Rybelsus (Oral Semaglutide) for Weight Loss: Things to Know

Since the 1940s there has been a search for a ‘magic pill’ for weight loss by academics and the public. However, weight reduction is not as simple as an oral medication treatment and thus weight loss injections offer hope to persons who have tried out other oral products.

However to many patients injections are not the most convenient and welcome method of administering specific medications.  Well, what if the same can be achieved through a simple oral tablet?  Well, this could be a reality sooner than you think.

In 2019, Rybelsus® (semaglutide) was the first of these medicines belonging to a new generation of pills for the treatment of type 2 diabetes. This was after the approval of its injectable version which goes by the name of Ozempic entered the market.  Subsequently, higher doses have been medically authorised in obesity and commercialised as Wegovy.

Fast forward to today and Rybelsus is doing exactly what Ozempic did previously and that is to pursue a path of double digit increase in sales. And so far, its results have proved beneficial for weight loss as well. This is a major step in the enhancement of the discovery of oral therapies for obesity treatment because the injections which many patients cannot endure might be replaced by this compound in the future. 

But is oral semaglutide as effective as injections, such as Wegovy? Below are five things that you need to know about Rybelsus.

1. Rybelsus is a branded oral tablet that belongs to the same drug classification as Ozempic and Wegovy 

Rybelsus, Ozempic, and Wegovy are alike too because they all include semaglutide within their list of ingredients.  Semaglutide belongs to a class of medicines known as GLP-1 agonists which is antidiabetic.

It is important to note that Rybelsus, Ozempic, and Wegovy are similar drugs; they work in the same manner in your body.  After you have eaten your food they go ahead and tell your pancreas to release insulin and reduce gluconeogenesis in your liver. They also interfere with how fast the food can pass through stomach and affect the regions of brain involved with hunger and satiation.

All the three medications above can also result in similar side effects such as nausea, vomiting, and diarrhea. But again it needs to be understood that these side effects rarely persists and fade as the body formulates to the medication. No matter what medicine you will be prescribed, the beginning dose is low and gradually building up to the ideal one. This helps your body become used to medicine which brings down the number of side-effects.

As all these drugs can be said to be falling within the same family, they possess some differences however. The first thing that we notice is how each is managed or administered. The two drugs presented by the Wegovy and Ozempic are presented in injection formulation whereas drug in Rybelsus formulation is oral and is used daily as a pill.  Both of them are also used for cardiovascular purpose in some patients with heart diseases but Rybelsus cannot be used for it.

2. Rybelsus can be taken for diabetes but as of now it is in the trials for weight loss 

Now both Ozempic and Rybelsus are approved for use for Type 2 diabetes in adults.  Since weight loss is also a side effect of Ozempic, higher doses were researched for this effect – leading to the creation of Wegovy for the weight loss.  Likewise, Rybelsus is also on the path as well.

There are capsules for Type 2 diabetes for taking in the dosage of 3 mg, 7 mg and 14 mg of Rybelsus.  The 25 and 50 mg doses are currently in a clinical trial (OASIS 1) to determine whether they are effective in the weight management in adults.  These are individuals with BMI of 30 or more or, 27 or more along with one or more conditions related to obesity including hypertension.

The outcomes of carried out clinical trials have been positive. Earlier, the manufacturer of Rybelsus said that he would seek FDA’s approval to promote the dose of oral semaglutide at 50 mg. But, whether this has indeed happened is not very clear now as yet.  If it is approved for the weight loss, it will probably have a different name than the one marketed under Rybelsus.

3. Weight loss with higher doses of Rybelsus is as effective as with Wegovy 

So, then, how does Rybelsus compare to Wegovy?  There is no direct data on weight loss differences between the two drugs although isolated research investigations should offer some insight into the matter.

The OASIS 1 trial compared weight change in obese adults treated with oral semaglutide 50mg to those of placebo for 68 weeks.  People who took semaglutide lost about 17% of their body weight when the study commenced. 

This percentage of the weight loss is very impressive thus making it a real shot at fighting the ever increasing vice of obesity.  This concurs with large trial of Wegovy where on average it was showed that almost 15 percent weight loss in the same period.

4. The higher doses of Rybelsus are also being studied for Type 2 diabetes, proving a better glycemic and weight reduction impact 

Preliminary results of the Pioneer Plus trial are also assessing higher doses of Rybelsus for patients with Type 2 diabetes. For the condition, Rybelsus could come in five different doses if approved. At the moment, it comes as a three-dose product.

As with weight loss studies, the 25 and 50 mg in Type II diabetes led to a trend of more weight loss than the 14 mg dose. Hence, the implication appears to be that somewhat greater doses would tend to produce a deeper effect not only on glycemic regulation but on weight as well. The amount of weight loss for the 50 mg dose was a little over two times the amount of weight loss that the 14 mg dose provided.

However, the higher doses of Rybelsus helped to achieve significantly lower average blood glucose level during the preceding 3 months, measured with glycated hemoglobin A1C. 

From the above observations, it was also anticipated that the manufacturer of the Rybelsus would be seeking FDA approval for the 25mg and 50mg doses used in Type 2 diabetes in the next year.  However it is really hard to say whether the application has been submitted or not.

5. Rybelsus is not the only oral GLP-1 agonist currently in development for obesity, but it might be the most advanced one

Except for Rybelsus, other oral GLP-1 agonists are being explored in other weight loss procedures.  But they don’t have research and development that their level should have.  New orally administered GLP-1s might have advantages in the aspect of weight regulation and convenience compared to injectables based on the patients’ case.  However, they also look somewhat quite promising as well. A few examples include:

• Orforglipron: Once daily single shot non-injectable, orally active GLP-1 agonist in phase 3 clinical program. The average weight loss from prior clinical trial data in people taking it is shown to be feasible within the first 36 weeks to get to about 15% loss of initial body weight. Orforglipron is also simply under study for type II diabetes too.
• Danuglipron: An oral antidiabetic drug under Phase II clinical trial for obesity and Type 2 diabetes. The only weight loss trial which included a small sample of patients reported promising results, with up to 12% weight loss over 32 weeks at the dose of twice a day. However this manufacturer will go on with the study of a formulation in a modified release tablet which is a once daily dose.

Currently, all approved drugs that can be referred to the GLP-1 agonists class to which semaglutide pertains are peptides — substantially large molecules constructed of amino acids. This accounts for why they are terminated with “tide.” Orforglipron and danuglipron are small chemical drugs originated from chemical products. This is why they end with “glipron” instead. They are used alike but from molecular perspective, there is a great difference.

The Bottom Line

Rybelsus is a tablet formulation of semaglutide that has been recommended for the managing of Type 2 diabetes. Other than the diabetes type 2 treatment, Rybelsus appears in higher doses in trial for use in weight loss, not currently authorized by the FDA. They’re also being investigated in Type 2 diabetes which would give more choices of dosage for people with the disease.

It also was found that the higher doses of Rybelsus lead to similar weight loss as in a higher-dose injectable semaglutide called Wegovy. Based on these findings there is great potential with oral semaglutide to revolutionise the treatment of obesity and to make it easier to access effective weight loss treatment.  They also improve on weight loss and A1C as well as in patients who have type 2 diabetes.

Before the FDA announcement, its manufacturer had intended to apply for the sanction to market Rybelsus at higher doses to treat obesity and Type 2 diabetes.