An NP’s Guide to the Latest Weight Loss Medications

Obesity is a chronic illness that results in increased morbidity and mortality. Its numerous complications range from type 2 diabetes to cardiovascular disease and increased risk of infection. According to the CDC, 41.9 percent of adults in the U.S. are obese. Hence, people have been seeking various methods and medications for weight loss. Treatments that lead to substantial weight reduction can significantly improve outcomes in people living with obesity.

Obesity treatment originally focused on lifestyle-based interventions. However, strict adherence to calorie deficits and increasing physical activity have not proven successful. Since the initial use of bariatric surgery, there has not been much on the forefront regarding obesity treatment. Most recently, it was the ketogenic diet and intermittent fasting.

Now it is a weight loss medication called Semaglutide that has become widely used over the last couple of years. There are four injectable medications that have dominated the spotlight lately: Ozempic, Wegovy, Mounjaro, and now Zepbound. These medications are so popular that pharmacies often run out of stock. They were originally created to help treat type 2 diabetes, but their efficacy on weight loss has pivoted them to be used more broadly for obesity treatment.

What is Semaglutide?

Semaglutide is a glucagon-like peptide 1 (GLP-1) analog originally used to treat patients with type 2 diabetes. It is an injectable medication used once a week under the skin. The FDA originally approved it in 2017 for use in adults with type 2 diabetes. In 2021, it became the first once-weekly medication in its class to be FDA-approved for chronic weight management (under the brand name Wegovy). It works best when used simultaneously with a healthy diet and exercise.

Semaglutide is the generic for Ozempic and Wegovy medications. The same company makes them and have the same ingredients, but Wegovy contains a higher dose. Most health insurances may only cover these medications for type 2 diabetes and not for off-label use of weight loss. Out-of-pocket costs for these medications are $1,000 per month. However, it is common for NPs to complete prior authorization applications to allow coverage of these medications for patients with obesity. If a patient shows failure to lose weight with other methods such as diet and exercise, they may be able to get Semaglutide approved.

These medications have become so popular in the past one to two years that there are often shortages. That means the supply cannot keep up with the demand. As a result of the two factors explained above, many patients are getting Semaglutide through a compound pharmacy.

What is Tirzepatide?

Tirzepatide is the generic for Mounjaro and Zepound. Like Semaglutide, they are GLP-1 once-weekly injections. However, unlike Semaglutide, Tirzepatide also mimics another incretin called glucose-dependent insulinotropic polypeptide (GIP). So, while it has similar effects as Semaglutide, technically, it is the first and only medication in its class. Zepbound was approved for chronic weight management in adults in November 2023.

How Do These Medications Work?

GLP-1 medications mimic a naturally occurring hormone that promotes glycemic control. As these hormone levels rise, they target areas of the brain that help regulate appetite and fullness. GLP-1 medications also slow gastric emptying, which enables patients to feel full faster and longer. They can even help reduce cravings for certain foods, such as sweets or salty snacks. By slowing digestion, they increase the time it takes for food to leave the body. This is pretty similar to the effect of bariatric surgery.

GLP-1 medications are not miracle medications. They should be used in combination with diet and exercise. As patients continue taking these drugs, the body eventually gets used to them, causing weight to plateau. Certain GLP-1 effects, such as slowed gastric emptying, may lessen over time. Once patients stop the medication, they will likely regain the lost weight, as appetite reduction is gone.

One study showed that people who stopped Wegovy regained two-thirds of the weight they had lost. In the study group that stayed on Wegovy, they kept off all of the weight they lost. Thus, many patients plan to take Semaglutide for the rest of their lives. Obesity is a metabolic disease that requires long-term attention.

What Are the Common Side Effects?

Semaglutide and Tirzepatide doses must gradually increase over time to reduce gastrointestinal side effects. Patients will initially start with the lowest dose and continue on the same dose for at least four weeks, allowing their bodies to acclimate to the medication. By the end of the four weeks, the side effects should have started to diminish. Side effects may resume once the patients start taking the next higher dose.

The most common side effects of Semaglutide and Tirzepatide are nausea, vomiting, diarrhea, constipation, abdominal pain, indigestion, gas, acid reflux, fatigue, headache, and dizziness. Most patients will experience at least one of these side effects during the early titration phases of their treatment plan. Some adverse reactions may affect less than 1 percent of people, such as pancreatitis, gallbladder disease, and kidney injury.

Additionally, there is a black box warning about the risk of thyroid C-cell tumors while taking these medications. It should not be taken in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.

There have also been numerous complaints from patients taking these medications regarding their mental health. They allege that Ozempic and Wegovy cause anxiety, depression, and thoughts of suicide. The FDA is currently investigating this. Some patients may not have these adverse reactions with a lower dose of the medication, so they may be able to go back to a lower tolerable dose.

How Much Weight Do People Lose?

Like any type of weight loss method, the amount of weight loss from Semaglutide varies per person. Some patients may start losing weight even at the lowest dose of 0.25 mg, whereas others may not lose any weight until they start taking an optimized dose of 1 mg per week. In a large placebo-controlled trial that lasted 68 weeks, individuals who received Wegovy lost an average of 12.4 percent of their initial body weight compared to individuals who received the placebo.

A large clinical trial demonstrated that people receiving Zepbound lost 15 to 21 percent of their original body weight on average. Some patients who do not find success with Semaglutide may transition to Tirzepatide and have better results. These medications have become popular in women with polycystic ovarian syndrome, who are unable to lose weight using more traditional methods.

Why Are These Medications Controversial?

These medications are controversial because a quarter to one-third of weight loss from these medications is a result of muscle loss. Rapid weight loss from taking Semaglutide or Tirzepatide can lower bone density, decrease the amount of muscle mass, and lower a person’s resting metabolic rate. Studies have illustrated that the ratio of fat-mass loss to lean-mass loss was similar to lifestyle-based and surgical treatments for obesity. Lean muscle mass is important in the body, especially in older adults. So, preserving muscle mass during weight loss is important by focusing on a high-protein diet and weight lifting.

Another controversial aspect of these medications is that those taking it to help manage their type 2 diabetes are often unable to find the drug available at their local pharmacy. Since many people are now using these injections for weight loss, there is often a shortage of the medication. Thus, it makes it difficult for patients using the medication for diabetes to be able to stay compliant with their treatment plan.

The Future of Weight Loss Medications

It has been exciting for both patients and providers to have a new treatment option for obesity. GLP-1 medications such as Semaglutide and Tirzepatide have proven effective in weight loss. However, just like any medication, side effects may occur. NPs should have a thorough discussion with patients to evaluate whether these medications are the right fit for them.

Sophia Khawly, MSN

Sophia Khawly, MSN


Sophia Khawly is a traveling nurse practitioner from Miami, Florida. She has been a nurse for 14 years and has worked in nine different states. She likes to travel in her spare time and has visited over 40 countries.

Being a traveling nurse practitioner allows her to combine her love of learning, travel, and serving others. Learn more about Sophia at