November 27, 2015
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Diabetes Treatment (cont.)

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Pramlintide (Symlin)

Pramlintide (Symlin) was the first in a class of injectable, anti-hyperglycemic medications for use in addition to insulin for type 1 diabetes or type 2 diabetes. Pramlintide, the active ingredient in Symlin, is a synthetic analog of human amylin, a naturally occurring neuroendocrine hormone synthesized by pancreatic beta-cells that helps control glucose after meals. Similar to insulin, amylin is absent or deficient in person with diabetes. When used with insulin, amylin can improve glycemic control and has additional benefits that cannot be realized with insulin alone.

According to published data, pramlintide reduces post-meal blood sugar peaks, reduces glucose fluctuations throughout the day, enhances satiety (the sensation of fullness) leading to potential weight loss, and lowers mealtime insulin requirements. Pramlintide can improve HbA1c beyond the effect of insulin alone.

Pramlintide is administered by injection just prior to meals (three times each day) for:

  • Type 1 diabetes as an additional treatment to mealtime insulin therapy for those failing to achieve desired glucose control despite optimal insulin therapy.
  • Type 2 diabetes as an additional treatment to mealtime insulin therapy for those failing to achieve desired glucose control despite optimal insulin therapy, with or without a concurrent sulfonylurea agent and/or metformin.

Pramlintide warnings and side effects

Pramlintide with insulin has been associated with an increased risk of insulin-induced severe hypoglycemia, particularly in type 1 diabetes. This severe hypoglycemia occurs within 3 hours of injecting pramlintide.

The major side effects of pramlintide are:

  • nausea, which can be reduced by slowly and steadily increasing the dose, and
  • hypoglycemia (dangerously low levels of blood sugar). To avoid hypoglycemia, the dose of mealtime insulin should be cut in half when starting pramlintide. Brief placebo-controlled clinical studies (up to six months) reported weight loss over six pounds associated with pramlintide therapy.

Exenatide (Byetta)

Exenatide (Byetta) originated from an interesting source: the saliva of the Gila monster! Scientists observed that this small lizard could go a long time without eating. They discovered a substance in its saliva that slowed stomach emptying, thus making the lizard feel fuller for a longer time. This substance resembled a gut hormone naturally found in humans known as glucagon-like peptide-1 (GLP-1). The enzyme DPP-IV breaks down GLP-If one could make a substance like GLP-1 but that resisted breakdown, it would have potential benefit. Such efforts developed exenatide.

Exenatide is the first in the incretin mimetic class of drugs for type 2 diabetes. Exenatide shares many therapeutic properties with GLP-1, and it mimics natural physiology for self-regulating blood sugar. Namely, exenatide slows stomach emptying and slows the release of glucose from the liver, thereby regulating delivery of nutrients to the intestine for absorption. Exenatide also works centrally in the brain to regulate hunger.

Exenatide is indicated as additional therapy to improve control of blood sugar in type 2 diabetes patients who have not achieved adequate sugar control with metformin, sulfonylurea, or a combination of metformin and sulfonylurea. Exenatide enhances insulin release from the pancreas. Insulin secretion usually increases only when blood sugars are high, then decreases as blood sugar level approaches normal. In addition to enhancing the normal physiology of the pancreatic beta-cell, exenatide suppresses glucose release from the liver, slows stomach emptying, slows absorption of nutrients including carbohydrate, and reduces food intake.

Like pramlintide, exenatide is injected but only twice each day (usually before breakfast and dinner meals). Exenatide is available by a disposable pen form and in two doses. The initial goal is to start a lower dose for a month or so, then move up to the higher dose if needed and as tolerated. Similar to pramlintide, the main side effect of exenatide is nausea, most likely due to its effects on stomach emptying. Exenatide is temperature sensitive, so the initial recommendation was to store pens at 36 F to 46 F (2 C to 8 C). This recommendation recently changed. Unopened pens should be refrigerated; once opened, exenatide pens can be left at room temperature. The risk of hypoglycemia remains a possibility with exenatide, especially when used in combination with sulfonylurea. Your health-care professional may choose to decrease the dose of other medications while initially evaluating your response to exenatide.

Similar to pramlintide, weight reduction is seen with exenatide in most patients. This makes exenatide particularly suitable for the typical type 2 diabetes patient who is also overweight.

FDA is currently considering a longer acting from of exenatide for approval. This new formulation could carry similar benefits and side effects, but with less frequent injections.

Medically Reviewed by a Doctor on 5/7/2015


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