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Mounjaro vs Rybelsus for Weight Loss and Diabetes

Mounjaro vs Rybelsus

Mounjaro vs Rybelsus is a comparison of two potent anti-diabetic drugs: Tirzepatide and Semaglutide 

Mounjaro and Rybelsus are both medications used to treat type 2 diabetes mellitus.

In this article, we will compare the mechanism of action, pharmacokinetics, efficacy, dosage, and side effects of these two medications.


Generic Name


What is Mounjaro?

Mounjaro (Tirzepatide) is a GLP-1 and GIP receptor agonist. It is prescribed for the treatment of type 2 diabetes. The FDA recently approved this drug for use in May 2022.

Tirzepatide also got FDA approval for weight loss as an anti-obesity drug (on 8th November 2023)

It can be used alone or in combination with metformin or other drugs for treating the symptoms of type 2 diabetes.

What is Rybelsus?

Rybelsus (Semaglutide) is also a medication used to treat the symptoms of type 2 diabetes mellitus. It belongs to GLP-1 receptor agonists. It is an oral medication that is safe to use in adults over 18 years.

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Mounjaro vs Rybelsus – Mechanism of Action (MOA)



GLP-1 receptors are present all over the body including the beta cells.

These help control blood glucose, regulate blood glucagon levels, and enhance insulin secretion.

They are responsible for maintaining the proper balance of hormones that maintain the blood glucose concentration.

Similarly, GIP also promotes the secretion of insulin.

Mounjaro (Tirzepatide) works by agonizing both GLP-1 and GIP receptors, improving their concentration, and hence it aids in glycemic control and weight loss.

Rybelsus is a GLP-1 Receptor agonist. GLP-1 promotes insulin secretion, slows gastric emptying, and improves beta cell function.

Semaglutide is almost 94% similar to GLP-1 which is why it directly binds to GLP-1 receptors and causes beneficial effects on insulin sensitivity and glycemic control.


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Mounjaro vs Rybelsus – Pharmacokinetics




Half-LifeIt has a half-life of 5 daysIt has a half-life of 168 hours
BioavailabilityThe mean bioavailability of Mounjaro through subcutaneous injection is 80%The absolute bioavailability of Rybelsus is 89%


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Mounjaro vs Rybelsus for Weight Loss and Diabetes:

Mounjaro is considered one of the most highly potent diabetes medications as per the ADA 2023 recommendations.

In addition, it has been associated with the greatest weight loss observed with any medicines until now.

The table below shows the clinical efficacy of Tirzepatide in the SURPASS-1 Trial in obese diabetic patients:

SURPASS-1 Trial: Tirzepatide Vs Placebo

 Mounjaro 5 mgMounjaro 10 mgMounjaro 15 mg
Weight-7 kg-7.8 kg-9.5 kg

In a recent trial, the efficacy of Tirzepatide and Semaglutide in patients with type 2 diabetes was compared, and the results suggest that Tirzepatide at all doses (5,10, and 15mg) was superior to Semaglutide. [Ref]

The table below shows the comparison of Mounjaro (Tirzepatide) in different doses with once-weekly Semaglutide in a dose of 1 mg:

SURPASS-2 Trial: Tirzepatide Vs Ozempic 1 mg (Semaglutide)

 Mounjaro 5 mgMounjaro 10 mgMounjaro 15 mgSemaglutide 1 mg
Weight-7.6 kg-9.3 kg-11.2 kg-5.7 kg

It is evident in the above table that Semaglutide 1 mg is less potent than Mounjaro at any dose.

Similarly, another study reported that Tirzepatide at all doses was associated with a low rate of diabetes-related complications and improved life expectancy as compared to Semaglutide.

Moreover, the study results also showed that Tirzepatide is cost-effective against Semaglutide. [Ref]

One study compared Tirzepatide 5,10 and 15 mg with Semaglutide 2 mg. It was concluded that Tirzepatide 10 and 15 mg had significant effects when compared to Semaglutide 2 mg.

Furthermore, the lowest dose of Tirzepatide (5mg) was found to have similar reductions in body weight and HbA1c levels as the highest dose of Semaglutide. [Ref]

Tirzepatide is one of the potent weight loss medicines although it is not approved for weight loss. The SURMOUNT study demonstrates the weight loss results of Tirzepatide:

SURMOUNT-1 Trial: Tirzepatide Vs Placebo for weight loss

 Mounjaro 5 mgMounjaro 10 mgMounjaro 15 mg
Weight-15 kg-19.5 kg-20.9 kg
Waist Circumference-14 cm-17.7 cm-18.5 cm

As far as, the glycemic efficacy of Tirzepatide vs Semaglutide is considered, Tirzepatide was linked to improved beta cell function, insulin sensitivity, and glucagon secretions. Moreover, Tirzepatide and Semaglutide are also said to have similar safety profiles. [Ref]

Although not compared in head-to-head comparison trials, the A1C lowering effects and the weight loss effects of Mounjaro Vs Rybelsus are summarized in the table below:

Tirzepatide Vs Rybelsus: Comparing A1C and  weight loss effect

 Mounjaro (Tirzepatide)Rybelsus (Oral Semaglutide) [Ref]
 5 mg10 mg15 mg3 mg7 mg14 mg
Weight-15 kg-19.5 kg-20.9 kg-0.2 kg-2.3 kg-3.7 kg

The table above shows clearly that Mounjaro is superior to Rybelsus in terms of weight loss and A1C reduction as evidenced by clinical trials.

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Mounjaro vs Rybelsus – Side Effects



More Common

  • Difficulty breathing
  • Swallowing problems
  • Irregular heartbeat
  • Bloating
  • Fever
  • Skin rash or redness
  • Heartburn
  • Swelling of face or throat
  • Yellow eyes and skin
  • Constipation
  • Diarrhea
  • Acidity

Less Common

  • Bleeding
  • Blistering
  • Discoloration of skin
  • Ulceration at the injection site
  • Pain or numbness
  • Tingling


More Common

  • Blurred vision
  • Bloating
  • Chills and cold sweats
  • Confusion
  • Anxiety
  • Pale skin
  • Increased appetite
  • Indigestion
  • Dizziness
  • Irregular heartbeat
  • Dark-colored urine
  • Headache
  • Stomach pain
  • Nausea
  • Skin rash
  • Fatigue
  • Slurred speech

Less Common

  • Heartburn or acidity
  • Belching
  • Stomach discomfort

Mounjaro vs Rybelsus – Dosage


  • Mounjaro is recommended to be injected subcutaneously once a week at a dose of 2.5 mg. This is the starting dose, which can be gradually increased to 5 mg after 4 weeks. If an additional increase is required to achieve the desired glycemic control, 2.5 mg is added after 4 weeks.
  • The maximum weekly dose is 15 mg.
  • If a dose is missed, patients must take the medication within four days. If more than four days have passed, the dose must be skipped and the next dose administered.
  • It can be taken with or without food.
  • The most commonly used injection sites are the abdomen, thigh, and upper arm.
  • Do not combine the medication with insulin. Both must be handled separately.


  • The starting dose for Rybelsus is 3mg once daily. This can be increased to 7mg once daily after 30 days.
  • The maximum daily dose of Rybelsus is 14mg.
  • If a dose is missed then skip it and continue on to the following dose.
  • It is advised to take this medication 30 minutes before meals with a glass of plain water.
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Mounjaro (Tirzepatide) and Rybelsus (Semaglutide) improve glycemic control and promote weight loss therefore, both are useful in the treatment of type 2 diabetes mellitus. Both medications have almost similar side effects.

In terms of clinical efficacy, Tirzepatide causes more significant decreases in blood glucose levels and body weight as compared to Semaglutide.

However, Rybelsus is an oral medication that is easy to use compared to Mounjaro because it has an increased risk of injection site infections.

What do you think?

Written by Dr. Ahmed

I am Dr. Ahmed (MBBS; FCPS Medicine), an Internist and a practicing physician. I am in the medical field for over fifteen years working in one of the busiest hospitals and writing medical posts for over 5 years.

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