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Rybelsus vs Januvia and Janumet – Comparing Efficacies

Rybelsus vs Januvia

rybelsus vs januvia and janumet weight reduction

Rybelsus Vs Januvia and Janumet is a comparison of the efficacies of the two drugs in terms of their weight-losing effects and glycemic control. Both these drugs have different pharmacokinetic properties which are also listed here.

Rybelsus is the newer generation GLP-1 analog. It is the orally available form of Semaglutide that is used to treat patients with Diabetes Mellitus Type 2. The other two formulations of this newer generation Semaglutide are:

  • Ozempic:
    • Ozempic is the injectable form of Semaglutide that is administered once a week. It has been approved by the FDA for the treatment of patients with T2DM. It is available as a 2 mg/1.5 mL (1.34 mg/mL) injection that can be either used as:
      • to inject 0.25 mg or 0.5 mg of the drug
      • 1 mg of the drug per injection.
  • Wegovy:
    • Wegovy is a once-a-week injection of Semaglutide that has recently been approved by the FDA for the treatment of individuals who are either obese or overweight with or without T2DM.
    • It is to be administered as a subcutaneous injection once a week in a dose of 2.4 mg. In clinical trials, Wegovy was associated with a weight loss of about 16% from the baseline at the end of the trial.

Comparing Rybelsus vs Januvia and Janumet:

Mechanism of action of Rybelsus and Januvia:

  • Rybelsus MOA:
    • Rybelsus is oral Semaglutide. It is the newer generation Semaglutide that is 94% structurally identical to the endogenous Semaglutide.
    • It primarily acts as an incretin mimetic and causes the release of insulin in a glucose-dependent manner. It also suppresses the release of glucagon and inhibits gastric motility.
    • It has direct and indirect effects on appetite suppression and is therefore associated with marked weight loss.

Wegovy MOA (Mechanism of action of Semaglutide)

  • Januvia MOA:
    • Januvia is the brand name of Sitagliptin. It is a DPP IV inhibitor that primarily acts by increasing the levels of endogenous GLP-1 levels.
    • DPP IV or dipeptidyl peptidase-IV enzyme is responsible for degrading the endogenous GLP-1. Thus, in normal individuals, the usual half-life of the endogenous is very brief.
    • Januvia inhibits the DPP-IV enzyme that is responsible for degrading the endogenous GLP-1, thereby, increasing the half-life of the endogenous GLP-1 resulting in a greater and sustained release of insulin, suppressing glucagon, and inhibiting gastric motility.
    • Janumet is the combination of Sitagliptin and metformin. The combination pill incorporates the mechanism of metformin as well and thus, Jaunmet also increases insulin sensitivity in the target tissues. It also inhibits glycogenolysis and gluconeogenesis.

Pharmacology of Rybelsus and Januvia

  Rybelsus Januvia
Class GLP-1 analog DPP-IV inhibitor
Dosage strength 3 mg, 7 mg, and 14 mg oral tablets 50 mg and 100 mg oral tablets. Also, available in combination with metformin as Janumet
Bioavailability 89% 87%
Half-life elimination One week 8 – 14 hours
Steady State concentration 4 – 5 weeks 4 – 5 days
Peak plasma concentration One hour after administration 1 – 4 hours

Rybelsus vs Januvia Weight loss Comparison:

The Pioneer -IV trial evaluated and compared the weight loss effects of Rybelsus and Januvia. In patients who had a baseline weight of 200 pounds (90.7 kgs), Rybelsus in a dose of 7 mg and 14 mg significantly reduced weight compared to Januvia 100 mg [Ref].

A mean weight loss of 4.8 pounds (2.2 kgs) and 6.8 pounds (3.1 kgs) was observed with Rybelsus administered in a dose of 7 mg and 14 mg daily compared to 1.3 pounds (0.6 kgs) only with Januvia (Sitagliptin) 100 mg daily.

People who took Rybelsus in a dose of 7 mg daily had a 3.69 times greater weight loss compared to Januvia 100 mg daily. Those who took Rybelsus in a dose of 14 mg daily had a 5 times greater weight loss compared to Januvia 100 mg daily.

rybelsus vs januvia and janumet weight reduction
After 26 weeks, weight was significantly reduced in patients taking Rybelsus vs Januvia

Janumet has a weight-neutral effect while Rybelsus resulted in significant weight loss as seen below:

rybelsus plus metformin compared to Sitagliptin 100 mg plus metformin for weight loss in diabetics after 26 weeks
Rybelsus plus metformin compared to Sitagliptin 100 mg plus metformin for weight loss in diabetics after 26 weeks

Rybelsus for Weight Loss in Non Diabetic Patients

Rybelsus Vs Januvia and Janumet glucose-lowering effect:

The Pioneer-IV Trial compared Rybelsus and Januvia in a head-to-head comparison. Patients had a mean baseline glycated hemoglobin of 8.3% [Ref]. There were three groups of patients:

  • One group of patients receives Rybelsus in a dose of 7 mg daily
  • One group received Rybelsus in a dose of 14 mg daily, and
  • the third group received Januvia (Sitagliptin) in a dose of 100 mg orally daily.

At the end of 26 weeks study period, Rybelsus reduced the HbA1C by 1% and 1.3% when administered in doses of 7 mg and 14 mg compared to an HbA1C reduction of only 0.8% with Januvia (Sitagliptin).

rybelsus vs januvia and janumet
Rybelsus 14 mg daily reduced the glycated hemoglobin significantly compared to 100 mg Januvia (Sitagliptin).

In Summary:

Rybelsus is a promising new drug added to the list of anti-diabetic medications. Apart from its efficacy in better controlling diabetes, it also has a superior weight-losing effect in diabetic patients when compared with Januvia (Sitagliptin).

Rybelsus VS Jardiance ( Oral Semaglutide Vs Empagliflozin)

What do you think?

Written by Diabetes Doctor

I am an Internist practicing medicine for the last fifteen years. Over the years, I have learned that medicine is not about prescribing pills. True medical practice is helping people.
I do prescribe pills as well but the best results I get are when I motivate people to overcome their problems with little changes in their lifestyles.
Since most of my patients are obese, have diabetes, hypertension, high cholesterol levels, I am writing at dibesity.com when free.
Dibesity, I know the correct word is diabesity. Ignore this! Be with us.

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