Weighing in on GLP-1.....Again!

What's the latest on GLP-1 medications

The first time I blogged on the pharmaceutical marvels known as semaglutides (AKA GLP-1s) was June 2023. Ozempic and Wegovy were the two players at that time. Since then, others have followed the leaders—now there’s Mounjaro, Zepbound, and Saxenda. Currently, Wegovy and Zepbound are only approved for obesity (body mass index ≥ 30); with the others you must have a diabetes diagnosis. According to KFF Health Tracking Poll, approximately 6% of US adults (approximately 15 million people) are currently using GLP-1 drugs. 

Let’s review (again) how these drugs work. Semaglutide-based drugs are a class of medications that act similarly to a body hormone called glucagon-like peptide-1 (hence the name, GLP-1). This (incretin) hormone is naturally secreted by the small intestine in response to food ingested. The drugs are commonly referred to as “incretin mimetics” because they mimic the body’s natural hormone. 

When first marketed, the target group was for people with diabetes to help improve blood sugars. In fact, clinical data reports a reduction in HbA1c levels of 1.0-1.8% in patients using GLPs. GLPs work by stimulating the release of insulin in response to an elevated blood sugar after a meal. GLPs also suppress glucagon secretion; glucagon is the body’s hormone that increases blood sugars if your body senses your own blood sugar is running low. By regulating blood sugars for the better, these drugs also indirectly support weight management (for a variety of reasons). 

With each new day, comes new research studies. GLPs have shown promising results in improving liver health, particularly in relation to non-alcoholic fatty liver disease. They also have some potential in reducing alcohol consumption and even potentially treating alcohol use disorder. So stay tuned! 

Back to what these drugs do. Here are some snippets! 

• Hunger Suppression: GLPs help to suppress ones appetite. The brain’s hunger center is located in the hypothalamus. After GLP-1 administration, imaging studies have shown a 40-60% reduction in the receptor sites of the hypothalamus that normally respond to food ingestion. 

• Gastrointestinal (GI) Transit Time: GLPs slow down the transit time of foods traveling through the stomach and into the small intestine. This food journey is typically referred to as “gastric emptying.” They have found that travel time is typically decreased by 30-50% with the use of GLPs. This helps to extend ones satiety (i.e. stomach fullness) level for 4-6 hours after meal ingestion compared to 2-3 hours in untreated individuals. GLPs also Inhibit gastric acid production and secretions, which help in the digestion of food. Also note that many other GI side effects include nausea, diarrhea, vomiting, constipation, bloating, and gas. These all obviously play a role in how much food is desired and/or eaten. Other side effects include pancreatitis, depression, hypoglycemia, headache, fatigue, dizziness, and gallbladder issues.

It’s important to note that everyone has a different experience with these drugs, so side effects don’t apply to all, universally. 

There are many nutrition-related concerns that health care professionals are worried about with these drugs. 

• Muscle Mass Maintenance: Because of the diminished food intake, and for many, a minimal amount of calories eaten, the balance of one’s diet is compromised. Social media posts reinforce the importance of including adequate protein in your meals. Without adequate calories, your body will seek alternative sources of energy stored in your body and that includes muscle mass. You need adequate muscle mass to support a healthy metabolism! 

• Fueling your body: Skipping meals or under eating (because of the feeling of fullness) can easily lead to fatigue, as you may not be eating enough calories to sustain normal body functions. The dramatic weight loss of GLPs is often from calorie deprivation. Many people are exercising along with the medication use, so that requires even more calories need to be eaten.

• More on gut health: Because of the delayed GI emptying, many people complain of constipation. As noted already, biology plays a role in the transit delay with the GLPs but people also don’t take in enough fiber in their diets. The USDA's Dietary Guidelines for Americans suggest 22-28 grams of fiber for women and 28-34 grams for men a day. A general guideline is to consume around 14 grams of fiber for every 1000 calories eaten, but again that’s hard if you don’t feel like eating! With fiber, one must remain well hydrated to form a healthy stool.

Other nutritional deficiencies include calcium, vitamin D and B12, iron, and essential fatty acids. Talk to a registered dietitian to evaluate your intake if you are taking these drugs.

Many insurance companies are covering GLPs (based on diagnosis). But   with a hefty price tag (over $1000/month), many insurers are removing it from their formulary. Check with your individual health insurance plan for your coverage. 

The biggest question I hear is “do I need to be on these drugs for life?” Weight regain after a diet ends is a common occurrence for many people. Statistics demonstrate that more than 50% of individuals get back to their baseline weight by 5 years once they revert to previous lifestyle patterns. We know old habits return! Some scientists believe that your body has a "set point" weight that it tries to maintain; I liken it to a thermostat. When you lose weight, your body may resist further weight loss (the infamous plateau) and may try to return your weight to its biologically set point.

Regarding the GLPs specifically, the STEP 1 trial extension study looked at the changes in body weight and cardio-metabolic risk factors after the medication was stopped. During this 68-week period study, participants received a once-weekly subcutaneous dose of semaglutide along with lifestyle intervention. Researchers found that one year after the cessation  of the GLP-1 shot and the withdrawal of lifestyle intervention, participants regained two-thirds of their prior weight loss, with similar changes in cardio-metabolic variables. The researchers concluded that ongoing treatment is required to maintain improvements in weight and health.

There’s no question that chronic diseases like obesity and diabetes affect health outcomes. And that treating these diseases to promote healthy outcomes is critical. But, anyone going on these drugs needs to understand how they work. I am not advising you what to do, but I encourage you to make an informed decision. Work with your physician to fully understand the course of treatment ahead of you. And team up with a registered dietitian who can address your own personal needs!

In Good Health, 

Sophie