Tag Archives: exenatide

FDA Approves Exenatide for Once Weekly Use

Once-weekly injection of exenatide, sold in the U.S. as Bydureon, has been approved for use by the U.S. Food and Drug Administration.  It’s main competitors are Byetta (exenatide  injected twice daily) and Victoza  (liraglutide).  Byetta  and Bydureon are made by the same company, Amylin Pharmaceuticals.  Bydureon apparently is a slow-release formulation of exenatide.

Victoza is the one that celebrity chef Paula Deen endorsed about a month ago, around the same time she revealed she’s had type 2 diabetes for three years.  Victoza’s injected once daily.

The New York Times has a January 27, 2012, article on Bydureon, focusing on business and investing.  The new drug is expected to retail for $4,200 (USD) a year. 

Click for complete prescribing information.

Click for a press release approved by Amylin.

David Mendosa is excited about Bydureon.

These drugs are in a class called GLP-1 receptor agonists, which mimic the effect of glucagonlike peptide- 1, a hormone that increases insulin secretion by the pancreas when blood sugar levels are high.  They are prescribed as adjuncts to diet and exercise in adults with type 2 diabetes.

Steve Parker, M.D.

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Drug Review: GLP-1 Analogues (exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide)

GLP-1 analogues available in the U.S. are exenatide (sold as Byetta and Bydureon), liraglutide (sold as Victoza), albiglutide (Tanzeum), dulaglutide (Trulicity), and lixisenatide (Adlyxin).  They are sometimes referred to as GLP-1 receptor agonists.  They are not considered first-choice drugs, but instead are typically used in combination with other drugs, in conjuction with diet and exercise.

Remember that drug names vary by country and manufacturer.  This is a brief review only; consult your physician or pharmacist for full details.

Fun Fact for the diabetic version of  Trivial Pursuit:

Exenatide  (Byetta and Bydureon) is a synthesized version of a protein initially discovered in the saliva of a lizard, the Gila monster.

How do they work?

It’s complicated.

First off, you need to know that a small intestine hormone, glucagon-like peptide-1 (GLP-1), is produced in response to a meal.  This hormone increases insulin secretion by pancreas beta cells, suppresses glucagon after meals, inhibits emptying of the stomach, and inhibits appetite. Other effects are suppression of glucose production by the liver, and improved glucose uptake by tissues outside the liver.  All this tends to lower blood sugar levels after meals.

The problem is that GLP-1 is quickly destroyed by an enzyme called DPP-4.  We have available to us now chemicals similar to GLP-1, called GLP-1 analogues, that bind to the GLP-1 receptors and are resistant to degradation by the enzyme DPP-4.  They essentially act like GLP-1, and they hang around longer.

GLP-1 levels, by the way, are decreased in type 2 diabetes.

The action of GLP-1 is dependent on blood sugar levels.  If blood glucose is not elevated, GLP-1 doesn’t go to work.  From a practical viewpoint, this means that GLP-1-based therapies rarely cause hypoglycemia.

We know little about long-term outcomes with these drugs, such as diabetic complications, health-related quality of life, or mortality.


Exenatide (Byetta)  is FDA-approved for adults with type 2 diabetes who are not adequately controlled with metformin, sulfonylurea, or a thiazolidinedione (or a combination of these agents).  So it’s an add-on drug, not approved for use by itself.  In October, 2011, the FDA extended approval as an add-on therapy to insulin glargine (for example, Lantus in the U.S.), with or without metformin and/or a thiazolidinedione (TZD), in conjunction with diet and exercise for adults with type 2 diabetes who are not achieving adequate glycemic control on insulin glargine alone.

Once-weely exenatide (Bydureon) was FDA-approved in January, 2012.  Use with insulin has not been studied and is not recommended.  Don’t use along with Byetta.  Surprisingly, I found nothing in the drug package insert Feb.2, 2012, regarding whether it can be used with other diabetes drugs.  See comments in the preceding paragraph regarding standard twice-daily exenatide.  I suspect Bydureon can be used with metformin, sulfonylurea, thiazolidinedione, and insulin glargine (Lantus), but the package insert is not at all clear.

Liraglutide is FDA-approved for treatment of type 2 diabetes but is not recommended as initial therapy, although it does seem to be approved for use by itself.  It has been used alone and also in combination with metformin, sulfonylurea, and/or thiazolidinediones.  It’s not approved for use with insulin therapy.

Albiglutide is a once-weekly subcutaneous injection for type 2 diabetes. It was FDA-approved in 2014. It’s not recommended as initial drug therapy, although it is approved for use by itself. It can be used in combination with metformin, sulfonylurea, thiazolidinediones, and/or insulin.

Dulaglutide is also a once-weekly injection for adults with type 2 diabetes, approved by the FDA in2014.  It’s not a first-line drug, but can be used by itself or with metformin, glimiperide (and presumably other sulfonylureas), pioglitazone, and insulin lisper (e.g., Humalog, a rapid-acting insulin).

Lixisenatide is a daily injection for adults with type 2 diabetes. It can be used alone or in combination with metformin, sulfonylurea, thiazolidinedione (e.g., pioglitazone), or long-acting insulin (insulin glargine). Clinical trials did not include short-acting insulin.

You can assume none of these have been tested for safety in pregnant or nursing mothers.


They are available only as subcutaneous injections.  Exenatide is twice daily, starting at 5 mcg within 60 minutes prior to a meal.  After one month, the dose may be increased to 10 mcg twice daily.

Extended-release exenatide (Bydureon): 2 mg subcutaneous injection every seven days.

Liraglutide is a once daily subcutaneous injection starting at 0.6 mg, increasing to 1.2 mg after one week.  It is given without regard to meals.  Maximum dose is 1.8 mg/day.

Albiglutide is started at 30 mg subcutaneously every seven days and may be increased to 50 mg if needed.

Start dulaglutide at 0.75 mg weekly, increasing to 1.5 mg weekly if needed.

Lixisenatide starts at 10 mcg daily for 14 days then increases to 20 mcg daily.

Side Effects

GLP-1 analogues tend to cause nausea, vomiting, and diarrhea in as many as four in 10 users.  The nausea typically improves over time.  Compared with Byetta, Bydureon seems to cause less nausea.  They tend to cause weight loss.  These drugs might cause pancreatitis, which is life-threatening.  When used with insulin or an insulin secretagogue (like sulfonylureas or meglitinides), hypoglycemia may occur.

Hypoglycemia is rare when GLP-1 analogues are used as the sole diabetes drug, but still possible (0-5% risk?). When it happens, it’s rarely severe.

Liraglutide, albiglutide, and dulaglutide might cause thyroid cancer or thyroid tumors.   

Don’t use if you have . . .

… severe kidney impairment (exenatide), end-stage renal disease (lixisenatide),Multiple Endocrine Neoplasia syndrome (liraglutide), Multiple Endocrine Neoplasia syndrome type 2 (albiglutide, dulaglutide), or family history of medullary thyroid cancer (liraglutide, albiglutide, dulaglutide), or personal history or medullary thyroid cancer (albiglutide, dulaglutide).

Use GLP-1 analogues with caution or avoid entirely if you have a history of pancreatitis or gastroparesis. Don’t use dulaglutide if you have pre-existing severe gastrointestinal disease.

Use liraglutide with caution in patients with kidney or liver impairment. Dulaglutide is risky in the setting of liver impairment.

Don’t use any of these to treat diabetic ketoacidosis.

Steve Parker, M.D.

Last modification date: July 29, 2016

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The Holy Grail of Diabetes Treatment: Preserving Beta Cell Function

 A Nobel Prize in Medicine belongs to whoever (whomever?) figures out how to reliably and affordably protect and preserve beta cell function starting early in the course of type 2 diabetes.  Or type 1 diabetes, for that matter.

Dietary carbohydrates lead to secretion of insulin into the bloodstream by the pancreas’s beta cells.  The insulin limits and reverses the rise in blood sugar that results from digestion of carbohydrates.  If blood sugar rises too high, it damages our bodies. 

Type 2 diabetes is a disorder of carbohydrate metabolism.  Insulin from the beta cells isn’t doing its job adequately because tissues that should be taking up bloodstream sugar are resistant to insulin’s effect of driving sugar into the cells.  The beta cells pump out increasing amounts of insulin, trying to overcome the resistance of the tissues.  Eventually the beta cells become exhausted or “burned out,” reflected in diminished beta cell mass.  This situation has usually been present for years before type 2 diabetes is formally diagnosed.  This scenario is a leading theory of the development of type 2 diabetes.

Type 2 diabetes is considered by most physicians to be a progressive illness, requiring more and more drugs to control as the years pass.  That’s because the beta cells are dying off or otherwise becoming totally nonfunctional.  Once they’re gone, it’s hard (impossible?) to get them back.  If diabetes could be diagnosed early on, we’d find healthier beta cells to work with.  Perhaps we could strengthen or protect them.  This is what beta cell preservation is all about.  Keep them working as nature intended, avoiding the expense and risks of drug therapy.

So I was excited to find an article entitled “Effects of exenatide on measures of beta cell function after three years in metformin-treated patients with type 2 diabetes.”  Exenatide is sold in the U.S. as Byetta.  It’s a GLP-1 analogue.  

European researchers studied 36 type 2 diabetics for three years.  All were taking metformin.  Sixteen of them also took exenatide, whereas 20 also took insulin glargine (e.g., Lantus in the U.S.). 

What Did They Find?

Both groups achieved similar levels of blood sugar control after three years.  Exanatide users lost 5.7  kg (12.5 lb) while glargine users gained 2.1 kg (4.6 lb). 

After three years of drug use, the subjects were told to stop exenatide and glargine while continuing metformin. After four weeks off-drug:

  • insulin sensitivity improved significantly in the exenatide group while glargine had no effect
  • first-phase insulin secretion improved by a small amount in the exenatide group

However, 12 weeks after stopping the study drugs, hemoglobin A1c and fasting blood sugars returned to pretreatment levels in both groups.  (Hemoglobin A1c is a blood test of overall diabetes control over the preceeding three months.)   

Final Thoughts

You have to wonder if the improved insulin sensitivity in the exenatide group simply reflects their weight loss as compared to the weight gain in the insulin glargine group.  Improved insulin sensitivity is good, any way you can get it. 

ResearchBlogging.orgWhen measured 12 weeks after stopping the study drugs, hemoglobin A1c and fasting blood sugar levels were no better than baseline levels three years earlier.  Very disappointing.  If exanatide or glargine preserved beta cell function, you’d want to see better post-treatment numbers.  The search for beta cell preservation continues.

Steve Parker, M.D.

Reference: Bunck, M., Corner, A., Eliasson, B., Heine, R., Shaginian, R., Taskinen, M., Smith, U., Yki-Jarvinen, H., & Diamant, M. (2011). Effects of Exenatide on Measures of Beta-Cell Function After 3 Years in Metformin-Treated Patients With Type 2 Diabetes Diabetes Care, 34 (9), 2041-2047 DOI: 10.2337/dc11-0291

PS: In case it matters to you, this study was funded at least partially by Amylin Pharmaceuticals and Eli Lilly and Company.

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Which Drug Is Best for Treatment of Type 2 Diabetes?

Physicians now have an amazing array of drug therapies  for control of type 2 diabetes.  Until now, there has been no consensus as to which drugs to use, and when.

The American Association of Clinical Endocrinologists and the American College of Endocrinology have just issued a joint statement with specific drug recommendations.  Their algorithm is quite detailed.  Here are a few highlights you might not know about:

  • Regular human insulin is not recommended
  • NPH insulin is not recommended
  • The following should be used earlier and more frequently:  GLP-1 agonists (exenatide) and DPP-4 inhibitors (sitagliptin and saxagliptin)
  • sulfonylureas are a lower priority
  • metformin is still a key drug

In the U.S., exenatide is sold as Byetta; sitagliptin is Januvia; saxagliptin is Onglyza; metformin is Glucophage (among others). 

If you have type 2 diabetes and are arguing with your physician about optimal drug therapy, this treatment algorithm may be a helpful tie-breaker. 

Steve Parker, M.D.

Reference:  Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: An algorithm for glycemic controlEndocrine Practice, 15 (2009): 540-559.


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