So You Want to Try a Weight Loss Drug, Now What?

You are reading and hearing about it everywhere… GLP-1 RA medications like Ozempic, Mounjaro, and Wegovy. From celebrities, like Oprah, to your neighbor down the street, it seems people everywhere are trying to get their hands on these weight loss pharmaceuticals.  

Are they really worth all the hype? How do these drugs impact long-term health and weight loss maintenance? Is taking a weight-loss drug “cheating”?  

To start, it is helpful to consider that the human body naturally produces a hormone called glucagon-like peptide 1, GLP-1,  in the intestinal cells when we eat. Hormones are fascinating in that they can communicate to other areas of the body far from where they are initially produced. It is suspected that GLP-1 hormones start to be produced as soon as food leaves the stomach and can signal to areas further in the intestines, pancreas, brain, liver, muscle, kidneys, bone, and heart within seconds to prepare for nutrient absorption (1).

Through this communication, GLP-1 hormones: 

1. Stimulate insulin secretion. Insulin is a powerful hormone produced by your pancreas. It serves to signal to your cells to take glucose from the bloodstream and transport it to be used as fuel for muscles.  
2. Lowers glucagon secretion.Glucagon is another hormone produced by the pancreas. Instead of pulling glucose into cells, glucagon signals the liver to release stored sugars into the bloodstream.  
3. Delays gastric emptying. This means GLP-1 hormones slow how quickly food empties from the stomach into the small intestine and may make you feel full longer.
4. Promotes satiety. The brain plays an integral part of feeling hungry or full. It uses a number of different hormones to assess the nutritional needs of the body (2). Since there are receptors in the brain for GLP-1 hormones, it is suspected that they help to promote satiety directly.  

Additionally, our bodies produce another hormone, gastric inhibitory polypeptide (GIP). GIP also works to increase insulin secretion and reduce gastric acid (3).  

GLP-1 RA medications have been around for a while. In 2005, these medications were introduced as a new treatment option for people with type 2 diabetes to help lower blood sugars. Studies have shown GLP-1 RA medications, like weekly injectable semaglutide, can lower A1c, an indicator of blood sugar control, significantly. A1c’s starting between 8-8.9% were lowered by 1.4-2.1%  (4,5). Excitement grew in the medical community as further studies with GLP-1 medications also resulted in weight loss of 9.3-14.1 pounds over 10 months, and showed a protective cardiovascular benefit to those with diabetes (6). As studies demonstrated numerous possible benefits of these medications, the market has grown and additional GLP-1 RA products have been developed. 

The current list of GLP-1 RA medications approved for treatment of diabetes include:

• Dulaglutide (Trulicity®).
• Exenatide (Byetta®).
• Exenatide extended-release (Bydureon®).
• Liraglutide (Victoza®).
• Lixisenatide (Adlyxin®).
• Semaglutide injection (Ozempic®).
• Semaglutide tablets (Rybelsus®).

There is also a very similar class of medications called a dual GLP-1/GIP RA used for diabetes management. 

This includes:

•  Tirzepatide (Mounjaro®)

While GLP-1 RA drugs have been used in the diabetes community for close to 20 years, they have been used as a weight loss drug for a much shorter period of time. The FDA approved the first GLP-1 RA medication specifically for weight loss in 2021. 

This includes:

• Semaglutide injection (Wegovy®) 

The FDA also approved one medication in the GLP-1 RA and GIP RA group in 2023 for weight management, Tirzepatide injection (Zepbound®). Clinical studies of this medication revealed those taking this medication lost up to 20.9% of their starting body weight, using the highest dose, in about 1.5 years. Of note, lower doses of the medication yielded weight loss, as well, of 15-19% body weight loss ( 7).

As mentioned above, GLP-1 RA drugs offer similar benefits as the mechanisms described above by naturally occurring GLP-1 hormones in the body. The difference being GLP-1 RA means GLP-1 receptor agonist. More simply, these drugs block the natural rapid clearance of GLP-1 hormones by the body so the effects can last longer.

Most of these medications are given via a daily or weekly injection using a special “pen” and needle into the soft tissue of the abdomen, thigh, or upper arm.  

As a registered dietitian and certified diabetes care and education specialist, I have heard from many clients that this is the “miracle” drug they have been waiting for their entire lives. I’ve heard over and over that these medications silence the “food noise” that many people have had for as long as they can remember. They are finally able to stop obsessing about food, lose weight, and lower blood sugars. 

However, there are some significant things to consider before starting this medication.

These medications may have significant adverse effects! To be honest, I can’t think of one client I have worked with that did not experience any side effects. Undesirable side effects that I hear most commonly are nausea, vomiting, diarrhea, constipation, food aversions, changes in taste of foods, and indigestion/heartburn. I have known many clients who start the medications and then elect to discontinue because the chronic nausea or digestive problems really impact their quality of life, ability to focus, social lives, mental health, and/or ability to enjoy food.  

Just like medications for blood pressure, cholesterol, and blood sugar management, it is also important to recognize that these medications are intended to be continued indefinitely. Studies suggest that people who decide to stop taking GLP-1 medications gain ~67% of their lost weight back within 1 year as well as lose cardiovascular benefits noted while taking them (8).

Cost is a big factor for many people considering this class of medications. Many health insurance plans will not cover the cost of these medications unless you have other conditions like diabetes, heart disease, morbid obesity, and high blood pressure. Without health insurance coverage, many people report paying $800-1300/month. Even with health insurance coverage, many people are left paying several hundred dollars per month for GLP-1 RA medications.

There are many people who should not take these medications. Those who are pregnant, lactating, or trying to become pregnant should avoid GLP-1 RAs. These medications may also decrease the effectiveness of oral contraceptives with each increase in dose and this should be discussed in advance with your provider. Additionally, the FDA has not approved GLP-1 RA medications for those with type 1 diabetes or individuals under 18 years old. Lastly, there are numerous more serious complications associated with GLP-1 RA medications including risk of thyroid tumors, severe intestinal paralysis, kidney injury (related to dehydration), pancreatitis, allergic reactions, low blood sugar (if taking other diabetes medications), worsening of diabetic retinopathy, and worsening of depression/possible suicidal ideation (9).

With that being said, being informed about the pros and cons of these medications is key! They are a tool that is available that has clinical research supporting their effectiveness in blood sugar and weight management. 

However, not every tool is right for every individual!  

It is imperative to work with your provider and a registered dietitian if you are considering taking a GLP-1 medication. Because of the possible rapid weight loss and profound change in appetite, individuals deciding to use these medications are at significant nutritional risk.  

With weight loss of any kind, muscle mass is lost. Studies suggest muscle loss can be anywhere from 15-35% of lost weight (10).  Since muscle is the primary driver of how much energy a body requires, loss of muscle mass means significant reduction in food requirements and higher potential for future weight regain. Minimizing muscle loss through optimizing protein intake is essential for healthy metabolism.  Research suggests that 1.5-2 times the RDA for protein is needed for most adults to limit the loss of muscle mass (11) (12) (13). This is about 0.55 g-0.72 g of protein per pound of body weight (or 1.2-1.6 g/kg).  Avoiding excessive protein intake yet meeting needs is essential in this process. A registered dietitian can help you get it right and enjoy the foods you are eating!

GLP-1 RA drugs also increase risk for other nutritional deficiencies because they reduce food intake and may decrease stomach acid production. Stomach acid is our first line defense against food poisoning, bacterial overgrowth, and infection. Low stomach acid inhibits pepsin production which is essential for protein digestion and can cause symptoms of heartburn/indigestion. An acidic environment is also required for the absorption of Vitamin B12, vitamin C, iron, calcium, magnesium, zinc, and copper.  Deficiency of these nutrients can cause weakness, fatigue, poor bone health, and nervous system problems.

Another consideration before starting a GLP-1 RA medication is food history. Many of the clients I work with have experienced body shame and food trauma for their entire lives! If not addressed, using a weight loss drug can further deepen the emotional scars and contribute to disordered eating patterns and significant malnutrition.  

Feeling hunger and satiety cues is a natural way for the body to communicate its needs. I strongly advocate that if you decide you want to try a weight loss medication, you work closely with your provider to use the lowest effective dose. While some GLP-1 RA medications have a wide variety of doses, the gains of higher doses versus additional weight loss are minimal. These higher doses seem to also come with stronger side effects for many. With slow and gradual titration of the medication and working closely with a registered dietitian, we can help to minimize the undesirable side effects of these medications while optimizing nutrition and long-term success! Working with a registered dietitian if you decide to go off a GLP-1 RA medication has also been demonstrated to reduce weight regain significantly (14). 

To summarize, GLP-1 RA medications are certainly a tool that can be helpful for blood sugar management and weight loss. Being informed about how the medication works, possible side effects, your personal health and food history, cost, and long-term goals can help you make a decision if it is right for you. I would strongly recommend that you meet with a registered dietitian if you are thinking about starting, are already on, or if you would like to stop taking a weight loss medication. A registered dietitian on our team will assist you in optimizing your protein and vitamin/mineral needs, enhance your natural GLP-1 production, brainstorm with you to make healthy eating practical for your lifestyle, ensure you are eating foods you love, and be your advocate and partner as you navigate your relationship with food. 

Reach out to us today! 

We would love to hear your story! 

Written by our Registered Dietitian and board certified specialist, Sarah Micallef.