Rybelsus vs Januvia and Janumet - Comparing Efficacies

Rybelsus Vs Januvia and Janumet is a comparison of the efficacies of the two drugs. How effective are Rybelsus and Januvia and Janumet in controlling diabetes and weight loss, is discussed along with other basic similarities and differences.

What is Rybelsus?

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.

It is associated with significant weight loss, although, it is not approved for treating obesity in non-diabetic individuals.

The other two formulations of this newer generation of 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, up to a maximum weekly single dose of 2 mg.
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.

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What are Januvia and Janumet?

Januvia is the brand name of Sitagliptin. It is also available in combination with metformin as Janumet (Sitagliptin + metformin).

Sitagliptin is one of the commonly used DPP-4 inhibitors. It is indicated for the treatment of type 2 diabetes mellitus.

It can be administered once or twice daily. Januvia is a weight-neutral, euglycemic drug.

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Comparing Rybelsus vs Januvia and Janumet:

Mechanism of action of Rybelsus and Januvia:

Rybelsus MOA:

Rybelsus is oral Semaglutide. It is the newer generation of 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.

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 a 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.

Rybelsus acts as incretins while Januvia blocks the enzyme that degrades the incretins. The final outcome of both Rybelsus and Januvia is essentially the same.

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Other Similarities and Differences between Rybelsus and Januvia are highlighted in the table below:

Pharmacology of Rybelsus Vs 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 the administration	1 – 4 hours

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Rybelsus vs Januvia Weight loss Comparison:

Rybelsus and Januvia are both drugs used to treat diabetes. They have not been approved for the treatment of obesity.

However, the injectable formulation of Rybelsus, Wegovy has been approved by the FDA for the treatment of obesity in individuals with or without diabetes.

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.

	Rybelsus 7 mg	Rybelsus 14 mg	Januvia 100 mg
Weight Loss	4.8 lbs (2.2 kgs)	6.8 lbs (3.1 kgs)	1.3 lbs (0.6 kgs)
Times weight loss Vs Januvia 100 mg	3.69 times greater weight loss	5 times greater weight loss	–

People who took Rybelsus in a dose of 7 mg daily had 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

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Rybelsus Vs Januvia and Janumet for Diabetes:

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 7 mg	Rybelsus 14 mg	Januvia 100 mg
A1C reduction	1%	1.3%	0.8%
Times Rybelsus more effective than Januvia	1.25 times greater A1C reduction	1.625 times greater A1C reduction	–

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

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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).