Non-insulin Injectable Diabetes Medications

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Non-insulin Injectable Diabetes Medications

As you’ve learned over the past few months, there are numerous types of diabetes pills that can be effective in treating type 2 diabetes. But, thanks to the changing nature of this condition, over time, diabetes pills may not be enough to keep blood sugars and HbA1c within a safe range. In the past, the next step would be to start on insulin. And while many people do, indeed, go on insulin (and there’s nothing wrong with that), today, there are other options: these are the non-insulin injectable medications.

Amylin analog

Amylin is a hormone that is secreted along with insulin in response to food intake. In people with type 1 diabetes and people with type 2 diabetes who require insulin, both insulin and amylin is reduced due to the beta cells in the pancreas not working as they should.

The first non-insulin injectable drug for diabetes was approved by the FDA in 2005 — this drug was pramlintide (brand name Symlin), a synthetic form of amylin.

How it works

Pramlintide slows gastric emptying, blocks the release of glucagon (a hormone that raises blood sugar), reduces after-meal glucose release from the liver, and helps to reduce food intake, possibly leading to weight loss. The result? Less of a rise in blood sugars after eating a meal.

Who it’s for

Pramlintide is only used in people with diabetes who take insulin. People with type 2 diabetes can take this medication if they also take mealtime, or fast-acting, insulin.

How it’s taken

This drug must be injected before each major meal. It can’t be mixed with insulin, so it means taking more injections. Dosing is started low and gradually increased, as needed. Mealtime insulin doses usually need to be decreased to reduce the risk of low blood sugar. Pramlintide is available in a pen (much like an insulin pen).

Side effects

The main side effect of pramlintide is nausea, and this is why the dose is started low. Low blood sugar is another side effect, as it’s taken with insulin. Other side effects may include loss of appetite, fatigue, headache and weight loss.

GLP-1 receptor agonists

The other class of non-insulin injectables that is more widely used than the amylin analog is known as GLP-1 receptor agonists. The action of these drugs is based on incretins, which are gut hormones that work to increase insulin secretion in response to eating. Incretin hormones work in several ways: they increase satiety (feelings of fullness), slow stomach emptying, increase insulin release, and decrease glucagon release. Synthetic versions of these hormones are now available: The first drug in this class to be approved, in 2005, is exenatide.

Available GLP-1 receptor agonists are the following:

  • exenatide (Byetta and Bydureon)
  • liraglutide (Victoza)
  • albiglutide (Tanzeum)
  • dulaglutide (Trulicity)
  • lixisenatide (Adlyxin)
  • semaglutide (Ozempic, Rybelsus)

How they work

These medications work to help the pancreas release insulin after you eat. They also limit glucagon, and they slow down digestion, which helps to increase the feeling of fullness.

Who they’re for

GLP-1 receptor agonists are approved for people who have type 2 diabetes and who may not be having success with diabetes pills. People with type 2 diabetes can be taking long-acting (basal) insulin, but they’re not approved yet for those also taking mealtime insulin. And these drugs are not approved for people who have type 1 diabetes.

How they’re taken

GLP-1 agonists are taken by injection in the thigh, upper arm, or abdomen twice a day, once a day, or once a week, depending on the drug. Bydureon (which is an extended-release form of exenatide), Tanzeum, Trulicity and Ozempic are taken once per week.

Side effects

Nausea is the main side effect; others include vomiting, diarrhea, upset stomach, dizziness and headache. Low blood sugar can occur if you take insulin or pills that raise the risk for lows. Pancreatitis (inflammation of the pancreas) is a less common, but possible side effect, as well. Many people lose weight when taking these drugs; in fact; liraglutide has been approved (in a larger dose) as a weight-loss agent called Saxenda.


GLP-1 receptor agonists shouldn’t be used if you have a gastrointestinal disorder, such as gastroparesis. And if you have a personal or family history of thyroid cancer, you shouldn’t take these drugs.

You might be wondering why anyone would take these drugs, since they must be injected. These drugs do lower HbA1c levels, but only by 0.5% to 1.5%. They’re also only used as a second or third agent, not by themselves. One of the main draws of these drugs is that they do lead to weight loss in about 80% of users, and they seem to curb hunger, making it a good choice for people who constantly feel hungry. Weight loss eventually plateaus, however, so keep that in mind.

Are one of these options for you? Talk with your doctor to find out. Also, check into your health-plan coverage, as well, as these can be costly medicines.

Want to learn more about the role of medicines in treating diabetes? Read the rest of diabetes educator Amy Campbell’s eight-part series on diabetes drugs, covering metforminsulfonylureasmeglitinidesthiazolidinedionesDPP-4 inhibitorsSGLT2 inhibitorsalpha-glucosidase inhibitorsbile acid sequestrants and dopamine receptor agonists, and insulin.

Originally Published September 14, 2015

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