Pramlintide

Pramlintide is a synthetic drug based on the hormone amylin, which is released by the pancreas. Amylin helps regulate carbohydrate and fat metabolism, and it is deficient in people with diabetes. Pramlintide is used to replace amylin in people with type 1 and type 2 diabetes. The Food and Drug Administration approved the use of pramlintide on March 17, 2005. Pramlintide was developed by Amylin Pharmaceuticals and is co-marketed as Symlin by Amylin and Eli-Lily.

box and vial of Symlin

Uses

Pramlintide is for people with type 1 or type 2 diabetes to help lower blood sugar, especially high blood sugar that happens after meals. It is not a replacement for insulin, but may lower the amount of insulin needed to control blood sugar. It is used in people for whom insulin by itself has not controlled blood sugar satisfactorily. Frequent blood sugar monitoring is necessary, along with dose adjustments, while receiving pramlintide and insulin.

How Pramlintide Is Taken

Pramlintide is injected subcutaneously (under the skin) in the abdomen or thigh using either insulin syringes or a prefilled pen injector device. On first starting the drug, a "start low, go slow" schedule of low initial dose and gradual dose escalation can be used to prevent severe nausea.

Pramlintide is administered via syringes marked in "units" of U-100 insulin (where 1 unit = 10 µl). It is formulated at 6 mg/ml. Therefore, conversion of µg (micrograms) to units is necessary to inject the proper dose. For example, to inject 60 µg of pramlintide, 10 units of fluid are drawn up in a U-100 insulin syringe.

How Pramlintide Works

Pramlintide is thought to work like amylin. Pramlintide, like amylin, reduces caloric intake, reduces glucagon secretion, and slows emptying of the stomach. Pramlintide mediates these effects by acting in regions of the brain that are sensitive to the amount of sugar in the blood.

How the Body Affects Pramlintide

Pramlintide reaches a maximum concentration in the blood approximately 20 minutes after injection. The time needed for the concentration in the blood to be reduced by half, the half-life, is approximately 50 minutes. Most pramlintide is excreted in the urine.

Pramlintide itself does not have any effect on the body. Rather, the kidneys convert pramlintide into its active form.

Side Effects

Gastrointestinal side effects (nausea, vomiting, decreased appetite) are most prominent early in the course of therapy and are the most frequent cause of discontinuation. Some other side effects include the following:

• stomach pain
• tiredness
• dizziness
• indigestion
• reactions at the injection site (e.g., redness, minor bruising, or pain)

Benefits

Pramlintide helps reduce after-meal blood sugar spikes (postprandial hyperglycemia). It also reduces blood sugar fluctuations through the day and reduces [[glycosylated hemoglobin]] (HbA1C) levels. Symlin also leads to early satiety (a feeling of fullness after eating) by keeping food in the stomach longer, and so may help people eat less and lose weight.

Risks and Precautions

Low blood sugar (hypoglycemia): People taking insulin may find that insulin dose reduction is necessary to avoid hypoglycemia.

Drug Interactions

Pramlintide slows emptying of the stomach. This could slow the absorption of some other drugs taken with pramlintide. This interaction is more important for drugs that rely on a rapid onset of action because it could delay the effect of some drugs.

History

The discovery of insulin was a turning point in treatment of type 1 diabetes mellitus, which until then had consisted of ineffectual starvation diets followed inevitably by coma and death. Investigators hypothesized that insulin, while profoundly important, was not the only hormone released by the pancreas. Amylin was described in 1988 by researchers at Oxford University who found a second molecule that circulated in the blood alongside insulin and controlled metabolism of carbohydrates, fats and proteins^[1]. To exploit this discovery, Amylin Pharmaceuticals was formed soon afterward to develop a genetically engineered version of the eponymous hormone. To make the more stable and appropriate for use as a drug, researchers at the company slightly modified the hormone and named the new molecule "pramlintide"

Amylin formed a collaboration agreement with Eli Lilly and Company to manufacture and market the drug, taking advantage of Lilly's expertise in insulin manufacturing and its standing in the diabetes community.

Research

Recent research has supported the use of pramlintide for achieving weight loss both in obese^[2] and normal-weight^[3] individuals. The drug has also shown potential cardiovascular benefits by reducing biomarkers of cardiovascular risk in patients with type 2 diabetes^[4].

Clinical Trials

Clinical trials involving pramlintide are listed at here.

Interesting Facts

Like other drugs based on large protein molecules, Symlin is not inexpensive. The average wholesale price of pramlintide is $95.40/month. ^[5]

Free, Full-Text Review Articles

Schmitz O, Brock B, Rungby J. Amylin agonists: a novel approach in the treatment of diabetes. Diabetes. 2004 Dec;53 Suppl 3:S233-8. Abstract| Full Text | PDF

References

1. ↑ Cooper GJ, Leighton B, Dimitriadis GD, et al., Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7763-6. Abstract | PDF
2. ↑ Aronne L, Fujioka K, Aroda V, et al. Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study. J Clin Endocrinol Metab. 2007 Aug;92(8):2977-83. Abstract
3. ↑ Chapman I, Parker B, Doran S, et al., Low-dose pramlintide reduced food intake and meal duration in healthy, normal-weight subjects. Obesity (Silver Spring). 2007 May;15(5):1179-86. Abstract
4. ↑ Wysham C, Lush C, Zhang B, Maier H, Wilhelm K. Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes. Curr Med Res Opin. 2008 Jan;24(1):79-85. Abstract
5. ↑ Red Book Update 2006; 25(9) (Montvale, NJ: Thomson PDR; 2006)