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Medication Spotlight: Rybelsus

Ozempic (semaglutide) has been a game changer in the field of type 2 diabetes, and now Novo Nordisk has created an oral version called Rybelsus. The technology which enabled the development of Rybelsus is an innovative breakthrough.

Semaglutide works by acting like endogenous glucagon-like peptide 1 (GLP-1) and binding to the GLP-1 receptor to better control insulin and glucagon action. As a peptide,it can easily be degraded in the gastrointestinal tract due to acidity and pepsin activity. Ozempic bypasses this effect via subcutaneous administration. For Rybelsus, the oral formulation contains 300 mg of salcaprozate sodium (SNAC) which is a small fatty acid that acts as an absorption enhancer. It is hypothesized to increase transport across gastric cells and increase pH (reducing acidity).


Dosing: initiate therapy with 3 mg once daily. After 30 days, may increase to 7 mg once daily. After another 30 days, may increase to 14 mg once daily. This titration schedule is for tolerance purposes due to gastrointestinal adverse effects such as nausea, diarrhea and vomiting. Note: do not take 2 tablets of 7 mg to make up 1 tablet of 14 mg.

Rybelsus can be used in mild to moderate renal insufficiency (above 30 mL/min).


Administration: There is a specific set of instructions for taking Rybelsus to ensure the medication is effective and absorbed (think similar to oral bisphosphonates). The tablet must be taken 30 minutes before the first meal of the day, with no more than 120 mL of water. Any larger volume of water may lead to decreased absorption. It should be taken before any other medications, food or drink (except water).


Adverse Effects: Related to gastrointestinal symptoms. It may increase heart rate and cause acute pancreatitis. It may cause weight loss by delaying gastric emptying.


Drug Interactions: Rybelsus can cause hypoglycemia when combined with secretagogues (sulfonylureas, meglitinides) and insulin.


Role in Therapy:

Rybelsus has been studied as add-on therapy to metformin. Compared to Januvia and Jardiance, Rybelsus has superior A1c reduction. Compared to Victoza, Rybelsus has comparable A1c reduction.

Nowadays, clinical trials are looking for cardiovascular benefit rather than A1c lowering effect. Rybelsus does not have the cardiovascular benefit seen with other agents such as subcutaneous Ozempic or Victoza. A clinical trial called SOUL is underway to investigate cardiovascular benefit. Currently, we know that Rybelsus does not cause cardiovascular harm.

Rybelsus could be an alternative to Ozempic for patients who are not comfortable with needles. However, there is a risk of therapeutic failure if patients do not adhere to the specific administration instructions because at best, only 1% of the drug is absorbed. Rybelsus is an effective A1c lowering medication, but more information is needed regarding cardiovascular benefit.

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