Mechanism of Action
Wegovy and Mounjaro both work by targeting hormones that regulate appetite and satiety. Wegovy is a GLP-1 receptor agonist, which means that it mimics the effects of a hormone called glucagon-like peptide-1 (GLP-1) in the body. GLP-1 stands for glucagon-like peptide-1. It is a hormone that is produced in the intestine and plays a key role in regulating blood sugar levels. GLP-1 is secreted in response to food intake and stimulates the release of insulin from the pancreas, which helps to lower blood sugar levels. It also reduces the secretion of glucagon, which is a hormone that raises blood sugar levels, and slows down gastric emptying, which helps to regulate the absorption of nutrients.
Mounjaro, on the other hand, is a dual GIP and GLP-1 receptor agonist. It works by targeting two different hormones, glucose-dependent insulinotropic polypeptide (GIP) and GLP-1, both of which play a role in regulating blood sugar levels and appetite.
Dosage and Administration
Both medications are administered as once-weekly pen injections for use in weight loss. The starting and maximum doses may be different, but they follow a similar dosing schedule. Your provider will most likely start off at a lower dose at first (usually 0.25 mg for Wegovy and 2.5mg for Mounjaro), then gradually increase depending on whether or not you notice results.
Effectiveness
Both medications have been shown to be very effective at lower body weight along with diet and exercise. The effectiveness of these medications is demonstrated in two major studies that were recently published:
The SURMOUNT-1 trial published in 2022 was a large phase 3 clinical trial with over 2500 participants that looked at how effective Mounjaro (tirzepatide) was at managing obesity (1). Mounjaro was given at different doses for a period of 72 weeks to groups of non-diabetic participants who were struggling with obesity. The participants were also enrolled in a calorie restriction diet (500 kcal/day), did 150 minutes of exercise per week, and had regularly scheduled with a dietician.
They found that after 72 weeks, each group that was taking Mounjaro showed significant weight loss compared to the placebo group. Each treatment group experienced a 15-20% change in weight from the start of the trial, with higher doses showing a greater change. This was compared to the placebo group, which only experienced a 3% change in weight. This showed us that the use of Mounjaro in combination with diet and exercise is very effective at treating obesity.
Next, the STEP 1 Trial was another large randomized control trial with around 1900 participants that examined how effective Wegovy (semaglutide) was at treating obesity in non-diabetic patients (2). Wegovy was given as a once-weekly pen injection starting at a low dose that was gradually increased to a maximum of 2.4mg over a period of 68 weeks. Similar to the SURMOUNT trial, all participants also underwent a calorie restriction diet, exercised for 150 minutes per week, and met regularly with dieticians.
After 68 weeks, they found that participants taking Wegovy experienced a significant reduction in body weight compared to the placebo group. The study also reported that there was an increase in participant-reported physical function after the study, which was not measured in the SURMOUNT trial.
Between the two studies, the mean change in body weight for both studies was the same (~15%); however, more participants achieved at least a 5% reduction in body weight when taking Mounjaro compared to Wegovy based on the data reported in the two trials. In the end, both were very effective at managing weight loss in combination with diet and exercise.
In a study that compared Mounjaro to Ozempic, which is very similar to Wegovy, it was seen that Mounjaro did have a greater reduction in body weight (3). However, it should be noted that Ozempic is given at lower doses than Wegovy, and there are no current trials that directly compare Mounjaro to Wegovy.
Side Effects
The side effects of the medications are very similar, which include multiple gastrointestinal symptoms such as nausea, vomiting, abdominal pain, loss of appetite, and cramps. Typically these symptoms are mild to moderate in severity and go away over time. They also have similar contraindications, such as a history of medullary thyroid cancer, pancreatitis, diabetic retinopathy, etc.
Cost and Coverage
Unfortunately, both Wegovy and Mounjaro are expensive medications. A cost analysis study conducted in 2022 showed that Mounjaro showed a better value for money compared to Wegovy (4). However, it should be noted that both medications can be very expensive, with Mounjaro estimated at $17,000 and Wegovy at $22,000 after 72 weeks of therapy. Some insurance plans may cover these medications to make costs more manageable. However, there is difficulty with Mounjaro since it has not yet been approved by the FDA for use in obesity in non-diabetic patients. This may change in the near future. On the other hand, Wegovy is approved for obesity, which may make finding coverage by insurance more likely.
Conclusion
In summary, Wegovy and Mounjaro are two new medications that have been shown to be effective at managing obesity. While they both target hormones that regulate appetite and satiety, they differ in their mechanism of action, dosage, administration, effectiveness, and cost. Patients and healthcare providers should carefully consider these differences when deciding which medication to use for the treatment of obesity. It's also important to note that these medications should be used in conjunction with lifestyle modifications, such as diet and exercise, for the best results. If you are considering using Wegovy or Mounjaro, talk to your healthcare provider to determine which medication is right for you.
If you would like to learn more about GLP-1 medications or want to see if you might be eligible for medication-assisted weight loss, check out Mochi Health, where board-certified obesity medicine physicians can offer expertise in this realm!
References
- Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4. PMID: 35658024.
- Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10. PMID: 33567185.
- Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25. PMID: 34170647.
- Azuri, J, Hammerman, A, Aboalhasan, E, Sluckis, B, Arbel, R. Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis. Diabetes Obes Metab. 2023; 25( 4): 961- 964. doi:10.1111/dom.14940
