GLP-1 Medications for Weight Loss: Everything You Want to Know
GLP-1 medications are game changers for weight loss. They are so popular that the brand name medications, Wegovy® (semaglutide) and Mounjaro® (tirzepatide), can’t be produced in quantity sufficient to meet demand, and therefore the FDA has put them on their shortage list. This means other companies are allowed to copy the drugs without infringing upon the patents owned by Novo Nordisk and Eli Lilly.
The benefit for patients is that the nonbranded medications are much lower cost than the branded medications. This situation isn’t going to last forever though. When these medications are removed from the FDA shortage list, only the brand name medications will be available.
Read below about how these medications work, weight loss results, possible side effects, whether they might be right for you, and how compounded semaglutide and tirzepatide differ from the branded medications.
How Do GLP-1 Medications Work?
GLP-1 (glucagon-like peptide 1) is an intestinal peptide hormone that is involved with metabolism and control of hunger. It is made by cells in the intestine in response to food in the intestine. GLP-1 causes, among other things, insulin release from the pancreas and decreased hunger and appetite.
The medications work like GLP-1 but they aren’t GLP-1. Semaglutide and tirzepatide are altered forms of GLP-1 that remain active in the body for much longer than GLP-1. When GLP-1 is released from intestinal cells, it only remains active in the body for a couple minutes. The altered forms (semaglutide and tirzepatide) remain in the body for longer than 1 week, enabling weekly dosing.
Both medications bind to the GLP-1 receptor in the body and cause a response like GLP-1. They are called GLP-1 receptor agonists, because they bind to the GLP-1 receptor like GLP-1 does. There are GLP-1 receptors throughout the body, including in the stomach and intestine, pancreas, and brain. Medication binding to the GLP-1 receptor causes insulin release in the pancreas (this is why these medications are good for diabetes), a decrease of appetite and interest of food (binding to receptors in the brain), and a slowing of stomach emptying (binding to receptors in the stomach and/or on nerves).
Interestingly, an important way for how gastric bypass surgery works is thought to be by increasing GLP-1. The GLP-1 medications make patients feel similarly to how gastric bypass makes patients feel, with less hunger, less appetite, and less interest in food.
Tirzepatide, in addition to being a GLP-1 receptor agonist, is also a GIP (glucose-dependent insulinotropic polypeptide) receptor agonist. GIP similarly stimulates insulin release, slows stomach emptying, and decreases hunger and appetite.
How Well Do GLP-1 Medications Work?
The short answer is they work very well. They work better than all other meds for weight loss because they target the normal hormone regulatory pathway for hunger and appetite.
What do the published studies show?
Semaglutide
The seminal study on the safety and efficacy of Wegovy® (branded semaglutide) was published in the New England Journal of Medicine in March 2021. This study, in addition to 3 others, led the FDA to approve Wegovy® for weight loss in June of 2021. The 2021 study reported average weight loss to be 14.9% in 68 weeks. 30% of patients lost 20% or more of their weight.
See the New England Journal study on semaglutide here.
Tirzepatide
The seminal study on the safety and efficacy of Mounjaro® (branded tirzepatide) was published in the New England Journal of Medicine in July 2022. This study, in addition to one other, led the FDA to approve Mounjaro® for weight loss in November 2023. The seminal study reported weight loss to average 15% to 20.9% over 72 weeks depending on the dose used. 36% of patients in the higher dose group lost 25% or more of their weight.
See the New England Journal study on tirzepatide here.
What Are The Side Effects of GLP-1 Medications?
The most common side effects were nausea, vomiting, and constipation. These side effects were found to be transient and mild to moderate in severity.
More serious, but uncommon complications for both medications include gallstones and possibly pancreatitis. Also, these medications may increase the risk for medullary thyroid carcinoma.
Weight Regain
When the medication is stopped, the hunger suppression effect of the medication is lost and weight regain can happen.
Comparison with Weight Loss Surgery
Bariatric surgery, in comparison, results in average weight loss of about 25-30% of weight at 1-2 years. This is greater than the weight loss in the semaglutide and tirzepatide studies above, but not by much. In the tirzepatide study above, 36% of patients in the high dosage group lost 25% or more of their weight.
Are You a Candidate for GLP-1 Medications?
The FDA approved Wegovy® (semaglutide) and Zepbound® (tirzepatide) for use in individuals with BMI of 30 or greater, or with BMI of 27 or higher with weight-related medical issues like hypertension, diabetes, or hyperlipidemia. Insurance companies, at a minimum, use these criteria in deciding coverage.
If patients are paying for semaglutide or tirzepatide out of pocket, and not relying on insurance, doctors can make the decision of whether benefits outweigh risks for each individual patient, and not be held to the guidelines above.
Compounded Semaglutide and Tirzepatide
Because the patent-protected, branded GLP-1 medications (Wegovy® and Zepbound®) are currently on the FDA shortage list, other companies can essentially copy and sell the same medications without violating the patents, which are owned by Novo Nordisk and Eli Lilly, respectively. Semaglutide is the active ingredient in Wegovy® and tirzepatide is the active ingredient in Zepbound®.
Many compounding pharmacies are selling semaglutide and tirzepatide. An important thing to understand is that compounding pharmacies are not nearly as regulated as pharmaceutical companies, so it can’t be taken for granted that the product a compounding pharmacy sells is what they say it is.
Many compounding pharmacies, however, do a great job. They buy pharmaceutical grade active ingredients from FDA registered manufacturing facilities, like the brand name companies do, and perform third party potency and stability testing to prove the quality of their products. With compounding pharmacies like these, you can be assured that you are getting exactly what you should be getting.
Compounded semaglutide and tirzepatide are not FDA approved, and not covered by insurance. With a properly vetted compounding pharmacy, however, you can get quality medication with the same active ingredient at a lower price than you can with the branded medication.
Summary
The GLP-1 medications are game changers for weight loss. They work similarly to how gastric bypass works, and the weight loss results are impressive. Side effects are typically mild and resolve quickly. Semaglutide and tirzepatide are patent-protected medications (owned by Novo Nordisk and Eli Lilly, respectively), but because they have been put on the FDA shortage list, other companies can currently legally sell semaglutide and tirzepatide.
If you are interested in compounded GLP-1 medications, we would recommend prioritizing your choice of provider. A good provider will be knowledgable, take the time to do a proper evaluation, do follow-up, and properly vet the compounding pharmacy that is supplying the medication.
