While GLP-1 medications may seem relatively “new” since everyone suddenly seems to be talking about them, they are not new. They have been approved for the treatment of diabetes since 2005. The only thing “new” about them is that they are now approved for weight loss, without a diagnosis of diabetes.
So while there are a lot of wild headlines floating out there about these “new” medications, they have quite a long history of safety and effectiveness. Here’s a brief history of GLP-1 agonists, how they were discovered, and what the future may hold.
A History of GLP-1 Medications
Like many other pharmaceuticals, you can’t create a medication for something if you don’t know it exists. The development of GLP-1 medications started with the discovery of gut hormones and their effects on digestion, insulin, and appetite in the early 1900s.
In the 1970s and ‘80s, incretin hormones were discovered. Incretin is a type of hormone that helps regulate blood sugar levels by stimulating insulin. GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) are the most well-known of these hormones.
In the 1980s, GLP-1 was recognized for its role in insulin secretion, inhibiting glucagon release, and slowing gastric emptying. It was understood that if we could harness the power of this hormone in some way, it could significantly help those with diabetes improve their blood sugar.
In the 1990s, synthetic GLP-1 analogs were developed but faced challenges when used as a medication because they were rapidly broken down by other compounds in the body. They needed to last longer to have the desired effect of lowering blood sugar.
The Poisonous Lizard
The next part of the story is a little weird and one of those things that makes you wonder how the initial conversation went about this idea.
The researchers needed the GLP-1 to last longer. So somehow they decided to look to the Gila monster, a poisonous lizard native to the southwestern United States and northern Mexico, for answers. The lizard only eats 3-5 times a year and can naturally manage its blood sugar and glucose levels despite not eating, so researchers wanted to understand why.
Upon studying the lizard, they found a hormone called exendin-4 in the lizard’s saliva. This hormone was particularly intriguing because it shared many similarities with GLP-1 in humans.
However, exendin-4 had an advantage: it was resistant to degradation or breakdown. This allowed it to remain active in the body for a longer period, meaning its effects could be harnessed to help regulate blood sugar and appetite. Somehow the saliva of a Gila monster led to a breakthrough in diabetes treatment. Seriously, who knew?
The First GLP-1 Medications
In 2005, the first FDA-approved GLP-1 medication called Exenatide (Byetta™) hit the market for the treatment of type 2 diabetes. Liraglutide (Victoza™) followed in 2010 but was also only approved for diabetes. Both of these medications have to be injected daily, which could be a barrier for people wanting to use the medication.
From 2014 to 2016, several once-a-week GLP-1 medications were approved for the treatment of diabetes. These included: dulaglutide (Trulicity™), albiglutide (Tanzeum™), and semaglutide (Ozempic™). A once-a-week injection made it a more palatable option for many trying to manage their type 2 diabetes.
Diabetes, Heart Health, and Weight Loss
As patients started to use these medications with success, the body of research on their benefits also continued to grow. By 2016, it started to become apparent that semaglutide had benefits beyond blood sugar control.
Clinical trials were also discovering benefits for heart health, with some trials suggesting it could significantly lower the risk of death from cardiovascular events, as well as the risk of non-fatal heart attacks and strokes.
Diabetes, heart disease, and many other chronic conditions have one underlying common risk factor– obesity. While obesity isn’t the only underlying cause of these conditions, it plays a significant role in increasing the risk of chronic lifestyle-related illness.
In the mid-2010s, clinical trials started to demonstrate that semaglutide was really good at helping people lose weight. Some doctors started using it off-label for weight loss only, even in those without diabetes, and the Ozempic craze was born.
Wegovy™ Hits the Market
The weight loss market is significantly larger than the diabetes market, so it’s no surprise that pharmaceutical companies would jump at the opportunity to target this group with an effective medication.
In 2021, semaglutide received approval for the treatment of chronic weight management under the brand name Wegovy™.
In 2022, Eli Lilly released a new GLP-1 called tirzepatide (Mounjaro™), initially for the treatment of diabetes, but then quickly got it approved in 2023 for weight loss under the name Zepbound™. Tirzepatide seems to be more effective at inducing weight loss than semaglutide as it is a dual-peptide drug, that includes GLP-1 and GIP.
The Future of Diabetes, Obesity, and GLP-1
The bottom line is these medications are not “new”. They have a long history of use for diabetes, even though they have been recently approved for weight loss.
By 2030, it is expected that around 9% of the US population will be using GLP-1 medication due to their effectiveness and benefits. As the research around chronic disease management continues to evolve, GLP-1 medications stand out for their ability to improve metabolic health. but also for their potential to help manage other related conditions.
Future research will continue to explore additional benefits of GLP-1 medications, which could lead to the development of treatments for other conditions. With every new finding, the role of these powerful medications continues to expand, offering hope for patients worldwide.
Stay up to date with the evolving GLP-1 space by listening to the GLP-1 Hub podcast.
