What Are GLP-1 Agonists?
GLP-1 (glucagon-like peptide-1) agonists are a type of medicine for type 2 diabetes that activate GLP-1 receptors in the brain and pancreas. When activated, GLP-1 receptors control blood sugar levels by increasing the production and distribution of insulin.
GLP-1 receptors are usually activated by hormones known as incretins. Incretins are released by the body after food is eaten to control the rise in blood sugar that follows. In people with type 2 diabetes, the effect of incretin is much weaker, and more incretin is needed to keep glucose levels at a healthy level.
GLP-1 agonists solve this problem. Because their chemical structure is almost the same as that of incretins, they can activate the GLP-1 receptor and have the same effects as hormones that are made by the body.
Aside from helping to secrete insulin, GLP-1 agonists control glucose levels by:
- Regulating the production of a hormone called glucagon, which keeps the liver from releasing too much sugar.
- Slowing digestion and thus softening the severity of blood sugar spikes.
- Reducing fat in the liver which is correlated with hyperglycemia.
When paired with diet and exercise, GLP-1 agonists have been shown to be effective for losing weight. A 2018 study found that GLP-1 agonists brought about more weight loss than restricting food alone, and clinical trials have found that patients on GLP-1 agonists can lose as much as 15% of their body weight in a year. Other studies have found that people who are very overweight lose proportionally more weight with GLP-1 agonists.
How Do GLP-1 Agonists Assist in Diabetic Weight Loss?
Although they do not directly burn fat, GLP-1 agonists incentivize eating smaller portions. There are two reasons for this:
- Since they make digestion slower, GLP-1 agonists make you feel full with less food.
- When neurons are activated by GLP-1 agonists, they secrete a protein called leptin, which is responsible for making you feel full.
GLP-1 receptor agonists lower the risk of heart disease, which is closely linked to being overweight. One study found that GLP-1 agonists reduce the risk of nonfatal stroke by 16% and heart failure by 10%. It also found that the risk of cardiovascular death was reduced by 13% and the risk of all-cause mortality dropped by 12%.
Commonly Used GLP-1 Agonists
|Drug||Study Results||Average Weight Loss Per Week|
|Incremental weight loss with all participants; greater weight loss with high BMI participants.||0.23 pounds (6 pounds in 26 weeks)|
(Brands: Byetta, Bydureon)
|Diabetic and nondiabetic participants lost 3 times as much weight as the placebo group.||0.45 pounds (11 pounds in 24 weeks)|
(Brands: Ozempic, WeGovy, Rybelsus)
|The majority of participants lost at least 15% of body weight and one-third lost 20% or more.||0.49 pounds (33 pounds in 68 weeks)|
|Participants taking higher doses lost a greater percentage of body fat.||0.35 pounds (14 pounds in 56 weeks)|
|Participants experienced mild weight loss over a 24 week period.||0.16 pounds (4 pounds in 24 weeks)|
Dulaglutide, which is sold under the brand name Trulicity, is the most commonly prescribed GLP-1 agonist. It is given as a subcutaneous injection once a week.
It’s also prescribed to reduce the risk of life-threatening cardiovascular events (like a heart attack or stroke) in diabetics that suffer from pre-existing cardiovascular conditions.
The most common side effects of Dulaglutide include indigestion, nausea, vomiting, or irregular bowel movements. In rare cases, patients can experience more serious side effects such as pancreatitis, hypoglycemia, or kidney failure. Recent research has suggested that the drug increases the risk of medullary thyroid cancer and multiple endocrine neoplasia.
This agonist is typically prescribed to improve the effectiveness of other medications (notably metformin, sulfonylurea, or pioglitazone).
Exenatide is sold in two forms:
- Byetta is injected twice daily; first within an hour of breakfast and again within an hour of dinner.
- Bydureon is injected once a week.
The most common side effects of exenatide are dizziness, headache, heartburn, diarrhea, burping, and vomiting.
The injected version of semaglutide (sold under the brand names Ozempic and Wegovy) is administered once weekly. In September 2019, a once-a-day pill (Rybelsus) was approved for medical use in the United States, making semaglutide the only GLP-1 agonist that can be administered without any injection. A 2021 study found that semaglutide patients lost 15% of their body weight in 68 weeks.
Aside from digestive side effects (indigestion, nausea, etc.), semaglutide has been linked to allergic reactions, pancreatitis, and kidney problems. In people with heart problems, the medication can cause eye damage.
Known by the brand name Victoza, liraglutide is a GLP-1 agonist injected once a day. Literglutide is prescribed only after primary diabetes medications (like metformin) have proven ineffective.
In addition to gastrointestinal side effects, liraglutide also increases the risk of gallbladder disease, kidney problems, angioedema, pancreatitis, and medullary thyroid cancer.
Sold as Adlyxin in the United States, lixisenatide is injected once daily. It immensely delays the process of digestion and should not be used by patients with gastroparesis. One study found that lixisenatide users lost an average of 4 pounds over 24 weeks.
In 0.1% of cases, patients report an anaphylactic reaction to the medication. Other side effects include nausea, vomiting, and dizziness.