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Pros and Cons of Semaglutide and Tirzepatide for Weight Loss

Tapeworms? Low-dose arsenic? Cigarettes? Fat-reducing soap? These are just a few wacky weight loss fads from our history.  There’s no question that people seem to be obsessed with losing weight. It’s kind of a ‘try now and ask questions later’ type of subject. People want easy, effective strategies where the weight just melts off, and they don’t have to work hard. Interested in learning more? Here are a few Pros and Cons of Semaglutide and Tirzepatide for Weight Loss.

Is Semaglutide FDA Approved?


The latest trend to take hold is glucagon-like peptide-1 (GLP-1) agonist prescription drugs like Ozempic, Wegovy, Mounjaro, and other semaglutide or tirzepatide based drugs. These drugs are used for weight loss but only two are FDA-approved for weight loss – Wegovy and very recently Zepbound. Wegovy is a semaglutide-based medication produced by Novo Nordisk and was approved for weight loss by the FDA on June 4, 2021.

Zepbound is a tirzepatide based peptide medication made by Eli Lilly and was approved by the FDA on November 8, 2023.

The other prescriptions mentioned are FDA-approved for type 2 diabetes. Doctors and researchers saw their diabetes patients losing weight. This led to them prescribing semaglutide drugs like Ozempic off-label for weight loss. These drugs were so popular last year that there were rumors of shortages. “It could take years to fulfill the demand for Ozempic and Wegovy, the CEO of drug manufacturer Novo Nordisk told CNN. The company has restricted the supply of starter doses of Wegovy, the Semaglutide medication specifically approved for weight loss, as it struggles to meet skyrocketing demand.”

As a person involved in the health space, when I first heard about these peptide-based medications, I was concerned, as I have seen trends and medications come and go over the years. At first, all the information I heard was focused on the possible side effects, and then, I listened to the flip side from an integrative doctor whom I respected. She sang of the many benefits beyond weight loss and how these medications/peptides are often misunderstood. This got me listening more and digging for the answers. Are these medications miracle drugs, or are they harmful? As time elapses, the truth will be unveiled. However, as I looked for answers, a few concerns did emerge.

Is Semaglutide Dangerous?


While these medications and peptides can be effective for weight loss, there are 5 main concerns that I see:

  • High out-of-pocket cost and strict parameters for insurance coverage for the medications
  • Reported side effects: Wegovy and Zepbound
  • Potential for muscle loss
  • Weight regain
  • Inconsistent emphasis on and lack of support for permanent behavior changes

In this blog, the latter 3 points will be focused on.

Potential for Muscle Loss on Semaglutide and Tirzepatide

Some physicians are very alarmed at the muscle loss seen by their patients on these medications. Peter Attia, M.D., stated that “almost every patient we put on this drug [semaglutide] has lost muscle mass at a rate that alarms me.”

With Wegovy’s STEP1 clinical trial of 1961 participants over 68 weeks, the primary end point was weight loss, and changes in body composition were NOT evaluated. They should have monitored ALL participants for body composition changes, but unfortunately, they did not. However, data from an exploratory analysis of the STEP1 study consisted of 95 people on Wegovy (semaglutide) and 45 people who received a placebo. The researchers conducted body composition scans (DEXA) on all participants to monitor their body mass. Participants who received the drug lost an average of 19.3% of their fat mass, 27.4% of visceral fat mass, and 9.7% of their lean body mass (muscle). Participants who received a placebo had no significant changes in body composition in 68 weeks.”

What does this mean? People in the STEP1 study (1 year and 4 months) did lose some muscle (9.7%) but overall they also lost 19% of total fat and a significant amount of visceral fat (27%) which is the most dangerous kind of fat because it surrounds internal organs. However, were they able to keep the weight off long-term? Did they lose muscle because of the drugs OR because their diets were too low in calories and protein?

Sarcopenia, age-related muscle loss, is a real problem as we age with about 3-8% muscle loss per decade starting at age 30 and increasing after age 60. (Holloszy JO. The biology of aging. Mayo Clin Proc. 2000;75 (Suppl):S3–S8.) AND (Melton LJ, III, Khosla S, Crowson CS, et al. Epidemiology of sarcopenia. J Am Geriatr Soc. 2000;48:625–630.) Obese individuals are at an even higher risk of sarcopenia.

Are these weight loss patients being made aware of these facts and warned to look out for muscle loss? Are their prescribers regularly monitoring them for muscle loss? Unfortunately, the answer is usually no. I know there are exceptions to this statement, but those physicians are rare.

How Do You Not Lose Muscle On Semaglutide?

As a nutritionist specializing in supporting individuals on semaglutide for weight management, I recommend clients reach out for personalized guidance tailored to their specific needs and health goals. To mitigate muscle loss while on semaglutide, ensuring an adequate intake of calories and protein is crucial. Additionally, incorporating strength training into your routine, ideally 1-2 times per week, can help preserve lean muscle mass. Prioritizing sufficient sleep for 7-9 hours each night is also essential for overall health and muscle recovery.

Contact me today for a personalized diet, menu plans, and further tips on maintaining muscle mass while utilizing semaglutide. I offer comprehensive support and guidance for people while using these medications that they don’t receive from many of their prescribing doctors.

Is There Weight Rebound After Wegovy?

Of the 1961 participants in the STEP 1 semaglutide study, 327 were followed for an additional 52 weeks to see if they regained their lost weight. On average, participants regained two-thirds of the weight they lost. “During 68 weeks of treatment in the STEP 1 trial, people taking semaglutide had lost an average of 17.3% of their body weight, whereas those taking placebo lost just 2.0%. During the 52-week extension phase, after stopping randomized treatments, the average weight regain was 11.6 and 1.9 percentage points in the semaglutide and placebo groups, respectively.”

To put this in perspective, if someone lost 40 pounds in the 68-week study, they regained 26 pounds in the year after discontinuing Wegovy (semaglutide). Therefore, they would be down about 14 pounds after nearly 2.5 years.

What about the cardiovascular benefits seen in participants? Did those benefits last? “Systolic and diastolic blood pressure both returned to baseline values by 52 weeks after treatment withdrawal. But levels of C-reactive protein (an inflammation marker), high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglycerides were still significantly improved in the semaglutide group relative to the placebo group.”

Is There Weight Rebound After Zepbound?

What about Zepbound (tirzepatide)? Did those participants experience weight regain when stopping the medication? Yes, an average of 14% weight regain was seen over the following year.

“After 36 weeks of open-label maximum tolerated dose of tirzepatide (10 or 15 mg), adults (n = 670) with obesity or overweight (without diabetes) experienced a mean weight reduction of 20.9%. From randomization (at week 36), those switched to placebo experienced a 14% weight regain and those continuing tirzepatide experienced an additional 5.5% weight reduction during the 52-week double-blind period.”

What were the conclusions of both studies after the weight regain results were observed? Their only suggestions were to continue using the medications to avoid weight regain.

It’s Not a Diet, It’s a Lifestyle

Final Concern

As you can see by the trial data for WeGovy (semaglutide) and Zepbound (tirzepatide), there does not seem to be an emphasis on permanent lifestyle changes. Although participants in these trials did receive some education on lowering their calories and increasing exercise, their overall solution, which was stated, was to continue drug therapy indefinitely, NOT changing underlying habits. This same sentiment seems to be perpetuated by most doctors prescribing these medications as well. These medications are given so loosely these days that patients are receiving minimal if any, guidance on lifestyle changes necessary to change their health trajectory significantly. They are left to rely on medications for long-term weight loss. Although some are successful with just the medication on board, without proper monitoring, they could be losing too high a percentage of muscle vs. fat. This in turn, could damage their metabolism and make them more likely to regain the weight quickly upon stopping the medication (as often seen with ‘yo-yo dieting.’) In addition, if the underlying behaviors that got them to their overweight or obese state have not been changed. They are more likely to regain weight or rely on the medications long-term.

Some people have no idea how to eat while taking these medications properly. Semaglutide and tirzepatide medications are very effective at suppressing appetite primarily by slowing gut motility. If these people do not prioritize protein in meals, healthy fats, fiber, vitamins, and minerals, they could have many nutrient deficiencies. Also, anyone can ‘eat your way through these medications,’ meaning you can ignore the fullness signals and eat even though you aren’t that hungry. This can happen, especially after someone has been on the medications for a while. You can get to a state of “metabolic adaptation” where you can ignore the satiety signal. Do you think that a person eating this way has earned anything about preventing weight regain?

Here’s a quick story illustrating the ‘lack of support’ point. A friend of mine called her doctor’s office and mentioned wanting to lose weight. Later, she went to her pharmacy to pick up her medications and noticed Wegovy was prescribed but had no previous mention of it to her. She was shocked. She had no instructions, no warning of side effects, and nothing!! She was especially vulnerable, too, because she had a history of bowel adhesions from gastrointestinal surgery. She should have been warned about potential side effects and monitored for issues. However, she had no guidance, counseling, or warnings. This is only one story, but it may be a common scenario.

How Do You Maximize Semaglutide Results?

In a perfect world, every doctor prescribing weight loss medications would counsel their patients on lifestyle changes needed for long-term success (not just say they need to eat less and exercise more) AND monitor their changes in body composition closely while on these medications. However, we know that most conventional doctors do not have the time needed to do this properly. That’s where registered dietitians and nutritionists come in.

We can support doctors and patients to ensure they are monitored and cared for while on these medications. I wish every doctor worked with someone who could help support these patients, but unfortunately, that is not the case, and it never will be. Our medical system is not set up that way.

If you or someone you care about is taking these medications, encourage them to seek support from a nutrition professional familiar with them.

These medications do seem to have beneficial properties IF dosed correctly; however, we are at a point where people will be dependent on them forever because the weight regained will be too high without them. The answer lies in supporting these individuals with a multifaceted monitoring approach and individualized plans. These patients need to know what to eat, how much to eat, whether they are losing muscle and strategies to use when hunger rebounds. An integrative and functional medicine approach is the best of both worlds and could offer solutions.

Contact Ana Coyle For Semaglutide Assisted Meal and Weight Loss Plans

If you are local to Los Angeles or Orange County, I can monitor your weight loss patients with my state-of-the-art body composition monitoring machine by Styku. It’s a 3D infrared camera that accurately measures body composition. If you do not live in the area, I can also work with your patients virtually on the diet and lifestyle changes needed for long-term success, as well as monitor patients for nutrient deficiencies with advanced functional lab testing.

(Ana is a registered dietitian and holistic nutritionist in Los Angeles who supports patients on GLP-1 medications and many others seeking better health through a holistic approach.)

2 Responses

  1. Mrs. Coyle‘s expertise has played a pivotal role in my journey with semaglutide leading to remarkable results. However, what truly sets her apart is her personalized approach tailored specifically to my needs and circumstances. Amidst the challenges of navigating weight loss, exercise, and nutrition during menopause, Mrs. Coyle emerged as a guiding light, providing a consistent feedback. The utilization of regular body scans to titrate, my protein intake, and weight workouts was the game changer. This data driven approach has insured optimal progress towards my goals. I am at my goal weight.

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