Mounjaro vs Rybelsus for Weight Loss

Trizepatide (Mounjaro) and oral semaglutide (Rybelsus) are two new medications that have shown great promise in managing obesity in both diabetic and non-diabetic patients. While they have some similarities, they also have important differences that patients and healthcare providers should be aware of. In this blog post, we'll compare and contrast Trizepatide and oral semaglutide to help you better understand these medications.

April 21, 2023

Mechanism of Action

Mounjaro (Trizepatide) and Rybelsus (oral semaglutide) both work by targeting hormones that regulate appetite and satiety. Mounjaro is a dual GIP and GLP-1 receptor agonist, which means that it targets two different hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). These hormones play a role in regulating blood sugar levels and appetite. Rybelsus, on the other hand, is a GLP-1 receptor agonist, which means that it mimics the effects of GLP-1 in the body. GLP-1 helps regulate blood sugar levels and reduces appetite by slowing down the movement of food through the stomach.

Dosage and Administration

Mounjaro is a once-weekly pen injection that is usually started at a low dose by your prescriber, usually 2.5mg, then gradually increases based on whether or not you notice an effect. Rybelsus is an oral tablet that is taken once a day on an empty stomach with a small sip of plain water. It is usually started at a lower dose and then increased gradually in a similar manner to Mounjaro. 


Though both medications have not been approved for use in the management of obesity, they both show promise in weight loss. 

For Mounjaro, the SURMOUNT-1 trial published in 2022 was a large phase 3 clinical trial with over 2500 participants that looked at how effective Mounjaro (trizepatide) 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. 

Though there are no current trials examining Rybelsus in managing obesity, there are studies in diabetic patients that show its effect on weight loss. The PIONEER-1 trial was a phase 3 randomized control trial published in 2019 that examined how well Rybelsus managed diabetes in type 2 diabetics compared to a placebo (2). Rybelsus was given to participants for a period of 26 weeks at different doses.

They found that there was a significant difference in body weight in the treatment group receiving a 14 mg dosage of Rybelsus. This group experienced a 2.6 kg (~5lb) difference after just 26 weeks. It should also be noted that the treatment group was not on a diet plan, exercising around 150 minutes per week, nor were they followed by a dietician. This may tell us that\ there may be an even more significant effect of Rybelsus in combination with diet and exercise for a period of time similar to the SURMOUNT trial. It might even be just as effective! 

Side Effects

Since both medications function similarly, they both share common side effects, 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. However, current studies suggest that these side effects are less common for people taking Rybelsus. 

Cost and Coverage

A major advantage of oral medications is that they cost a lot less than injectable medications. A month's supply of Rybelsus can cost around $950, while Mounjaro may cost over $1000. Some insurance plans may cover both of these medications. However, the FDA has not yet approved them for weight loss alone (this may change in the near future). This may make finding coverage difficult. There are also coupons available that may help with the costs. 


In summary, Mounjaro and Rybelsus are two new medications that can help manage obesity. While they both target hormones that regulate appetite and satiety, they differ in their mechanism of action, dosage and administration, effectiveness, side effects, 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 Trizepatide or oral semaglutide, 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!


  1. 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.
  2. Aroda VR, Rosenstock J, Terauchi Y, Altuntas Y, Lalic NM, Morales Villegas EC, Jeppesen OK, Christiansen E, Hertz CL, Haluzík M; PIONEER 1 Investigators. PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes. Diabetes Care. 2019 Sep;42(9):1724-1732. doi: 10.2337/dc19-0749. Epub 2019 Jun 11. PMID: 31186300.

Dr. Constantine Joseph Pella, MD

Boston University Medical Center

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