Semaglutide vs. Tirzepatide: What Are the Differences?

You know you’re ready to lose the weight and keep it off. You’ve heard good things about second-generation weight loss drugs (Mounjaro, Ozempic, Wegovy, and Zepbound) and you’re wondering if one of them might be right for you. What’s the difference between Semaglutide (the active ingredient in Ozempic and Wegovy) and Tirzepatide (the active ingredient in Mounjaro and Zepbound)? How do Semaglutide and Tirzepatide work, and are there differences in terms of their efficacy and side effects?

Also, is there another way to lose weight that’s safer, more effective, and more life-transforming than second-generation weight loss medications?

In this article we’ll walk through these questions together.

Semaglutide vs. Tirzepatide: How They Work

What is Semaglutide? What is Tirzepatide? How are they different?

Both Semaglutide and Tirzepatide are in a class of drugs known as incretin mimetics. They are glucagon-like peptide-1 (GLP-1) receptor agonists, which means that they mimic the GLP-1 hormone that our bodies naturally create. When we eat, our intestines naturally secrete GLP-1, which sends signals to our pancreas to produce more insulin. GLP-1 also tells the brain that we are full and slows down intestinal function.

By mimicking GLP-1, both Semaglutide and Tirzepatide tell your body to produce insulin; which is why these medications are effective at treating Type 2 diabetes. They also tell your body that you are full, which is one reason that these medications help you to lose weight.

These medications also work to decrease the amount of sugar produced by your liver, and slow the movement of food through your stomach (called gastric emptying). They thus make you feel full earlier and for longer so that you eat less food.

One key difference is that Tirzepatide works via a second mechanism as well. In addition to mimicking GLP-1, Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. The GIP hormone tells your body to produce insulin and tells your brain that are full just like the GLP-1 hormone does. As a result of this second mechanism, Tirzepatide may turn out to be more effective for weight loss than Semaglutide.

Semaglutide vs. Tirzepatide: Efficacy

What is Semaglutide’s efficacy when it comes to facilitating weight loss? And how does that compare to the efficacy of Tirzepatide?

Both medications are effective at helping many patients to lose weight, and both represent substantial improvements over first-generation weight loss medications such as Contrave®. Possibly because of its dual mechanism, early studies suggest that Tirzepatide may be more effective at helping most people to lose weight. In the STEP-1 trial, Semaglutide patients lost an average of 12.4% more of their body weight than did the placebo group. In the SURMOUNT-1 trial, Tirzepatide patients lost an average of 17.8% more of their body weight than did the placebo group on the maximum dosage.

It’s important to note that for both medications, studies don’t suggest that all patients experience substantial weight loss. In the STEP-1 trial, only about 60% of patients lost 12.4% or more of their weight. In the SURMOUNT-1 trial, only about half of patients lost 17.8% or more of their weight. These medications can be effective, but weight loss varied widely in clinical trials. Being effective in the aggregate does not guarantee that they will be effective for you.

It is also important to note that these are not miracle cures. In the above studies, patients only experienced sustained weight loss by pairing these medications with dietary and exercise changes.

Dosing

Semaglutide and Tirzepatide have different doses. Both are administered once weekly. However, prescriptions for Semaglutide regularly start out at 0.25mg per week, and increase up to a maintenance dose of 2.4mg per week. Prescriptions for Tirzepatide regularly start at 5mg per week and increase up to a maintenance dose of 20mg per week.

Can I switch from Semaglutide to Tirzepatide?

Once patients learn that Tirzepatide may produce more significant and lasting weight loss than Semaglutide, they wonder if they can switch from Semaglutide to Tirzepatide. It is generally safe to switch between name brand drugs, as long as they are prescribed for the same purpose and you’re using them under the direction of a doctor. Because the dosing for Semaglutide and Tirzepatide are different, if you are taking one and decide to switch to the other, make sure to consult your doctor about what your new dose will be. Taking a higher dose than your doctor recommends can lead to serious side effects.

Semaglutide vs. Tirzepatide: Side Effects

The unfortunate truth is that while Semaglutide and Tirzepatide can produce substantial weight loss, and represent strong improvements over earlier weight loss medications, they do carry a serious risk of side effects.

A study of Semaglutide found that almost half (48.6%) of patients reported one or more side effects. The most common side effect was nausea (36.6% of patients) followed by diarrhea (8.6%), fatigue (6.3%), constipation (5.7%), and abdominal pain (5.1%). 8.6% of patients reported moderate symptoms that prevented them from escalating their dose, and 2.9% reported such severe symptoms that they had to stop taking the medication altogether.

The side effects of Tirzepatide are similar but sometimes more prevalent and more severe. In the SURMOUNT-4 trial, fully 81% of Tirzepatide patients reported one or more side effects. Side effects were similar to those caused by Semaglutide, perhaps because of the similarity in how these two drugs work. 35.5% of patients experienced nausea, 21.1% experienced diarrhea, 20.7% experienced constipation, and 16.3% experienced vomiting. 7% reported such severe symptoms that they had to stop taking the medication.

While the known risks of weight loss drugs are generally minor to moderate, patients are also at a higher risk of developing certain endocrine tumors in the pancreas or thyroid glands, as well as pancreatitis and possibly cancer.

Weight regain is also a concern for patients on either medication. Both medications are effective at helping many patients to lose weight, but the weight loss only lasts as long as the patient is taking the medication. When patients stop taking the medication (perhaps due to its substantial costs), they often see the scale creep back up.

Bariatric Surgery: An Alternative Approach to Weight Loss

If you are determined to take either Semaglutide or Tirzepatide, then we can schedule a medical consult to discover which one would be the better option for you and if you are a good candidate.

However, if your goal is to lose weight, keep it off more permanently, and transform your life, then we recommend that you also consider bariatric surgery.

Bariatric surgery is safe and effective. Unlike second-generation weight loss medications, where side effects impact a substantial minority or even majority of patients, at a comprehensive MBSAQIP Center of Excellence in Metabolic and Bariatric Surgery like the Bariatric and Metabolic Center of Colorado (BMCC), the complication rate is very low (under 5%). If a patient does experience any complications, then our double-board-certified bariatric surgeon personally commits to working with them every step of the way in order to get the complication resolved.

Bariatric surgery is also very effective at helping patients to lose weight. Most of our duodenal switch patients lose 90-100% of their excess body weight in the first 9 months and keep it off (read this piece for more about your weight loss surgery options). Imagine how that would feel.

Most of our patients say that the decision to undergo bariatric surgery was the best decision they ever made.

“The best decision I have ever made was to have this surgery. Not only did I improve my health, I have my life back again with my family.”–Georgette Camacho, duodenal switch patient.

Read more bariatric surgery success stories and see the life-changing results of weight loss surgery on patients just like you.

If you’re suffering, don’t wait.  Contact our Denver office today.