By now it is likely you have heard about a popular class of medications used to treat diabetes and obesity, called Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) as their use has skyrocketed over the past few years. In fact, a recent study focusing on overweight and obese adults (without diabetes) in the United States has indicated a dramatic 700 percent increase in glucagon like peptide-1 receptor agonist (GLP-1RA) treatment initiation from 2019 to 2023 alone. An additional survey shows at least 13% of American adults have tried a GLP-1 agonist for weight loss, to treat diabetes, or to reduce the risk heart disease.
With the outpour of promising information, news and statistics that have become available in the last few years, it is not surprising you may be curious about how GLP-1 RAs came about and the options available on the market. Read on to learn more about these medications, the history behind them and a review of which ones are currently available.
How were GLP-1s developed?
The beginnings of GLP-1RA date back to over 100 years ago in the 1900s when European physiologists discovered that there were hormones created in the intestines that influenced metabolism. These hormones, named incretins, play an important role in managing diabetes by triggering the pancreas to release another hormone, insulin, to help control blood sugars.
The two main incretin hormones identified as key to blood sugar, as well as appetite control, are called glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Initial trials of using the naturally produced incretins as medication therapy for type 2 diabetes were unsuccessful since they could not last long enough in the body, so synthetic forms of incretins, namely GLP-1, were developed. Scientists discovered that the saliva of a large lizard called the Gila monster, contained a more stable form of GLP-1 which they named exendin-4.
The development of the medication Exenatide followed which was the very first GLP-1RA approved in 2005 for treatment of type 2 diabetes in adults, as an injection given twice daily. Since then, other GLP-1 RA for the treatment of type 2 diabetes have been developed, including longer acting formulations which can be given weekly instead of daily. An oral pill form has also been created.
The potential for GLP-1RAs to help with weight loss while used for diabetes, led to research trialing these medications for weight management at doses higher than those used for diabetes treatment. In 2014, Saxenda was approved as the first daily injectable GLP-1RA to treat obesity and soon others followed, including longer acting varieties dosed weekly.
Which GLP-1s Are Currently Available on the Market?
Since the first GLP-1RA was approved nearly twenty years ago for the treatment of type 2 diabetes in 2005, many additional ones have been developed and come to market, some of which are also indicated for weight management. All the GLP-1 RAs are indicated for use along with diet and exercise to maximize their benefits.
Diabetes Treatment
- Exenatide (brand name: Byetta)- the first GLP-1 RA approved by the FDA in 2005 to treat type 2 diabetes and is an injection that is given twice per day.
- Liraglutide (brand name: Victoza)- the second GLP-1 RA to come to market in 2010, also indicated for type 2 diabetes and needs to be injected once daily. Victoza has also been approved for adults and children aged ten and older with type 2 diabetes.
- Exenatide extended release (brand name: Bydureon)- approved in 2014 and indicated for type 2 diabetes, this GLP-1 RA is an extended-release form of exenatide therefore it only requires an injection once per week.
- Dulaglutide (brand name: Trulicity)- another long acting GLP-1 RA injected weekly and approved in 2014 for type 2 diabetes in adults and later approved for use in children 10 and older with type 2 diabetes . In 2020 Trulicity was additionally approved to reduce risk of major cardiovascular (CV) events (such as CV death, nonfatal MI, or nonfatal stroke) in adults with type 2 diabetes who have established cardiovascular disease or multiple risk factors for cardiovascular disease.
- Semaglutide (brand name: Ozempic)-the third once weekly GLP-1 RA injection to be approved for type 2 diabetes in 2017. In 2020 Ozempic was also approved for a cardiovascular indication – to reduce the risk of major adverse cardiovascular events, such as heart attack, stroke, or death in adults with type 2 diabetes and known heart disease.
- Semaglutide oral tablets (brand name Rybelsus)- this is a once-daily pill form of semaglutide approved in 2019 for the treatment of adults with type 2 diabetes.
Weight Loss Treatment
- Liraglutide (brand name Saxenda)- weight loss was observed when using GLP-1 RAs to treat diabetes, so this led to the development of higher doses for the management of obesity. In 2014 Saxenda was the first GLP-1 RA approved for adults with a body mass index (BMI) of 30 or higher, or for adults with a BMI of 27 or higher plus at least 1 other weight related medical condition such as type 2 diabetes, high blood pressure, or high cholesterol. It has also been approved for weight management in adolescents who are obese (BMI of 30 or more) and weigh more than 60 kg. Just like the diabetes medication Victoza (which also contains the compound liraglutide), Saxenda is also given by injection once daily.
- Semaglutide (brand name: Wegovy)- In 2021 the FDA approved the higher dose of semagltuide (the compound originally used for type 2 diabetes as Ozempic) for obesity treatment. This medication is injected once weekly and is indicated for use in adults with a body mass index (BMI) of 30 or higher, or for adults with a BMI of 27 or higher plus at least 1 other weight related medical condition such as type 2 diabetes, high blood pressure, or high cholesterol. It has also been approved to for weight management in adolescents12 or older with a BMI at or above the 95th percentile for sex and age. WeGovy also received approval recently for cardiovascular risk reduction in adults to reduce the risk of stroke, heart attack, and cardiovascular death in adults with obesity or overweight and heart disease.
Dual GLP-1RA/GIP Receptor Agonists
A newer class of medications has been developed that not only mimics GLP-1 but an additional incretin hormone glucose-dependent insulinotropic polypeptide (GIP), so it is referred to as a “twincretin” or “dual GIP/GLP-1 agonist”. It has a combination effect of simultaneously copying the functions of both these incretin hormones. By mimicking both GLP-1 and GIP, these medications have similar effects on blood sugar, and weight to GLP-1RA, however recent research points to the potential for greater total weight loss when using tirazapetide in comparison to semaglutide.
- Tirzepatide (brand name Mounjaro)- this is a once weekly injection for adults with type 2 diabetes that was approved in 2022.
- Tirzepatide (brand name Zepbound)- this higher dose of tirazepatide via weekly injection was approved use in 2023 for adults with a body mass index (BMI) of 30 or higher, or for adults with a BMI of 27 or higher plus at least 1 other weight related medical condition such as type 2 diabetes , high blood pressure, or high cholesterol.
- Mounjaro and Zepbound are only approved for use in adults and do not yet have cardiovascular indications.
After learning more about GLP-1 RAs, you may have additional questions and interest as to whether these medications would be a new treatment possibility if you have diabetes, are overweight or obese. Making an appointment to discuss medication options with your healthcare team can be an important next step.