GLP-1 Drugs: What they are and Why They Matter

Background Information

GLP-1 stands for "glucagon like peptide - 1". These are medications that were first discovered in---of all places--- the spit of the Gila Monster--- a lizard from the desert southwest of our nation.

GLP-1: Discovery, Development, and Applications

Glucagon-like peptide-1 (GLP-1) is a type of peptide hormone that was first identified in 1984 when researchers discovered its ability to modulate insulin production in pancreatic islet cells (Drucker DJ, 2006). Interestingly, GLP-1 was later found in the saliva of the Gila monster, a venomous lizard native to the desert southwest of the United States. The saliva contains a substance called exendin-4, which shares structural similarities with GLP-1 and influences insulin production in a similar manner (Eng J, et al., 1992).

In 2005, the first GLP-1 agonist drug called Byetta (generic name exenatide) was approved by the US Food and Drug Administration (FDA) for the treatment of type 2 diabetes (FDA, 2005). Exenatide, derived from the Gila monster's saliva, functions by mimicking the action of GLP-1 and thus helps regulate blood sugar levels. Since then, several other GLP-1 agonist drugs have been approved for the treatment of diabetes.

During clinical trials and post-marketing surveillance, it was observed that many patients taking GLP-1 agonists experienced weight loss. This discovery prompted pharmaceutical companies to investigate the potential use of these drugs for weight management purposes. In 2014, the FDA approved Saxenda (liraglutide) as the first GLP-1 agonist drug specifically for weight loss (FDA, 2014). Later, in 2021, Wegovy (semaglutide) was also approved for the same indication (FDA, 2021).

In conclusion, GLP-1 agonist drugs have emerged as an important class of medications for managing type 2 diabetes and obesity. Their discovery, rooted in the study of an unusual lizard species, highlights the importance of diverse sources of inspiration in the development of novel therapeutics.

References:

• Drucker DJ. (2006). The biology of incretin hormones. Cell Metabolism, 3(3), 153-165.

• Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. (1992). Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem, 267(11), 7402-5.

• FDA. (2005). FDA Approves New Treatment for Diabetes. Retrieved from https://wayback.archive-it.org/7993/20170112222820/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2005/ucm108419.htm

• FDA. (2014). FDA approves weight-management drug Saxenda. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-approves-weight-management-drug-saxenda

• FDA. (2021). FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014

Chemistry

Chemically, GLP-1s are very small protein molecules called "oligo-peptides". They are very fragile molecules that are easily degraded by harsh environments. For example, stomach acid will destroy them and render them ineffective although one GLP-1 called "Rebelsus" has been formulated to protect it from stomach acid and allow it to be used orally.

GLP-1 drugs work by stimulating the release of the hormone called insulin from islet cells in the pancreas. The drugs also slow gastric emptying and reduce appetite.

GLP-1 drugs were first used to treat adult onset  (Type-2) diabetes. Shortly after their initial release for this illness it became apparent that the drugs also caused weight loss in at least some of the people who took it. Today, many years after the first GLP-1 drug was approved, two of them---Wegovy and Saxenda--- are currently approved for weight loss with a third drug, Mounjaro about to be approved.

How Much Weight Loss do GLP-1s Produce?

The weight loss effects of GLP-1 drugs vary from person to person but on average they are reported to produce an average of 13% to 22% weight loss. These are extremely good results and if we take them on face value they argue strongly for the drugs. 

Keep in mind that these numbers come from clinical trials funded and run by the drug companies that make the GLP-1 drugs. Clinical trials tend to be idealized environments and quite often, once medications are used in the real world, the results are not as good. Whether this proves true with GLP-1 drugs remains to be seen. They have not been on the market long enough yet to really judge.

Anecdotally, the patients that I have treated with GLP-1 drugs have done well with one person losing about 20% over six months and several others losing 10-17 percent in the same time span. These are clearly very good results.

How do GLP-1 Drugs Compare to Traditional Weight Loss Drugs?

If we accept the results from drug company clinical trials then GLP-1 drugs do work better than traditional medications like phentermine, phendimetrazine and diethylpropion. 

But how much better are they?

Well, here I do have a massive amount of data accumulated over 32 years of treating people with classic weight loss drugs. If I compare my real world data with Classic weight loss medications against the drug companies' ideal data on GLP-1 drugs, then GLP-1 drugs are more effective by a few percent. My data shows that on average people lose 9-14% on average when treated with classic weight loss drugs while the top 10% of my patients lose 21-29%.

The bottom line is this: GLP-1 drugs appear to work---on average--- slightly better than classic weight loss drugs but more time and experience will be needed to make a better determination.

GLP-1 Drugs Approved for Weight Loss

As I write on the first day of Spring, 2023, there are only two GLP-1 drugs that are specifically approved for the treatment of obesity in the US. They are:

​

1. Saxenda

2. Wegovy

​

A third drug, tirzepatide (current diabetes-approved brand name "Mounjaro") may be approved for weight loss soon.

GLP-1 Drugs Approved for Diabetes

Here are all the GLP-1 drugs currently approved in the US for the treatment of type-2 diabetes. Keep in mind that all of these drugs are known to produce weight loss even though they may not be specifically approved for weight loss.

​

Byetta (exenatide):

Byetta is a short-acting GLP-1 receptor agonist that is injected twice daily before meals to help control blood sugar levels.

Bydureon (exenatide extended-release):

Bydureon is a long-acting version of exenatide, which is injected once weekly to help control blood sugar levels.

Victoza (liraglutide):

Victoza is a once-daily injectable GLP-1 receptor agonist that helps regulate blood sugar levels. It is the same active ingredient as Saxenda, which is approved for weight management.

Trulicity (dulaglutide):

Trulicity is a once-weekly injectable GLP-1 receptor agonist that helps improve blood sugar control in adults with type 2 diabetes.

Ozempic (semaglutide):

Ozempic is a once-weekly injectable GLP-1 receptor agonist that helps control blood sugar levels in adults with type 2 diabetes.

Rybelsus (oral semaglutide):

Rybelsus is the first oral GLP-1 receptor agonist approved for the treatment of type 2 diabetes. It is taken once daily in tablet form.

Adlyxin (lixisenatide):

Adlyxin is a once-daily injectable GLP-1 receptor agonist that helps improve blood sugar control in adults with type 2 diabetes.

Mounjaro: (Tirzepatide):

Mounjaro is made by the giant drug company called Eli Lilly. This is the drug that seems to produce the most weight loss but it is not yet actually approved for weight loss.

​

These medications are intended to be used in combination with diet and exercise to manage blood sugar levels in individuals with type 2 diabetes. It is essential to consult your healthcare provider before starting any medication for diabetes management, as they can provide personalized advice and guidance based on your specific medical history and needs.