Pramlintide: the approved amylin analogue

What pramlintide is

The Symlin® label describes pramlintide as a synthetic analogue of human amylin, made as a chain of 37 amino acids. It differs from the natural hormone at three positions, 25, 28 and 29, where the amino acid proline has been substituted ^[1]. The amylin article covers the hormone; this one covers the medicine.

Symlin® is a clear, sterile solution in disposable multidose pens called SymlinPen®, distributed in the US by AstraZeneca, and is injected under the skin ^[1].

Who the label is written for

Symlin® is approved as an extra treatment in type 1 or type 2 diabetes when someone already uses mealtime insulin and, even with well-managed insulin, has not reached the desired glucose control. It is not approved for weight management, and the label says its safety and effectiveness in children have not been established ^[1].

The label calls patient selection critical. It describes people under ongoing care from a professional experienced with insulin, supported by diabetes educators. It lists situations in which Symlin® should not be considered, including an HbA1c above 9%, repeated severe low blood sugar needing help in the past 6 months, being unable to sense low blood sugar, confirmed gastroparesis and poor adherence to insulin or glucose checks ^[1].

Two contraindications are absolute in the label: a previous serious allergic reaction to Symlin® or its ingredients, and confirmed gastroparesis, a condition in which the stomach empties too slowly ^[1]. For pregnancy, the label says human data are not enough to judge the risk, and the Medication Guide asks anyone pregnant or planning a pregnancy to talk to their provider ^[1].

How it acts

According to the label, amylin is stored with insulin in the same pancreatic cells and released with it at meals; in both types of diabetes, less of each is released after food ^[1].

In human studies described in the label, pramlintide slowed stomach emptying without changing how much of the food is absorbed overall, reduced the rise in glucagon after meals and affected satiety, leading to lower calorie intake. In a buffet study, a single dose given an hour before the meal reduced total calories by about a fifth compared with placebo. The label also reports that pramlintide did not change the body’s hormonal defence against insulin-induced low blood sugar ^[1].

How it differs from weekly GLP-1 medicines

• Timing: the label says Symlin® is injected just before each major meal, defined as at least 250 kcal or 30 grams of carbohydrate, rather than once a week ^[1].
• Half-life: in healthy people, pramlintide’s half-life is about 48 minutes ^[1]. For comparison, the Wegovy® label gives semaglutide an elimination half-life of about one week ^[2].
• Injection: the label names the abdomen or thigh and advises against the arm because absorption varies there. Each site should be different from the one used for insulin ^[1].
• Never mixed: Symlin® and insulin are always given as separate injections, because mixing them can change how both behave in the body ^[1].

The boxed warning: severe low blood sugar

Pramlintide alone does not cause low blood sugar, the label says, but it is always used with mealtime insulin, and together they raise the risk of severe hypoglycaemia, especially in type 1 diabetes. When it happens, it is seen within about 3 hours of the injection. Episodes while driving or using machinery can cause serious injury ^[1].

To lower that risk, the label tells prescribers to cut mealtime insulin by half when Symlin® is started, to check glucose often before and after meals and at bedtime, and to raise the Symlin® dose only in steps, after at least 3 days without significant nausea. The Medication Guide asks patients to agree a low blood sugar plan with their care team and keep fast-acting sugar or glucagon at hand ^[1].

Recognising low blood sugar, and what raises the risk

The Medication Guide lists the symptoms of low and severely low blood sugar as lightheadedness, dizziness, shakiness, sweating, hunger, a fast heartbeat, trouble concentrating or confusion, changes in vision, headache, irritability and drowsiness ^[1]. It asks people not to drive or operate machinery until they know how Symlin® affects them ^[1].

• Not reducing mealtime insulin as instructed, or using more Symlin® or insulin than prescribed ^[1].
• Changing an insulin dose without checking blood sugar ^[1].
• Eating less than a usual meal, being ill and unable to eat, or being more active than usual ^[1].
• Having low blood sugar before eating, or drinking alcohol ^[1].

Side effects in the trials

Most side effects in the label’s placebo-controlled trials involved the stomach. In type 1 diabetes, nausea affected 48% of people on Symlin® against 17% on placebo, loss of appetite 17% against 2%, and vomiting 11% against 7%. In type 2 diabetes on insulin, nausea affected 28% against 12% and headache 13% against 7% ^[1].

Nausea is most common early on, fades for most people, and is reduced by gradual dose increases. Redness, swelling or itching at the injection site usually settles within days to weeks. Average weight fell slightly in the trials, by about 0.8 to 1.6 kg, against small gains on placebo ^[1].

What reviews of the trials add

A 2011 systematic review and meta-analysis pooled eight randomised trials: four in type 2 diabetes, where everyone also used insulin, and four in people with obesity but no diabetes ^[6]. In type 2 diabetes pramlintide lowered HbA1c by about a third of a percentage point and weight by about 2.6 kg compared with control. Across both groups of trials, people on pramlintide were about 1.8 times as likely to report nausea; hypoglycaemia was not more frequent at any point ^[6]. The obesity trials studied a use that is not in the US label.

A 2021 network meta-analysis of 58 trials of drugs added to insulin in adults with type 1 diabetes found that pramlintide, like several other drugs, increased nausea, that no drug increased severe hypoglycaemia, and that confidence in the evidence was mostly moderate to very low ^[7]. Pooled analyses do not replace the label: the boxed warning and its precautions are what prescribers follow.

Other practical points from the label

• Other tablets: because stomach emptying slows, the label says oral medicines whose fast effect matters, such as pain relievers, antibiotics or oral contraceptives, may need to be taken at least 1 hour before or 2 hours after the injection. Ask your prescriber how this applies to you ^[1].
• Sharing: a SymlinPen® must never be shared, even with a new needle, because of the risk of passing on blood-borne infections ^[1].
• Storage: unused pens go in the refrigerator, protected from light and never frozen. Once in use, a pen can be refrigerated or kept up to 30°C (86°F) and must be used within 30 days ^[1].
• Supply: because both pens are listed as to be discontinued, anyone using Symlin® can ask their prescriber and pharmacist how long supply is expected to last and what the plan is ^[3][4].

Symlin® and SymlinPen® are registered trademarks of the AstraZeneca group of companies. Wegovy® is a registered trademark of Novo Nordisk A/S. PepLabo is not affiliated with or endorsed by AstraZeneca or Novo Nordisk.

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