Since the FDA approval of Saxenda for weight loss in 2014, a trickle of new medications based on the same drug class, like Wegovy, have followed. What's the difference between them all and which one works best?
All of these medications (Zepbound, Mounjaro, Saxenda, Wegovy and Ozempic) contain a medication in a class of drugs call Glucagon-like peptide 1 receptor agonists (GLP-1 RA for short). The difference is that both Zepbound and Mounjaro contain one additional medication. So we are comparing "single action" medications vs "dual action" medications.
Single Action Medications (GLP-1 RAs)
Wegovy and Ozempic are the same medication (generic name: Semaglutide) and the only difference is the dose that is given and the FDA indication. Saxenda (generic name: Liraglutide) was the first medication in this drug class.
Ozempic: FDA approved for Type 2 Diabetes. Dosing range is 0.25mg once weekly up to a maximum of 2mg per week. Generally, we start low and double the dose every 4 weeks.
Wegovy: FDA approved for Weight Loss. Dosing range is 0.25mg once weekly up to a maximum of 1.7mg to 2.4mg per week. So the dosing is slightly different as we increase this medication and the final dose can be slightly higher.
Saxenda: This was the first medication in this drug class to be approved for Weight Loss in 2014. The generic name is Liraglutide (also marketed under the name Victoza for Type 2 Diabetes). Dosing range is 0.6mg once weekly, up to a maximum dose of 3mg per week. We start low and can increased by 0.6mg every 4 weeks. Because this medication appears to be less effective for weight loss when compared to Semaglutide, we don't see if prescribed as often.
Dual Action Medications (GLP-1 RAs + GIP)
Mounjaro and Zepbound contain a GLP-1 (generic name: tirzepatide) PLUS a second medication in a different class of drugs called Glucose-Dependent Insulinotropic Polypeptide (GIP). Again, the same combination of medications are marketed under two different names based on FDA indication.
Mounjaro: FDA approved for Type 2 Diabetes. Dosing range is 2.5mg once weekly up to a maximum of 15mg per week. Generally, we start low and increase by 2.5mg every 4 weeks.
Zepbound: FDA approved for Weight Loss. Dosing range is 2.5mg once weekly up to a maximum of 15mg per week. Generally, we start low and increase by 2.5mg every 4 weeks.
How do we decide who is eligible for these medications?
The FDA clearly defines who these medications are indicated for (below).
FDA indication: For use as an adjunct to diet and exercise in patients with a BMI ≥30 kg/m2 or patients with a BMI ≥27 kg/m2 and ≥1 weight-associated comorbidity (eg, hypertension, dyslipidemia).
That said, there are also other things to keep in mind, such as any family history of thyroid cancer, personal thyroid nodules, history of gastric bypass surgery, gastroparesis, any history of gallstones or chronic pancreatitis, and how this medication can interact with other medications that you are taking.
The most common side effects are nausea, vomiting, diarrhea and constipation. Less common, but more serious side effects include spontaneous pancreatitis, gallstones and increased risk for thyroid cancer (particularly in patients with a personal or family history of thyroid cancer). I wrote a blog post to quantify this risk that you can read here. The TLDR is that the average risk of thyroid cancer is around 1-2% and GLP-1 RAs appear to increase this risk to around 2-3%. So while the risk is serious, it remains rather low. Whether or not this risk is tolerable for you is personal. My job is to help you understand this risk so that you can make an informed decision.
Okay, but how do they all compare? Which one is best?
I tend to favor Wegovy when prescribing because it tends to cause less side effects when compared to the dual action medications (Mounjaro and Zepbound). While the dual action medications do appear to produce more weight loss, this needs to be weighed against the increased side effects and the risk of clinically significant hypoglycemia (low blood sugar) that can occur on patients both with and without Type 2 Diabetes.
Medication | Trial information | Average weight loss** |
Saxenda | SCALE trial: Saxenda + 500 kcal/day calorie deficit and exercise (>150 minutes/week) over 56 weeks (1) | 1.3% to 14.7% of body weight with an average of14 lbs (6.4 kg) lost. |
Wegovy | Step 1 trial: Semaglutide + 500 kcal/day calorie deficit and exercise (>150 minutes/week) over 68 weeks (2) | 14.85% of body weight with an average of 33.6 lbs (15.3 kg) lost. |
Ozempic (Type 2 Diabetes) | Oral Semaglutide (Rybelsus) versus Ozempic 1 mg weekly versus placebo in patients with Type 2 Diabetes over 26 weeks (7) | Average of up to 15 lbs (6.9 kg) with the maximum dose of Rybelsus compared to 14 lbs (6.4 kg) with a sub-maximal dose of Ozempic. |
Zepbound | Tirzepatide + 500 kcal/day calorie deficit and exercise (>150 minutes/week) over 72 weeks (5) | 16% to 22% of body weight with an average of with an average of 28 lbs (12.8 kg) around week 20. |
Mounjaro (Type 2 Diabetes) | Comparison between Tirzepatide and Semaglutide 1 mg once weekly in patients with Type 2 Diabetes over 40 weeks (6). *We saw more cases of hypoglycemia (clinically low blood sugars) with Tirzepatide and more cases of COVID-19 which is why I strongly suggest vaccination. | 17.6 to 27.28 lbs (7.8 to 12.4 kg) with all doses of Tirzepatide leading to more weight loss compared to Semaglutide 1 mg once weekly. |
Notes about the table above: The Step 8 trial confirmed that Wegovy is more effective when compared to Saxenda which is why we don't hear very much about Saxenda these days (3). The trial evaluating the efficacy of Tirzepatide versus Semaglutide used a comparison dose of Semaglutide that is lower than what is typically used for both Type 2 Diabetes and weight loss (6).
**Percent of body weight loss was used when this data was available.
How long do we use these medications?
Based on the Step 4 trial, when people stoped using Semaglutide (the active ingredient in Wegovy and Ozempic), the weight did come back on (4). That is why dietary transition is so important when using these weight loss medications. If we can use Semaglutide to combat hunger while transitioning to a different way of eating, then it may be possible to achieve our desired weight and potentially maintain it without medication. As always, every body is different and we will do what is best for you.
If you want intensive support and the option of using medication as an adjunct to dietary changes and daily movement, then schedule your first FREE new patient intake today. We'll review your goals, what has and hasn't worked in the past, and come up with a shared plan to get started on making this a reality.
References
*FDA indication and typical dosing was derived from UpToDate.
Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes The SCALE Diabetes Randomized Clinical Trial. Davies et al. Journal of the American Medical Association (JAMA) (2015) https://jamanetwork.com/journals/jama/fullarticle/2428956
Once-Weekly Semaglutide in Adults with Overweight or Obesity. Wilding et al. New England Journal of Medicine (NEJM) (2021) https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without DiabetesThe STEP 8 Randomized Clinical Trial. Rubino et al. Journal of the American Medical Association (JAMA) (2022) https://jamanetwork.com/journals/jama/fullarticle/2787907
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial. Rubino et al. Journal of the American Medical Association (JAMA) (2021) https://jamanetwork.com/journals/jama/fullarticle/2777886
Tirzepatide Once Weekly for the Treatment of Obesity. Jastreboff et al. New England Journal of Medicine (NEJM) (2022) https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. Frías et al. New England Journal of Medicine (NEJM) (2021). https://www.nejm.org/doi/full/10.1056/NEJMoa2107519
Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. Davies et al. Journal of the American Medical Association (JAMA) (2017). https://jamanetwork.com/journals/jama/fullarticle/2657376
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