Exenatide (Byetta) and pramlintide (Symlin) are both injectable drugs taken at mealtimes. Byetta is the first of a class of drugs known as incretin mimetics that work by “mimicking” the action of hormones called incretins, which are key in regulating blood glucose levels. Symlin is a synthetic version of amylin, a neuroendocrine hormone (i.e., hormones that regulate interactions between the endocrine and nervous systems) that also plays a major role in blood glucose regulation.

Byetta is approved for use either by itself or in combination with metformin, a sulfonylurea, a TZD, or a combination of the three. It is usually prescribed when a patient is unable to achieve control with oral medications alone. Byetta is not a substitute for insulin, and type 2 patients who are already on insulin should not forgo insulin to try Byetta.

Injections are taken twice daily up to an hour before a major meal. Most people prefer to take it before breakfast and dinner, but any two mealtimes are fine as long as there are six hours between them. An extended-release formulation of the drug, designed for once-weekly injections, was in clinical trials as of early 2008.

Unlike Byetta, Symlin is used as an adjunct (or companion) treatment to insulin. It is available in vials and pens, and is injected right before any major meal (i.e., at least 30 grams of carbs and/or 250 calories). While both rapid-acting insulin and Symlin may be injected prior to a meal, insulin and Symlin should never be administered in the same syringe, as mixing these drugs alters the chemical composition of Symlin. If your doctor starts you on Symlin, he will reduce your premeal insulin dose by up to 50 percent, depending on the type of insulin you use.

Symlin is also used in the treatment of type 1 diabetes.

How They Work

Byetta and Symlin have some similar features. First, they both slow the rate of digestion and send “all full” signals to the brain that promote feelings of satiety. They also both help control blood glucose levels by surpressing glucogon production by the liver.

Byetta also has an additional trick up its sleeve. It helps to stimulate insulin production in the pancreas. It only acts when elevated blood glucose is detected, so it does not cause low blood sugars. Byetta mimics the action of the incretin GLP-1, which is secreted by the intestines in response to food digestion. Incretins help to stimulate insulin production in the pancreas, and certain types of incretins also work to suppress glucagon production in the pancreas.

Byetta can also restore what is known as first phase insulin response — high levels of insulin secretion that occur in the first ten minutes after glucose is detected. People with type 2 diabetes frequently lose this capacity.

Side Effects

While Byetta and Symlin are not designed or FDA-approved as weight-loss drugs, one of the side effects of both medications is weight loss. In clinical trials, people on Byetta lost an average of five pounds in thirty weeks. Nausea is one of the most reported side effects of both Byetta and Symlin, which may explain why weight loss occurs.

Because Byetta and Symlin slow gastric emptying, they should not be used by people with gastroparesis. They can also slow the absorption of other drugs and consequently affect their therapeutic action, so make sure your health care team is aware if you start treatment on either of these medications.

Byetta is not recommended for use in patients with severe renal impairment or end-stage renal disease. There have also been postmarket reports (patient reports that occur after a drug has been FDA-approved) of pancreatitis in some Byetta users. Severe abdominal pain, sometimes with vomiting, is the main symptom of pancreatitis; if you experience this while on Byetta, let your doctor know immediately.

People who take Symlin are at higher risk of hypoglycemia, in part because the medication is used in conjunction with insulin. Your doctor may recommend that when you first start on Symlin, or when you adjust doses, you refrain from driving or operating heavy machinery up to three hours after taking a Symlin injection. You should also test frequently during this time. Insulin doses often have to be adjusted after initiation of Symlin therapy, so testing and logging results is particularly important during this time.