You’ve been following the meteoric rise of GLP-1 receptor agonist drugs and are considering speaking with your healthcare provider about getting a prescription for one. But with so many options on the market, you’re not entirely sure which medication might be the right fit for your needs. While your doctor will be the number one best resource in determining an appropriate treatment plan for your health goals, it’s always a good idea to arrive at your appointment well-prepared.

Many patients are interested in trying Mounjaro, one of the newest, most innovative, and effective injectable antidiabetic drugs currently available. Likewise, there is also a lot of curiosity about Rybelsus—the only oral GLP-1 drug on the market today. Both drugs are approved for the treatment of Type 2 Diabetes in adults, but there are some significant differences between them.

In this post, we’ve provided a direct comparison of Rybelsus and Mounjaro to familiarize you with them. We’ve looked at their mechanisms of action, dosage and administration, side effects, overall efficacy for diabetes and weight loss, and more. For further information and to learn more about which drug (if either) might be the right fit for your needs, speak directly with your doctor or healthcare provider.

Key Differences

  • Rybelsus (semaglutide) is a daily oral medication manufactured by Novo Nordisk. Mounjaro (tirzepatide) is a once-weekly injectable medication manufactured by Eli Lilly.
  • Rybelsus mimics the gut hormone GLP-1 and is classed as a GLP-1 receptor agonist drug. Mounjaro mimics the gut hormones GLP-1 and GIP. It is classed as a dual GLP-1/GIP receptor agonist drug.
  • Research suggests that Rybelsus, though effective for Type 2 Diabetes management, is overall less effective at lowering HbA1c levels than Mounjaro.
  • At Mounjaro’s higher doses, the drug is associated with significant weight loss and has been approved under the brand name Zepbound specifically for this purpose. Though clinical research supports the possibility that Rybelsus might also contribute to substantial weight loss at higher doses, the weight loss associated with the drug at its current available doses is comparatively modest.
  • It is possible to switch from Mounjaro to Rybelsus (or vice versa), but switching medications should only be done under the direct guidance of a healthcare professional.
  • Speak with your doctor or healthcare provider to determine whether Rybelsus or Mounjaro may be the right medication for your specific needs and circumstances.

What Is Rybelsus?

Rybelsus (active ingredient semaglutide) is a brand-name, prescription medication manufactured by Novo Nordisk. Approved by the FDA for the treatment of Type 2 Diabetes in adults, it comes in oral tablet form and is taken once daily before breakfast.

Other medications containing the active ingredient semaglutide include:

  • Ozempic—an injectable drug approved for the treatment of Type 2 Diabetes in adults as well as the reduction of risks associated with related cardiovascular disease.
  • Wegovy—an injectable drug approved for weight loss and chronic weight management in overweight and obese populations.

See also: Wegovy vs Mounjaro

What Is Mounjaro?

Mounjaro (active ingredient tirzepatide) is a brand-name, prescription medication manufactured by Eli Lilly. Approved by the FDA for the treatment of Type 2 Diabetes in adults, it is injected subcutaneously once weekly.

Other medications containing the active ingredient tirzepatide include:

  • Zepbound—an injectable drug with a composition identical to Mounjaro’s that is approved for weight loss and chronic weight management in overweight and obese populations.

How Rybelsus and Mounjaro Work

Rybelsus and Mounjaro are both GLP-1 receptor agonists. However, Mounjaro is also a GIP receptor agonist. Let’s take a closer look at what these classifications actually mean and how each drug works in your body:

Semaglutide, Rybelsus’ active ingredient, and tirzepatide, Mounjaro’s active ingredient, both mimic an incretin hormone known as glucagon-like peptide-1 (GLP-1), which is naturally produced in the human gut. In response to the presence of food, it is responsible for triggering a variety of reactions in different body systems that impact blood sugar control, digestion, and appetite.

When semaglutide or tirzepatide bind to GLP-1 receptor sites, the body’s responses include the following:

  • Insulin secretion is triggered in the pancreas, allowing blood glucose to be efficiently taken into the body’s cells and metabolized for energy.
  • Sugars are inhibited from being released by the liver, naturally lowering blood glucose levels.
  • Gastric emptying and digestion are slowed down, promoting feelings of fullness.
  • Appetite centers in the brain are stimulated further reducing hunger and cravings.

Tirzepatide also mimics another incretin hormone known as glucose-dependent insulinotropic polypeptide (GIP). In addition to binding to GLP-1 receptor sites, it also binds to GIP receptor sites, triggering the following responses:

  • An increase in insulin sensitivity, the responsiveness of your body’s cells to insulin and, relatedly, glucose uptake.
  • A reduction in stomach acid, which further slows down digestion and promotes feelings of fullness.

Additionally, tirzepatide impacts the way fat is stored and distributed throughout the body. For more in-depth information about the similarities, differences, and relationship between GLP-1 and GIP hormones, see this article.

Whom Are Rybelsus and Mounjaro Prescribed for?

Rybelsus received FDA approval in 2019 and is indicated for the treatment of Type 2 Diabetes in adults over the age of 18. As a non-insulin, antidiabetic medication it may be prescribed to patients on its own or in combination with insulin or other drugs. Rybelsus is most effective when combined with a healthy diet and regular exercise. It can offer an alternative to injectable medications for patients who are averse to needles.

Mounjaro became FDA-approved in 2022. Like Rybelsus, it is indicated for the treatment of Type 2 Diabetes in adults. In addition, Mounjaro is also associated with substantial weight loss outcomes. Though it is not officially approved for weight loss, it is frequently prescribed off-label for this purpose.

Tirzepatide was FDA-approved in 2023 under the brand name Zepbound. Zepbound has an identical composition to Mounjaro and is specifically indicated for weight loss and chronic weight management. It is available to overweight adults (BMI over 27) with at least one weight-related health condition and obese adults (BMI over 30) with or without other weight-related health conditions. Like any prescription medication, Zepbound may also be prescribed off-label to patients outside these parameters if the prescribing doctor believes it will be beneficial to their health.

Are Rybelsus and Mounjaro FDA-Approved?

Yes. Rybelsus and Mounjaro are both FDA-approved. See above for further details.

It is important to bear in mind that, just because the FDA has deemed these drugs safe under specific circumstances, does not mean that they are harmless. Speak with your doctor to determine if either of these drugs may be the right fit for your particular needs and health goals.

See also: Rybelsus vs Ozempic

Rybelsus Vs. Mounjaro: Dosage and Administration

Dosage and administration are two areas where Rybelsus and Mounjaro are quite distinct from one another. Let’s take a closer look:

Rybelsus Dosage and Administration

Rybelsus comes in tablet form and is taken once daily. It is normally swallowed with no more than 4 oz. of water on an empty stomach, half an hour before breakfast or any other medications. Rybelsus should be stored at room temperature in its original container and kept separate from any other pills you may take (it should never be added to a pill organizer).

Rybelsus comes in three different doses:

  • 3 mg
  • 7 mg
  • 14 mg

It is standard for patients to begin taking Rybelsus at a starting dose of 3 mg for one month before increasing the daily dose to 7 mg. This allows the body time to adjust to the drug and may reduce the severity of potential side effects.

Some patients remain on the 7 mg dose over the long term, while others may increase to the 14 mg maintenance dose under the supervision of their doctor after another month (or more) has passed. Always follow the dosing schedule recommended by your doctor or healthcare provider.

Mounjaro Dosage and Administration

Mounjaro comes in single-use pens and is injected once per week into the fatty layer beneath the skin of the abdomen, thigh, or upper arm. Injection sites should be rotated on a weekly basis to avoid irritation. For more detailed information about injecting Mounjaro, see our post titled “Where and How to Inject Mounjaro.” **Insert link once blog post is published.

Like Rybelsus, Mounjaro is started at a low dose (2.5 mg) that is increased under the supervision of a doctor at four-week intervals until an optimal maintenance dose is reached. The drug comes in six different doses, each of which is distinguished by a specific label color:

  • 2. 5 mg (gray label)
  • 5 mg (purple label)
  • 7.5 mg (green label)
  • 10 mg (pink label)
  • 12.5 mg (blue label)
  • 15 mg (orange label)

Mounjaro should be refrigerated when possible, but can also be stored at room temperature for up to 21 days if necessary. It should be kept in its original carton away from direct light and should never be frozen. Always check your Mounjaro’s expiry date before injecting and perform a visual inspection to ensure the liquid is clear and free of any cloudiness or solid particles.

Rybelsus and Mounjaro Side Effects

Like all medications, Rybelsus and Mounjaro both come with the potential risk of side effects. Below, we’ve provided an overview of the common and serious side effects of each drug. For more detailed information, see the prescribing information for Rybelsus and the prescribing information for Mounjaro.

Rybelsus Side Effects

Common Side Effects

  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Abdominal pain

Serious Side Effects

  • Serious allergic reactions
  • Pancreatitis
  • Acute gallbladder disease
  • Severe hypoglycemia (low blood sugar)
  • Vision changes (diabetic retinopathy)
  • Acute kidney issues

Mounjaro Side Effects

Common Side Effects

  • Nausea
  • Vomiting
  • Decreased appetite
  • Abdominal pain
  • Diarrhea
  • Constipation
  • Injection site reactions

Serious Side Effects

  • Serious allergic reactions
  • Severe hypoglycemia (low blood sugar)
  • Vision changes (diabetic retinopathy)
  • Acute kidney, gallbladder, or pancreatic issues

As you can see, there is a great deal of overlap between the side effects of Rybelsus and Mounjaro. Considering that the two drugs are both incretin mimetics, this is perhaps unsurprising.

Despite their similar side effect profiles, however, different patients may respond differently to Rybelsus vs. Mounjaro. If side effects are impacting your quality of life on one drug, it may be worth switching to the other (or another similar drug) to see if your body tolerates it better.

Rybelsus Vs. Mounjaro: Overall Effectiveness

When you start on a new medication, you want to feel certain that it has the potential to meet your needs and improve your overall health. Let’s take a look at what the data has to say about the overall effectiveness of Rybelsus vs. Mounjaro for both diabetes and weight loss:

Rybelsus Vs. Mounjaro for Diabetes

Rybelsus and Mounjaro are both effective antidiabetic medications that can help adults with Type 2 Diabetes lower and control their blood glucose levels as part of a broader treatment plan. That being said, current data suggests that Mounjaro may reduce HbA1c levels more significantly than Rybelsus.

A 2017 clinical trial found that Rybelsus (oral semaglutide) reduced HbA1c levels by an average of 1.4 percentage points over the course of a 26-week period. In a 2021 study that compared weekly tirzepatide and semaglutide injections in patients with Type 2 Diabetes, Mounjaro (15 mg) was found to reduce HbA1c levels by an average of 2.5 percentage points over the same period

Rybelsus Vs. Mounjaro for Weight Loss

In terms of weight loss, tirzepatide (Mounjaro, Zepbound) has been associated with unprecedented outcomes. Injectable semaglutide (Ozempic, Wegovy) has also been shown to contribute to substantial decreases in weight. When it comes to Rybelsus (oral semaglutide), the weight loss outcomes are more modest.

Patients in a 2022 clinical trial lost up to 16% of their starting body weight over 26 weeks (and up to 20% or more of their starting body weight over 72 weeks) during which they injected 15 mg of tirzepatide once weekly. In contrast, patients in the same 2017 Rybelsus trial referenced above lost an average of just 5% of their starting body weight over the same 26-week period.

A recent study suggests that oral semaglutide may have much more significant weight loss potential at a higher dose of 50 mg per day, but the medication has yet to be approved for weight loss at this dose. More research and data are needed.

Rybelsus and Mounjaro: Warnings and Precautions

Rybelsus and Mounjaro both come with black box warnings about the potential for the development of thyroid C-cell tumors. Neither medication should be taken by patients with a personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia Type 2.

Other warnings and precautions for both medications include:

  • Pregnancy and breastfeeding
  • Type 1 Diabetes
  • Being under the age of 18
  • Having a history of severe digestive problems, diabetic retinopathy, pancreas, kidney, or gallbladder problems

Before starting Rybelsus or Mounjaro it is vital to disclose your complete medical history as well as any and all medications you are currently taking (including over-the-counter drugs and supplements).

Can I Switch From Rybelsus to Mounjaro (or Vice Versa)?

It is possible to switch from Rybelsus to Mounjaro, or vice versa, but changes to medications should only be made under the direct supervision of a doctor. If you are wanting to switch from one drug to another, make an appointment with your healthcare provider.

The Verdict?

To conclude, Rybelsus and Mounjaro are both effective antidiabetic medications that can make a life-changing difference for adults suffering from Type 2 Diabetes. Although Mounjaro is overall more effective at lowering HbA1c levels and promoting weight loss, Rybelsus may also be the right fit, depending on your needs and circumstances. For many patients, Rybelsus is an attractive option specifically because it does not require the self-administration of weekly injections.

Whether you’re seeking to order Rybelsus, Ozempic, or Mounjaro, can help. We specialize in shipping high-quality Canadian medication directly to your door. Call us today to place your order!

About the Author

Ida Edlweiss Gumpal is a licensed Pharmacist and medical writer. She took her internships at Mercury Drug Corporation, Inc., a Hospital internship at De Vera Medical Center, Inc., and a Manufacturing internship at Philmed Laboratories, Inc. She has plans on attending medical school with the goal of specializing in Neurosurgery or Cardiothoracic surgery.