Talk about hype! They’ve been called “game-changing,” “the cure for obesity,” and were named “The 2023 Breakthrough of the Year” by the American Association for the Advancement of Science (AAAS).  They are a class of medications, originally developed to help control diabetes, categorized as GLP-1 receptor agonists (or GLP-1 agonists). Almost as soon as they were approved for weight loss they were in short supply, despite an extremely high price tag.  Can they possibly live up to all the excitement?  Are they safe? Are they covered by insurance? Who should be taking them? Who shouldn’t? Why are they so expensive? 

We’ve read the studies and talked with the experts.  Here’s what you need to know: 

What Makes these Drugs Game-Changing? 

For one thing, they work! People who take GLP-1 receptor agonists lose weight – as much as 15-25% of their bodyweight during the first year. Since they were initially developed for diabetics, the medications’ ability to lower an individual’s A1C levels, means that they can decrease or reverse some of the biggest health risks associated with overweight and obesity – those caused by type 2 diabetes. 

Overweight and obesity are associated with a higher risk for many diseases including heart disease, stroke, osteoarthritis, and several types of cancer. When you lose weight, you lower your risk of developing these diseases. But research shows that GLP-1 agonists may also have disease fighting properties in their own right, outside the weight-loss benefits.  The FDA has already approved some of these medications for patients at risk for heart disease. It is likely that we will see other uses and approvals for these drugs. That makes them pretty extraordinary.  

How Do They Work? 

It’s all about hormones!  GLP-1 agonists make us feel like we’ve just eaten even when we haven’t.  Semaglutide drugs, like OzempicÔ and WegovyÔ and liraglutide drugs like VictozaÔ and SaxendaÔ, do this by mimicking the action of one of our satiety hormones called glucagon-like peptide 1 (GLP-1). They slow the movement of food from the stomach into the small intestine. As a result, you feel full faster and longer, so you eat less.  

Other GLP-1 agonists, tirzepatides, like MounjaroÔ and ZepboundÔ trigger an additional satiety hormone, called GIP. This is why those drugs can yield more weight loss than semaglutides. There are more GLP-1 agonist medications in the pipeline that may target additional satiety hormones. 

GLP-1 agonists also help trigger the production of more insulin. Generally, when we eat our blood sugar levels start to rise, and our bodies produce insulin to help lower those blood sugar levels.  Diabetics as well as many obese and overweight individuals, have something known as insulin resistance. It means the body does react properly to the ingestion of food and becomes unable to produce the appropriate amount of insulin in response. GLP-1 agonists help our bodies reset our leptin and insulin responses, which is why they work so well to help diabetics lower their A1C levels.  

Research has found that some drugs in these groups may lower the risk of heart disease, such as heart failure, stroke, and kidney disease. People taking these drugs have seen their blood pressure and cholesterol levels improve even before they have lost a significant amount of weight. This is because GLP-1 agonists appear to have anti-inflammatory properties.  Many diseases are caused or exacerbated by inflammation. And carrying extra weight causes a chronic low level of inflammation. GLP-1 agonists reduce inflammation on their own and further reduce inflammation by causing weight loss. 

What’s the Downside? 

To date the most effective GLP-1 agonists involve a weekly self-administered injection, and there are many people who find that off-putting. The branded drugs come in pre-filled injection “pens” with thin, short needles, that allow patients to click through to the correct dose. The less expensive, compounded GLP-1 agonists require patients to correctly fill a syringe to the correct dose. That has resulted in some confusion and overdosing. Oral versions on the market are not nearly as effective.  More are in the works, but for now injections are the most effective way to take these. 

As with any medication, GLP-1 agonists come with the risk of side effects, some serious. The most common side effects of GLP-1 agonists usually improve after you’ve taken the medication for a while, but most patients do initially report some kind of gastrointestinal side effects, including nausea, diarrhea, constipation and/or vomiting. 

Low blood sugar (hypoglycemia) is a more serious risk linked to this class of medications. But the risk of low blood sugar levels is much higher if you’re taking another medication known to lower blood sugar at the same time, such as sulfonylureas or insulin. 

Another issue with GLP-1 agonists has to do with medical procedures. Patients who will be going under general anesthesia are given preoperative fasting guidelines before surgery. Presurgical fasting significantly reduces residual gastric content (RGC), so that the stomach is fairly empty before surgery.  This is very important so that patients do not aspirate during surgery.  Since GLP-1 agonists slow gastric emptying, patients taking them may have RGC even after 12 hours of fasting, putting them at greater risk of aspiration during surgery. Patients are asked to stop taking this class of medications at least two weeks before elective surgery. But those taking GLP-1 agonists may be at increased risk during emergency surgery. 

Finally, it is pretty clear that this class of medication may have to be a lifelong commitment, and patients should understand this from the start. Virtually all studies show that patients gain some, or most of the weight back in the year after discontinuing the medication. Since these drugs are fairly new, not much is known about the consequences of long-term use. While there is no indication that they pose serious problems, you should know going in that you are probably in it for the long haul. 

Who Should Be Taking GLP-1 Agonists? 

These drugs are expensive, in short supply and require commitment. They are not designed for people who want to lose those 10-20 extra pounds. Remember they were invented for diabetics, who have the greatest risk of suffering health consequences from a lot of excess weight.  

Amaze medical provider, Julia Ball, is one of our in-house experts on these medications. We asked her who should and shouldn’t be taking them. 

“Patients who are candidates for GLP-1 agonist medications typically include individuals with type 2 diabetes who have not achieved glycemic control with other oral medications or insulin. Additionally, patients who are overweight or obese, especially those at risk for cardiovascular disease may also be candidates for GLP-1 agonist medications.  

Our team of healthcare providers here at Amaze are trained to carefully evaluate each patient’s medical history and individual risk factors before prescribing GLP-1 agonists to ensure safety and efficacy.” 

Julia also explained that you may not be a candidate for treatment with a GLP-1 agonist if you have the following:  

1. History of hypersensitivity or severe allergic reactions to GLP-1 agonists or any of the components in the medication.
2. Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
3. Severe gastrointestinal disease, such as gastroparesis or inflammatory bowel disease, as GLP-1 agonists can exacerbate these conditions.
4. History of pancreatitis or a high risk of pancreatitis.
5. Severe renal impairment or end-stage renal disease.
6. Pregnancy or breastfeeding, as the safety of GLP-1 agonists in pregnant or lactating women has not been established.

Why are GLP-1 Agonists So Expensive? 

The pharmaceutical companies, who are setting these high prices, will tell you they have factored in development costs, approval costs, manufacturing costs and the cost to protect their patents.  

These drugs belong to a class of medications known as “biologics,” which are more complex and costly to produce than traditional drugs.  

As we’ve seen, companies need to get FDA approval for each use case for these drugs.  Even though some doctors were using these diabetes medications “off book” for weight loss, they didn’t go mainstream until they were tested and reformulated at a higher dosage and approved for weight loss. 

​Another reason for the high cost of GLP-1 agonists is the active patent protection granted by the government. Patents are legal instruments designed to promote innovation by giving pharmaceutical companies exclusive rights to sell their drugs without competition for a specified period (usually 17 and a half years). This exclusivity allows companies to recoup their research and development (R&D) investments and generate profit. But it costs money to go through the patent process, and companies will cite that as a reason for setting high prices. 

The fact is that pharmaceutical companies set a pricing strategy that focuses on maximizing profit from a smaller patient population rather than pursuing a lower profit margin across a larger customer base. Once the pharmaceutical companies got these drugs approved for weight loss the idea of serving a small patient population became ridiculous in the face of a global obesity epidemic. Sadly, this is where the law of supply and demand kicked in. When there is high demand for a product, sellers raise their prices. While the ethics of this approach may be debated in this case, as long as the patents remain active, these companies have the legal right to set prices as they see fit. 

As competitors hit the market, increasing supply, we can expect to see prices stabilize at lower levels. But that doesn’t help patients who need the medication now.

Are They Covered by Insurance? 

Insurance companies don’t generally like to make it easy for patients to get coverage for very high-priced medications.  They often like to keep a little lag time between FDA approvals for certain use cases and fully covering those use cases. So, it is easy to understand why many insurance plans cover GLP-1 agonists for diabetes but not for weight loss.  

Patients can get around this with prior authorization efforts, where a medical provider files paperwork saying a medication is essential for a patient’s health. Like the price structure, we will likely see more and more plans (and even Medicare and Medicaid) covering these drugs.  But progress is likely to come slowly. 

There is an irony to the low coverage rates. Since overweight and obesity are linked to high-risk for many diseases, covering widespread weight-loss efforts could very well reduce insurance costs in the long-term. It will be interesting to see how long it takes for insurance companies to recognize this. 

What About Less Expensive Options? 

Once the demand for GLP-1 agonists began to surge, it didn’t take long for specialty pharmacies to see an opportunity.  Some specialized pharmacies offer compounded versions of GLP-1 agonists. These custom-made meds combine the active ingredients of the brand-name semaglutides, liraglutides and tirzepatides, with other ingredients so they don’t violate patents.  

You can now find these compounded medications advertised everywhere. Some will be safe and effective. Some will not. This is because compounding is not regulated the way branded pharmaceuticals are. Most sites that offer compounded GLP-1 agonists will tell you that they have doctors on staff who will review your case. This is not the same as having your own medical provider help you review compounded options. 

Greg Jennings leads the Amaze Chronic Care Management team. He is cautiously optimistic about compounded GLP-1 agonists. “Compounding is a very affordable way to get the medications to patients that are either not getting it covered by their insurance or cannot afford the thousands of dollars it costs to get the brand name medication. Researching a reliable and reputable pharmacy that creates the compounds is crucial. Compounding is not FDA regulated, so you want to make sure the company/pharmacy you are using is producing a high-quality product. Our team here at Amaze has done this research and can assist. With that said, the medication does help, but the patient needs to change their approach to food, the mindset around it, recognizing when they are full, and exercising. When all of those things are combined, we see long lasting…sustained…weight loss!”