6 Rybelsus Interactions and How to Manage Them
Key takeaways:
Rybelsus (semaglutide) is an oral medication that treats Type 2 diabetes. It’s similar to Ozempic and Wegovy, two injectable medications that also contain semaglutide.
It’s recommended to take Rybelsus first thing in the morning on an empty stomach. This is because it can interact with food, beverages, and other medications. Wait at least 30 minutes after your dose before ingesting anything else.
Rybelsus interacts with medications that lower blood glucose (sugar), such as insulin, sulfonylureas, and meglitinides. It may also affect the absorption of levothyroxine (Synthroid, Levoxyl) and other oral medications.
The best way to manage Rybelsus interactions is to prevent them upfront. Your healthcare team can help you check for interactions by reviewing your current medication list.
Table of contents
Rybelsus is an oral medication used to treat Type 2 diabetes. It contains semaglutide, just like the injectable medications Ozempic and Wegovy. But unlike injectable semaglutide, your Rybelsus dose needs to be timed around meals and other medications due to interactions.
Some Rybelsus interactions can interfere with how well Rybelsus works. Others can increase the risk of side effects or change how you absorb other oral medications. Fortunately, you can navigate potential Rybelsus interactions with some careful planning. We cover six of these interactions and how to manage them below.
1. Food and beverages
Rybelsus should be taken on an empty stomach. This is because food and beverages can interfere with how much Rybelsus you absorb. So it’s best to take Rybelsus first thing in the morning and wait at least 30 minutes before eating or drinking.
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You can take Rybelsus with water, but not with coffee, juice, or any other beverage. Even the amount of water you drink with your dose matters. Limit this amount to no more than 4 oz (about one-half cup).
If your schedule makes it difficult to take Rybelsus in the morning, talk to your healthcare team. They can discuss your options, which may include taking Rybelsus at night in certain situations. Or, you may be able to switch to an injectable form of semaglutide (such as Ozempic), since you can inject your dose at any time of day.
Keep in mind that drinking alcohol while you’re taking Rybelsus can worsen its side effects, such as nausea and vomiting. What’s more, the combination can also increase your risk of hypoglycemia (low blood glucose). So it’s best to avoid or limit alcohol while you’re taking Rybelsus.
2. Insulin
Insulin is used to treat diabetes. Similar to Rybelsus, it lowers blood glucose (sugar). When insulin is combined with Rybelsus, there’s an increased risk of hypoglycemia. Hypoglycemia happens if your blood glucose is less than 70 mg/dL. Symptoms include sweating, shakiness, and a fast heartbeat.
When taken by itself, Rybelsus has a low hypoglycemia risk. But it’s common to take Rybelsus with other diabetes medications, such as insulin, which can raise this risk. Your prescriber will design your medication regimen to help keep your blood glucose in a target range that’s not too low and not too high.
You don’t need to completely avoid combining insulin and Rybelsus, but your prescriber will plan your doses cautiously. This may include lowering your insulin dose. They may ask you to check your blood glucose at home more often to be sure it’s not getting too low. Tell them if you’re having frequent hypoglycemia episodes, since this could mean your dose is too high.
3. Sulfonylureas
Sulfonylureas are oral Type 2 diabetes medications that stimulate your pancreas to release more insulin. Examples include glipizide (Glucotrol), glimepiride (Amaryl), and glyburide (Diabeta, Glynase). Similar to insulin, taking sulfonylureas with Rybelsus can raise your risk of hypoglycemia.
Your prescriber may lower your sulfonylurea dose when you start Rybelsus. This may be done as a precaution to help lower the risk of hypoglycemia. After that, they may adjust your dose after seeing how you respond to treatment. But you should tell them if you’re experiencing hypoglycemia episodes after starting Rybelsus.
4. Meglitinides
Meglitinides are a type of oral medication for Type 2 diabetes that work in a similar way to sulfonylureas. Examples include repaglinide and nateglinide (Starlix). Taking meglitinides with Rybelsus can also increase the risk of hypoglycemia.
Similar to sulfonylureas, your prescriber may lower your meglitinide dose as a precaution when you start Rybelsus. If you’re having hypoglycemia episodes with this combination, it’s possible that your dose is still too high. They can make additional adjustments as necessary.
5. Levothyroxine
Levothyroxine (Synthroid, Levoxyl) is an oral medication for hypothyroidism. Similar to Rybelsus, it’s best to take levothyroxine first thing in the morning on an empty stomach. You should also separate it from other medications by at least 4 hours. But what happens if you’re taking levothyroxine and Rybelsus?
If you take Rybelsus and levothyroxine together in the morning, this may increase how much levothyroxine you absorb. That’s because Rybelsus can slow down how quickly your stomach empties. To manage this interaction, your prescriber may have you take Rybelsus in the morning and take levothyroxine at night — at least 3 hours after your evening meal.
Your prescriber may monitor your thyroid levels more closely and make any necessary medication adjustments.
6. Other oral medications
Rybelsus may also affect how you absorb other oral medications. This may be more concerning with medications that have a narrow therapeutic index. Examples include warfarin (Jantoven) and digoxin (Lanoxin). With these medications, small changes in your blood levels can have a big impact on safety and effectiveness.
However, studies haven’t found that Rybelsus significantly affects warfarin, digoxin, and several other medications. Even so, your prescriber may want to monitor your blood work more closely during treatment. Tell them if you notice any new or worsening side effects, which may be a sign of an interaction.
When should you contact your prescriber about Rybelsus interactions?
Your prescriber can help to minimize potential interactions anytime you start a new medication, including Rybelsus. Make sure you provide a current medication list for them to review. If you have any questions about Rybelsus interactions while you’re taking it, check with your care team.
Hypoglycemia may be a sign of a Rybelsus interaction, particularly if you’re taking it with other medications that lower blood glucose levels. Your healthcare team should provide information on symptoms to watch for and how to safely bring your levels back up. Tell them if you’re experiencing frequent hypoglycemia episodes, since this could mean your dose needs to be lowered.
The bottom line
Rybelsus (semaglutide) is an oral medication that treats Type 2 diabetes. Rybelsus interactions include medications that lower blood glucose (sugar), such as insulin, sulfonylureas, and meglitinides.
Rybelsus can also affect the absorption of oral medications. You may be told to take certain medications, such as levothyroxine (Synthroid, Levoxyl), at a different time of day while you’re taking Rybelsus. Others may require additional monitoring.
Your healthcare team will help you navigate how to safely take Rybelsus and lower the risk of problems from interactions.
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References
Hauge, C., et al. (2021). Effect of oral semaglutide on the pharmacokinetics of thyroxine after dosing of levothyroxine and the influence of co-administered tablets on the pharmacokinetics of oral semaglutide in healthy subjects: An open-label, one-sequence crossover, single-center, multiple-dose, two-part trial. Expert Opinion on Drug Metabolism and Toxicology.
Morales, J., et al. (2020). Practical guidance for use of oral semaglutide in primary care: a narrative review. Postgraduate Medicine.
Novo Nordisk. (2024). Rybelsus [package insert].
U.S. Food and Drug Administration. (2017). FY2015 regulatory science research report: Narrow therapeutic index drugs.
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