Rybelsus VS Jardiance ( Oral Semaglutide Vs Empagliflozin)

Rybelsus VS Jardiance

Rybelsus VS Jardiance – Which drug is more potent in reducing blood sugars? Which drug is better for weight loss? Which drug has a better safety profile? These are a few of the questions that’ll be answered here.

It is important to understand that the treatment of diabetes is individualized nowadays and no drug is considered a “Gold Standard” for the treatment of diabetes. Hence, understanding the comparisons between anti-diabetic drugs is essential.

Drug Class of Rybelsus Vs Jardiance:

Rybelsus or Oral Semaglutide is a long-acting GLP-1 analog (glucagon-like peptide analog) that activates the incretin receptors.

Jardiance or empagliflozin is an SGLT2 receptor inhibitor (sodium-glucose co-transporter 2) that inhibits the glucose filtered into the renal tubules back to the systemic circulation.

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Combinations and formulations of Rybelsus Vs Jardiance:

  • Oral Semaglutide is available as Rybelsus Tablets and Injectable Semaglutide is available as Ozempic and Wegovy injections.
  • Empagliflozin is available as Jardiance Tablets.

Empagliflozin is also available in combination:

  • with metformin as Synjardy, Synjardy XR, and Glyxambi.
  • as a triple combination of TRI-Jardy XR that contains empagliflozin, linagliptin, and extended-release metformin.

Mechanism of action of Rybelsus Vs Jardiance:

Rybelsus (Semaglutide):

  • Semaglutide is a GLP-1 analog that activates the endogenous incretin receptors. It reduces blood glucose by three major mechanisms:
    • It causes the secretion of insulin in response to high blood glucose (in a glucose-dependent mechanism)
    • It inhibits the inappropriate release of glucagon
    • It causes a delay in gastric emptying resulting in early satiety.
    • It also indirectly suppresses the appetite by acting on the satiety center in the hypothalamus.

Empagliflozin (Jardiance):

  • Jardiance or empagliflozin is an SGLT-2 inhibitor that acts on the Sodium-glucose transporter 2 receptors present in the proximal renal tubules.
  • It causes the inhibition of filtered glucose in the urine from getting reabsorbed into the systemic circulation.
  • Thus, it has a greater glucose-lowering effect when the plasma glucose is high and more glucose is filtered.
  • Contrary to that, when plasma glucose is low, less of it will be filtered into the kidney tubules. Thus, it also has a glucose-dependent mechanism and does not lower glucose in individuals with normal or low blood glucose.
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Jardiance Vs Rybelsus Dosing and administration:

Rybelsus is the oral formulation of Semaglutide that is administered orally daily. It is given in a dose of 3 mg once daily.

The dose is increased to 7 mg and then 14 mg after an interval of 30 days if required (as in patients who do not achieve their glycemic targets). The maximum dose is 14 mg orally once daily.

Injectable Semaglutide (Ozempic) injection is administered subcutaneously in a dose of 0.25 mg once a week.

The dose may be increased to 0.5 mg and 1 mg after four weeks in patients who do not achieve their target blood glucose.

Injectable Semaglutide has also been approved by the FDA for the treatment of Obesity. It is marketed by the brand name of Wegovy and administered as a 2.4 mg injection subcutaneously once a week.

Jardiance or empagliflozin is given orally at a dose of 10 mg once daily. The dose can be increased to the maximum daily recommended dose of 25 mg once daily.

Half-life elimination of Rybelsus Vs Jardiance:

Semaglutide has a half-life elimination of about one week. The drug stays in the systemic circulation for about five weeks after the last dose is administered.

Jardiance has a half-life elimination of about 12 hours (12.4 hours to be precise).

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Jardiance Vs Rybelsus: Safety in Pregnancy and lactation:

It is better to avoid both drugs during pregnancy. Semaglutide should be stopped at least two months before a planned pregnancy. Empagliflozin should be specifically avoided during the second and third trimesters.

These drugs have not been studied in lactating mothers. Jardiance may cause fluid depletion and affect milk secretion. Preferably, both drugs should not be used during pregnancy.

Safety in kidney and liver diseases:

In patients with liver disease, no dosage adjustments have been mentioned for both drug.

In patients with kidney impairment, Jardiance is contraindicated if the CrCl falls below 30 ml/minute. It can be given with caution if the CrCl is between 30 and 45 ml/minute.

Rybelsus and Ozempic have been associated with the development of acute kidney injury. Individuals with unstable kidney functions should avoid using Semaglutide.

Cost Comparison Of Rybelsus Vs Jardiance:

Rybelsus and Ozempic Cost:

  • Each tablet of Rybelsus (3 mg, 7 mg, and 14 mg) costs USD 30.90.
  • Each 2 mg/1.5 ml pen injector of Ozempic (0.25 mg and 0.5 mg) costs USD: 617.95
  • Each 2 mg/1.5 ml pen injector of Ozempic (1 mg) costs USD: 308.97

Jardiance Cost:

  • Each tablet of Jardiance 10 mg and 25 mg costs USD: 19.19
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Blood Glucose lowering effects of Rybelsus Vs Jardiance (Oral Semaglutide Vs Empagliflozin):

The glucose-lowering effect of oral Semaglutide (Rybelsus 14 mg) was compared to 25 mg Jardiance in the Pioneer 2 Trial.

At week 26, Rybelsus in a dose of 14 mg was found to be superior to Jardiance given in a dose of 25 mg daily.

The mean HbA1C reduction was 1.3% in patients who received Rybelsus VS 0.9% in patients who received Jardiance [Ref].

rybelsus vs jardiance primary outcome
Mean Change in HbA1C after 26 weeks of treatment with Rybelsus vs Jardiance.

In the same study, more patients achieved target glycemic control at 26 weeks. Nearly 70% of the patients in the Rybelsus group achieved the target HbA1C of 7% or more.

rybelsus vs jardiance secondary outcome
Pioneer 2 Trial: More patients in the Rybelsus group achieved the target HbA1C compared to Jardiance at week 26 of the study.
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Weight Lowering effects of Rybelsus Vs Jardiance (Oral Semaglutide Vs Empagliflozin):

Both drugs, Rybelsus, and empagliflozin cause a reduction in weight loss. The mechanism of action is different and the combination of the two agents might be superior to monotherapy alone.

Rybelsus is the oral formulation of Semaglutide and it is not approved for weight loss. Ozempic and Wegovy, however, are associated with significant weight loss.

Rybelsus 14 mg and Jardiance 25 mg were found in the Pioneer 2 Trial to have comparable weight-losing properties.

After 26 weeks, 8.4 and 8.1 pounds of weight loss were observed in patients in the Rybelsus and Jardiance groups respectively.

rybelsus vs jardiance effect on weight loss
After 26 weeks, Rybelsus and Jardiance resulted in a comparable weight loss in the Pioneer 2 Trial

Rybelsus and Jardiance has a comparable weight loss effect compared to placebo when both the drugs are administered in their maximum doses.


rybelsus plus metformin compared to jardiance 25 mg for weight loss in diabetics after 26 weeks
Rybelsus vs Jardiance: Comparing their effects on body weight
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Safety of Rybelsus Vs Jardiance (Oral Semaglutide Vs Empagliflozin):

Common Side effects of Rybelsus include:

  • Nausea,
  • Vomiting,
  • Fullness and early satiety,
  • Post-meals bloating,
  • Raised pancreatic enzymes, and
  • increased heart rate.

In addition, it is contraindicated in patients with medullary thyroid cancers, multiple endocrine neoplasia, and pregnancy.

It may also worsen diabetic retinopathy and diabetic gastroparesis. It can cause pancreatitis in a dose-dependent manner.

Side effects of Jardiance:

The most common adverse effect of Jardiance is urinary and genital infections. It can also cause euglycemic ketoacidosis and should be avoided in patients at risk of developing diabetic ketoacidosis. It can also cause dehydration and volume depletion resulting in renal failure.

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In Conclusion:

Rybelsus is a more potent antidiabetic medicine, however, it is more costly. Rybelsus is also more potent in inducing weight loss.

On the other hand, Jardiance is best for patients with heart failure.

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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