Rybelsus vs Tradjenta (Oral Semaglutide Vs Linagliptin)

Rybelsus vs Tradjenta

Rybelsus vs Tradjenta is a review and comparison of two novel antidiabetic medications, Semaglutide, and Linagliptin.

Semaglutide is a GLP-1 (Glucagon-like peptide-1) analog while Linagliptin is a DPP-IV (dipeptidyl-peptidase-IV) inhibitor.

Linagliptin, like other DPP-IV inhibitors, acts by inhibiting the enzyme that is responsible for degrading the endogenous GLP-1. Thus, in essence, both drugs have the same effects and side effects.

Drug Class:

  • Rybelsus is an orally available Semaglutide. It belongs to the class of medications called GLP-1 analog. The drug has almost 94% structural similarity to the endogenous GLP-1.
  • Linagliptin is an orally available medicine of the class, DPP-IV inhibitors.
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Mechanism of action of Rybelsus vs Tradjenta (Oral Semaglutide Vs Linagliptin):

It is a GLP-1 analog. It reduces blood glucose by the following mechanisms:

    • It induces the secretion of insulin in a glucose-dependent mechanism. Insulin secretion is increased when blood glucose levels are elevated.
    • It inhibits the secretion of glucagon in a glucose-dependent mechanism. The inappropriate secretion of glucagon is inhibited as the plasma glucose levels are elevated.
    • It causes delayed gastric emptying resulting in the slow release of gastric contents into the intestine. This inhibits the rapid spike in blood glucose. It also causes early satiety and postprandial fullness.
  • Linagliptin (Tradjenta):

Linagliptin is a DPP-IV inhibitor (di-peptidyl-peptidase IV inhibitor). DPP IV are enzymes that inactivate the endogenous incretins (GLP-1 and GIP).

DPP-IV inhibitors including linagliptin inhibit the DPP-IV enzymes resulting in a prolonged half-life of incretins.

Incretins, in turn, cause the release of insulin from pancreatic Beta cells and inhibit the secretion of glucagon from the pancreatic alpha cells in a glucose-dependent manner. It also has other effects of incretins such as post-meal fullness and early satiety.

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Strengths and formulations available of Rybelsus Vs Tradjenta:

  • Linagliptin:

Linagliptin is available under the brand name Tradjenta. It is available as 5 mg tablets administered once daily.

Linagliptin is available in combination with:

    • metformin as Jentadueto
    • empagliflozin (Jardiance) as Glyxambi, and
    • as a triple combination with metformin and empagliflozin (Jardiance) as TriJardy XR.
  • Rybelsus:

Rybelsus is available as oral tablets. It is given in a dose of 3 mg once daily. The dose may be increased at monthly intervals to 7 mg and 14 mg if the target blood glucose or glycated hemoglobin is not achieved. The maximum daily dose should not exceed 14 mg.

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Duration and onset of action of Rybelsus vs Tradjenta (Oral Semaglutide Vs Linagliptin):

  • Rybelsus has a half-life elimination of about five days. It can stay in the body for about five weeks after the last administered dose.
  • Linagliptin has a half-life of about 12 hours. It is given as a once-daily dose.

How to administer Rybelsus and Linagliptin?

  • Both drugs can be administered after meals. To reduce gastrointestinal side effects, they can also be administered between a meal.

Safety in Pregnancy and lactation:

Both Rybelsus and linagliptin should be avoided during pregnancy and by breastfeeding mothers.

Semaglutide should be preferably stopped at least two months before a planned pregnancy.

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Safety in kidney and liver diseases:

Linagliptin is the only DPP-IV inhibitor that is considered to be safe in patients with renal impairment. It does not cause hypoglycemia and 80% of the drug is excreted via feces.

Dosage adjustment in patients with renal impairment is not required. The manufacturer has not recommended any dosage adjustments in patients with liver impairment either.

Rybelsus has not been studied in patients with renal or hepatic impairment.

However, it has been associated with acute kidney injury and should be avoided in patients with advanced renal or hepatic impairment or those with unstable liver or hepatic functions.

Rybelsus vs Tradjenta (Oral Semaglutide Vs Linagliptin) Price Comparison:

  • Each 5 mg Linagliptin tablet costs USD 18.49 per tablet.
  • Each tablet of Rybelsus 3 mg, 7 mg, and 14 mg costs USD 30.90.
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Blood Glucose lowering effects of Rybelsus vs Tradjenta (Oral Semaglutide Vs Linagliptin) – Comparing efficacies:

Although not directly compared, the blood-glucose-lowering effect of Rybelsus is superior to Linagliptin. In the Pioneer-2 Trial, patients in the Semaglutide group had a 1.3% reduction in HbA1C at the end of the trial.

In contrast to Semaglutide, linagliptin decreased the glycated hemoglobin by only 0.43% in a multi-centered trial [Ref].

Rybelsus has been directly compared in clinical trials with sitagliptin but not with Linagliptin.

In the Rybelsus compared to Sitagliptin, Rybelsus was found superior to Sitagliptin at doses of 7 mg and 14 mg daily but not at a dose of 3 mg daily [Ref].

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Rybelsus vs Tradjenta (Oral Semaglutide Vs Linagliptin) – Effect on body weight:

Semaglutide is a novel medicine. The injectable weekly formulation (Wegovy) has been approved as weight-loss medicine.

The oral tablet formulation, Rybelsus, has also been found in clinical trials to cause significant weight loss.

It has a similar weight-losing effect as Jardiance. It was found to cause a weight loss of 8.1 pounds at 26 weeks [Ref].

Linagliptin, on the other hand, is considered weight-neutral. In a randomized double-blind placebo-controlled trial, linagliptin did not cause significant weight loss compared to placebo after 24 weeks of treatment (0.4 kgs vs 0.5 kgs).

Sitagliptin, another DPP-IV inhibitor was directly compared with oral Semaglutide (Oral Rybelsus) in the Pioneer-3 trial.

Oral Rybelsus at a dose of 7 mg and 14 mg was found superior to sitagliptin for its weight-losing effects (1.6 kgs weight loss with 7 mg Rybelsus compared to 1.1 kgs with 100 mg sitagliptin and 2.5 kgs weight loss with 14 mg Rybelsus compared to 2.0 kgs with 100 mg sitagliptin) [Ref].

Rybelsus Dose


Januvia 100 mg

7 mg daily⇓ 1.6 kgs⇓ 1.1 kgs
14 mg daily⇓ 2.5 kgs⇓ 2.0 kgs

Weight loss comparison of Rybelsus in a dose of 7 mg and 14 mg compared to 100 mg Sitagliptin.

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Cardiac Safety of Rybelsus vs Tradjenta (Oral Semaglutide Vs Linagliptin):

Both Semaglutide and Linagliptin have been found non-inferior to placebo in terms of cardiac safety.

Rybelsus and Linagliptin have not been compared directly, however, one meta-analysis compared Semaglutide to other comparator antidiabetic drugs. It was concluded that both drugs have similar cardiac effects [Ref].

In Conclusion:

Rybelsus is superior to linagliptin in terms of efficacy (glycemic control).

It also causes greater weight loss compared to Tradjenta, however, both have similar cardiac safety profiles. Linagliptin is a better option in patients with renal impairment.

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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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