GLP-1 agonist, like Byetta and Bydureon can help treat Type 2 Diabetes

GLP-1 agonists are a group of medications that mimic the actions of glucagon-like peptide or GLP-1. GLP-1 is one of several naturally occurring incretin compounds that affect the body after they are released from the gut during digestion. Because of its name, GLP-1 might seem to act like glucagon that increases glucose production by the liver and raises glucose levels. Instead, GLP-1 lowers both glucose and glucagon levels. Despite their different actions, GLP-1 and glucagon are both derived from the same parent compound called proglucagon, hence the similarity in names.

GLP-1 cannot be used as a drug because it is broken down in less than 2 minutes by an enzyme called DPP-4 found throughout the body. To overcome this problem, GLP-1 agonists have been developed to act like GLP-1 but not be broken down as quickly.

GLP-1 agonists and natural GLP-1 work on several different organs to lower glucose levels. They:

  1. Slow glucose absorption from the gut (Type 1 and Type 2)
  2. Increase insulin secretion from the pancreas when the glucose is high (Type 2)
  3. Lower glucagon levels after meals (Type 1 and Type 2)
  4. Suppress a receptor located in the hypothalamus to reduce appetite (Type 1 and Type 2)
  5. Increase beta cell mass and first phase insulin release so more insulin reaches the liver and blood more quickly (Type 2)

GLP-1 agonists lower glucose levels and improve control for those on insulin, and can often substantially delay the need to start insulin in those with Type 2 diabetes. They carry a low risk of hypoglycemia, promote weight loss, and show improvements in beta cell function, lipid levels, and blood pressure. However, like other diabetes medications, they cannot compete with insulin at lowering glucose levels. Used by themselves or with insulin, they greatly improve post-meal glucose levels for most users.

GLP-1 agonists, along with glitazones, DPP-4 inhibitors, and insulin, help delay the progression of Type 2 diabetes through protection of beta cells, lessening of insulin resistance, or preservation of insulin production. This makes it easier to control glucose levels and delays or reduces the need for insulin. They appear do this over several years when used in early Type 2 diabetes.

Insulin production in the pancreas in people with Type 2 diabetes is greatly reduced by the time diabetes is diagnosed, so any medication that improves insulin production and lowers glucose levels is very helpful. Unlike glitazone medications that reduce insulin resistance, GLP-1 agonists do not affect insulin resistance often found in Type 2 Diabetes. Because of their distinct protective actions, these two classes of drugs may have additive effects that protect the beta cells. Studies on this are underway.

Both GLP-1 agonists and glitazones have been shown to slow down the loss of insulin production that is a primary cause for rising glucose levels over time and forces many with Type 2 diabetes to require insulin. In his 2008 Banting Lecture to the American Diabetes Association, Dr. Ralph DeFronzo, a diabetes specialist and researcher at the University of Texas Health and Science Center in San Antonio, recommended that these two medication classes be considered first when treating Type 2 diabetes because they preserve beta cell function, and that they might be considered in those who have pre-diabetes due to their capacity to protect beta cells.

Unfortunately, GLP-1 agonists do not maintain insulin production in Type 1 or Type 1.5 diabetes. Here, diabetes is caused by an antibody attack by the immune system that gradually destroys the beta cells that make insulin. GLP-1 agonists cannot stop this process.

The original drug in this class, Byetta (exenatide, given as two injections a day), was derived from a compound found in the saliva of the Gila monster, a lizard that lives in the southwestern US. This Gila spit compound has a structure similar to GLP-1 but is broken down more slowly by the enzyme DPP-4. Byetta received FDA approval in 2005. A second unrelated GLP-1 agonist Victoza (liraglutide, given as one injection a day) became available in 2010. Bydureon (exenatide extended-release, given as one injection a week after being mixed) received approval in 2012, and was followed by approval for a Bydureon pen (one injection a week, easier to mix) that should become available in the second half of 2014. Additional GLP-1 agonists are being developed.

Only Victoza has been approved for use with long-acting insulins. No GLP-1 agonist has been approved for use with rapid-acting insulins because the primary action of both is to lower glucose levels after meals. However, GLP-1 agonist actions complement nicely the actions of both fast and long-acting insulin injections, once doses have been appropriately reduced.

In clinical studies, GLP-1 agonists improve fasting and post meal glucose levels in Type 1 diabetes and aid some users to lose excess pounds. GLP-1 agonists allow insulin production to shut off as the glucose level approaches normal, so they do not directly cause hypoglycemia, although this can happen if combined with an excess of a sulfonylurea or insulin.

GLP-1 agonists slow down the transit of drugs through the intestine, so they may also alter the action times of other medications you are taking. They are stored between 36-46°F (2-8°C), protected from direct sunlight, and never used once frozen. The pen should be discarded 30 days after first use. GLP-1 agonists are not approved for use in pregnant women or nursing mothers, and their effects on a fetus are unknown.

Side Effects

The most common side effects of GLP-1 agonists are a feeling of fullness, nausea, and diarrhea. Nausea does not appear to be related to dose size and usually disappears after a couple of weeks. Side effects usually decrease in most people and less than one in ten users stops these medication for this reason. Users may experience decreased appetite, acid reflux, headaches, or increased sweating. Immune system reactions occasionally occur with skin hives being the most common.

GLP-1 agonists may be rarely associated with hemorrhagic or necrotizing pancreatitis, a very serious illness that involves a gradual destruction of the pancreas. Your doctor should be called and the medication stopped immediately if unusual abdominal pain or intestinal problems occur. Although there was some concern initially about pancreatic cancer, large subsequent studies have found no link between GLP-1s and pancreatic cancer.


  1. Less glucose variability with fewer highs and lows
  2. Lower post-meal glucose levels, some lowering of the fasting glucose
  3. Often helps weight loss
  4. Does not cause hypoglycemia unless insulin or sulfonylurea doses are excessive
  5. May improve and preserve the health of the beta cell, and delay or lessen the need for injected insulin in Type 2 diabetes
  6. OK with liver or heart problems


  1. Must be taken by injection. Byetta (exenatide) twice daily, Victoza (liraglutide) once daily, and Bydureon (extended release exenatide) once a week. Cannot be mixed with insulin
  2.  Not FDA approved for Type 1 diabetes, although research studies suggest some benefits
  3. Nausea or vomiting may occur at first, usually resolves
  4. People with gastrointestinal problems or moderate to severe kidney disease are not good candidates
  5. Responses to GLP-1 agonists vary widely from person to person
  6. Those who abuse alcohol, have a history of pancreatitis, or a history of gallbladder disease may be more likely to develop pancreatitis.
  7. Itching or discomfort at an injection site may occur, as well as occasional bruising.

Great Books on Medications

Until There Is A Cure Medical Management of Type 1 Diabetes Medical Management of Type 2 Diabetes

Until There Is A Cure

For more easy-to-understand information on diabetes medications to use with or without insulin, see this clear, up-to-date book written for the person with diabetes. Written by Gary Scheiner, MS, CDE.

Medical Management of
Type 1 Diabetes

Published by the American Diabetes Association in 2012, this highly detailed professional book edited by Francine R. Kaufman, MD provides the most current information about all aspects of Type 1 diabetes. Discover the full picture on how to use medications and insulin for people with Type 1.

Medical Management of
Type 2 Diabetes

Published by the American Diabetes Association in 2012, this professional companion to the Type 1 book is a comprehensive presentation of many of the ways insulin and medications can be used alone and together.