The differences between GLP1a non-insulin injectables: which one is right for you?

by Jessica Pyhtila, PharmD, BCPS, BCGP

Over the past decade, GLP1a non-insulin injectable products have revolutionized diabetes management. Compared to insulin, they cause less hypoglycemia and often need to be given less frequently than insulin. As of 2022, many different GLP1a products are available. But what is the best way to know which one is right for you? In this article, we will compare and contrast the GLP1a injectable products so that you and your doctor can make the best choice of drug.

What is a GLP1a?

GLP1a is short for “glucagon-like peptide-1 agonist.” These drugs work by mimicking the body’s natural GLP1 (glucagon-like peptide-1) hormones. Under normal circumstances, GLP1 binds to the cell receptors for GLP1 in the pancreas, stimulating the release of insulin. However, in people with type 2 diabetes, the body doesn’t efficiently release GLP1, making the GLP1a products useful to simulate this natural process.

However, relying on insulin release from GLP1a products is different from relying on injectable insulin. Unlike insulin, which will reduce your blood sugar no matter what, GLP1 only works when blood sugar is elevated, like after a meal. This means that GLP1s have a reduced risk of hypoglycemia compared to insulin, as they do not stimulate insulin release when your blood sugar is already low.

GLP1a products have a variety of effects that can benefit people with diabetes. They can:

  • Improve hemoglobin A1c by around 1%
  • Slow the stomach’s emptying into the intestines. This leads to less of a spike in blood sugar after meals as food takes longer to digest.
  • Protect the beta cells in the pancreas that release insulin into the bloodstream
  • Stop the pancreas from releasing glucagon (a substance that increases blood sugar) when your blood sugar is already high
  • Promote weight loss
  • Lower blood pressure
  • Reduce cholesterol
  • Improve heart health, including the heart’s ability to pump blood, its contraction, blood flow, and the health of cells in the heart
  • Decrease the risk of cardiovascular disease and death, especially liraglutide, dulaglutide, and semaglutide

It is for this reason that the American Diabetes Association recommends GLP1a agents second only to metformin for most people with type 2 diabetes, and recommends GLP1a products be considered before insulin. The GLP1a products currently available in the United States include:

  • Exenatide
  • Lixisenatide
  • Liraglutide
  • Dulaglutide
  • Semaglutide

Previously, another GLP1 product, albiglutide (Tanzeum) was available. However, the drug was withdrawn by its manufacturer in 2018 due to poor sales.

Comparing and Contrasting GLP1a Products

The five GLP1a agents that are currently available have many differences. Although they are all members of the same drug class, they differ in important ways including frequency of administration. Knowing these differences can not only help you tell the products apart from each other, but also help you to select which product may fit best with your needs.

In addition, while this article focuses on non-insulin injectable GLP1a products for diabetes, it is important to note that one GLP1a agent is available as an oral agent. Further, two GLP1a products are available specifically for weight loss, and two others are available as combination products with insulin. 

  Exenatide Lixisenatide Liraglutide Dulaglutide Semaglutide
Brand name for injectable product for diabetes Bydureon , Byetta Adlyxin Victoza Trulicity Ozempic
How often to administer for diabetes? Twice daily (Byetta) or once weekly (Bydureon) Once daily Once daily Once weekly Once weekly
Available as an oral product for diabetes? No No No No Yes, as Rybelsus
Available as an injectable combination with insulin for diabetes? No Yes, with insulin glargine as Soliqua 100/33 Yes, with insulin degludec as Xultophy No No
Available as an injectable product for weight loss? No No Yes, as Saxenda No Yes, as Wegovy
How injectable diabetes product is supplied Prefilled pen with a built-in needle (Bydureon)   Prefilled pen with separate removable needles that must be screwed on before administration (Byetta) Prefilled pen with separate removable needles that must be screwed on before administration Prefilled pen with separate removable needles that must be screwed on before administration Prefilled pen with a built-in needle Prefilled pen with separate removable needles that must be screwed on before administration
Dose automatically set, or user must dial dose? Dose automatically set (Bydureon)   User must dial to the correct dose before administration (Byetta) Dose automatically set User must dial to the correct dose before administration Dose automatically set User must dial to the correct dose before administration

Which GLP1a product offers the best A1c lowering?

On average, GLP1a drugs can reduce A1c by an average of 1%. However, studies show that some GLP1a agents tend to lower A1c more than others.

In general, semaglutide (Ozempic) causes the most reduction in A1c, followed by dulaglutide (Trulicity) and liraglutide (Victoza) which have roughly the same impact on A1c. This is followed by long-acting exenatide (Bydureon), then short-acting exenatide (Byetta), which causes around the same A1c lowering as lixisenatide (Adlyxin).

How do GLP1a products compare in terms of safety?

GLP1a agents are generally safe and effective. However, some people should avoid these products, including those who:

  • Are pregnant. Women of childbearing age should use contraception while taking a GLP1a drug.
  • Have gastrointestinal diseases like gastroparesis or inflammatory bowel disease
  • Have a personal or family history of multiple endocrine neoplasia 2A, multiple endocrine neoplasia 2B, or medullary thyroid cancer
  • Have a history of pancreatitis

How do GLP1a products compare in terms of side effects?

GLP1a agents are similar in regard to side effects. Generally, the most common side effects include:

  • Nausea
  • Vomiting
  • Diarrhea

However, side effects are more likely with certain products than others. For example, side effects are more likely to occur with short-acting exenatide (Byetta) and semaglutide (Ozempic), and are less likely to occur with long-acting exenatide (Bydureon).

Which GLP1a product is best for weight loss?

Although all GLP1a products can cause weight loss, studies have shown wide variations in exactly how much weight loss to expect. On average, people starting a GLP1a drug lose about 6.4 lbs. However, some agents are more likely to cause greater weight loss than others.

Overall, semaglutide (Ozempic) causes the most weight loss. This is followed by liraglutide (Victoza), then dulaglutide (Trulicity).

Lixisenatide (Adlyxin) and exenatide (Byetta and Bydureon) typically cause the least amount of weight loss.

The various GLP1a agents that have come out over the past few years are powerful tools to help you manage your diabetes. Depending on your health needs, one agent may be a better fit for you than others. Your doctor can help you choose which, if any, GLP1a may be most appropriate for you.

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