for weight management, alone and with semaglutide as CagriSema. Neither is available as a medicine in the EU.

Does pramlintide cause weight loss?

A little, in the diabetes trials: people on pramlintide lost 0.4 to 1.6 kg over 6 to 12 months, while those on placebo gained weight. In a 4-month obesity trial with a lifestyle programme, weight fell 3.8 to 6.1 kg against 2.8 kg on placebo, and after a year the two regimens the authors singled out kept 6.1 and 7.2 kg more off than placebo. It was never approved for weight loss, and a combination with metreleptin for obesity was abandoned in 2011.

What are the side effects of pramlintide?

Mainly nausea, especially at the start: 48% against 17% on placebo in type 1 diabetes and 28% against 12% in type 2, followed by loss of appetite, vomiting and headache. The serious risk is severe hypoglycaemia when it is combined with insulin, usually within three hours of an injection, for which the US label carries a boxed warning. Injection-site reactions and pancreatitis have been reported since it came on the market.

Is pramlintide banned in sport?

It is not named on the WADA Prohibited List. The open question is class S0, which prohibits substances without a current approval for human therapeutic use. Symlin's FDA approval has not been withdrawn, although the product is no longer made. The English list mentions 'discontinued' drugs as an S0 example, which the Dopingautoriteit's Dutch translation describes as drugs whose development was stopped. We found no ruling on pramlintide itself, so athletes can check with the Dopingautoriteit, which applies the WADA list in the Netherlands.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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