Rybelsus vs. Metformin for Type 2 Diabetes
Key takeaways:
Metformin is a first-choice medication that’s been used for decades to treat Type 2 diabetes. It’s available as an oral tablet, extended-release tablet, and liquid.
Rybelsus (semaglutide) is a newer, brand-name medication for treating Type 2 diabetes. It’s sometimes added to other medications, like metformin.
Rybelsus and metformin are both available as brand-name medications. But you can also find metformin as a lower-cost generic. GoodRx can help make your prescription more affordable.
Table of contents
If you have Type 2 diabetes, there are many treatments available to help manage your blood sugar. For many people, metformin is a first-choice option. And the way it works is so unique, that it’s being studied for potential benefits within and beyond diabetes.
But, you may have also heard about a newer medication called Rybelsus (semaglutide). It’s the first and only oral medication of its kind. Other medications that work the same way are only available as injections.
So, if Rybelsus and metformin are both taken by mouth — how are they different? And when would you pick one over the other? In this article, we’ll compare Rybelsus and metformin. Keep reading to learn the key differences in how they work and when they’re used.
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What is Rybelsus?
Rybelsus is a glucagon-like peptide-1 (GLP-1) agonist that was first approved in 2019. It’s only available as a brand-name medication. You can find it as an oral tablet in three different strengths: 3 mg, 7 mg, and 14 mg.
What conditions is Rybelsus approved to treat?
Rybelsus is FDA-approved for managing blood sugar levels in adults with Type 2 diabetes. It should be used in combination with a healthy diet and exercise.
How does Rybelsus work for Type 2 diabetes?
Rybelsus works by mimicking the actions of GLP-1, a gut hormone your body makes naturally. These actions help manage blood sugar levels a few different ways, including:
Stimulating your pancreas to release insulin after eating
Stopping your liver from releasing more sugar
Slowing down the speed at which food leaves your stomach
What is metformin?
Metformin has been used to treat Type 2 diabetes for decades. It was first approved in the U.S. in 1995. Generic metformin tablets are available in three different strengths: 500 mg, 850 mg, and 1,000 mg. It’s also available in other strengths and dosage forms, including Fortamet and Glumetza (extended-release tablets) and Riomet (oral solution).
What conditions is metformin approved to treat?
Metformin is FDA-approved for managing blood sugar in adults and children ages 10 years and older with Type 2 diabetes. The extended-release (ER) versions are only approved for adults.
How does metformin work for Type 2 diabetes?
Metformin works to manage blood sugar by:
Lowering how much sugar your body absorbs
Slowing or stopping your liver from making more sugar
Helping your body’s natural insulin work better to lower blood sugar
How are Rybelsus and metformin dosed and given?
Rybelsus and metformin both come as tablets that you take by mouth. But there can be some differences with how often and when you take them.
Rybelsus is taken once daily. It’s important that you take your dose first thing in the morning with 4 oz of plain water. And you should take it at least 30 minutes before you eat, drink, or take other medications.
Metformin can be taken with a meal at any time of day. But how often you take a dose depends on the form of metformin you use. If you’re prescribed immediate-release (IR) metformin, you’ll likely take a dose once or twice a day, depending on your healthcare provider’s instructions. If you’re taking ER metformin, you’ll likely take one dose daily with an evening meal.
How effective are Rybelsus and metformin for treating Type 2 diabetes?
Both Rybelsus and metformin are effective for treating Type 2 diabetes. Each has been shown to lower hemoglobin A1C — a 3-month average of blood sugar levels — by a little over 1%. But there are a few differences for when they’re used.
As mentioned earlier, metformin is considered a first-choice treatment for most people. And a recent review suggests it may have some additional cardiovascular benefits, too. But not everyone is able to take or tolerate metformin. In that case, other options may be used.
Rybelsus isn’t typically recommended as a first-choice treatment option. But it may be added to other medications — like metformin — for additional blood sugar-lowering effects. If you need to add a GLP-1 agonist to your regimen, Rybelsus is the only oral option.
However, Ozempic — the injectable version of Rybelsus — may be preferred if you also have heart disease. That’s because it can lower the risk of heart attack and stroke. This benefit hasn’t been confirmed with Rybelsus yet. In this case, Ozempic may be used alone or in combination with other medications.
Whether you’re prescribed Rybelsus, metformin, or different diabetes medications depends on several factors. You and your healthcare provider will decide on the best diabetes treatment plan for you.
What are the known side effects of Rybelsus and metformin?
Both Rybelsus and metformin commonly cause stomach-related side effects. These include nausea and vomiting, diarrhea, and abdominal pain. The good news is that they tend to go away over time. See how these side effects compare below:
| Side effect | Rybelsus | Metformin | Metformin ER |
|---|---|---|---|
| Diarrhea | 9%-10% | 53% | 10% |
| Nausea/vomiting | Nausea: 11%-20% Vomiting: 6%-8% |
Combined: 26% | Combined: 7% |
| Abdominal pain or discomfort | 10%-11% | 6% | Less than or equal to 5% |
Other common side effects of Rybelsus include lowered appetite and constipation. For metformin, these include upset stomach, weakness, and gas.
What are the serious side effects of Rybelsus and metformin?
Although rare, Rybelsus and metformin can also cause serious side effects. Both medications have boxed warnings — the FDA’s strictest warning for a medication.
Rybelsus has a boxed warning about thyroid C-cell tumors. This is due to findings from animal studies, but the risk for people isn’t known. Because of this, you shouldn’t take it if you have a personal or family history of medullary thyroid cancer.
Other serious side effects of Rybelsus include pancreatitis (inflamed pancreas), issues with diabetic eye problems, and acute kidney injury.
Metformin has a boxed warning for a potentially life-threatening condition called lactic acidosis. This is when lactic acid builds up in your blood. Certain people are at higher risk of lactic acidosis from metformin, including adults over age 65 and people with liver disease.
Both Rybelsus and metformin can rarely cause serious allergic reactions, including anaphylaxis. Call 911 or get emergency medical help if you’re having difficulty breathing or have swelling in your face, throat, or neck.
What interactions do Rybelsus and metformin have?
Rybelsus and metformin can interact with other medications. For example, both can potentially cause your blood sugar to drop too low. The chance of this happening goes up if they’re taken with insulin or other insulin-releasing medications, like sulfonylureas.
Examples of other medications that can interact with metformin include:
Diuretics (water pills), such as hydrochlorothiazide (Microzide)
Corticosteroids, such as prednisone (Rayos)
Phenytoin (Dilantin)
Topiramate (Topamax)
Rybelsus can affect how well your body absorbs other oral medications. To avoid this interaction, it’s important that you take Rybelsus exactly as instructed. This includes taking Rybelsus at least 30 minutes before you take other medications.
Make sure your healthcare provider and pharmacist have a current medication list to check for other possible interactions.
Can you take Rybelsus and metformin together?
Yes, you can take Rybelsus and metformin together. And they work in different ways to help manage your blood sugar.
As mentioned above, many people start with metformin. Other medications, like Rybelsus, may be added if more blood sugar-lowering effects are needed. You and your healthcare provider can discuss if additional medications are needed to help you reach your goals.
How to save on Rybelsus and metformin
Rybelsus and metformin are available as brand-name medications. But you can also find metformin as a lower-cost generic. GoodRx can help you navigate the many ways to save on your prescription.
Save with GoodRx. GoodRx can help you save over 89% off the average retail price of the generic version of metformin. Generic metformin’s price at certain pharmacies is less than $6 with a free GoodRx discount.
Save with a copay savings card. If you have commercial insurance, you may be eligible to pay as little as $10 for Rybelsus using a savings card from the manufacturer.
Save with patient assistance programs. If you’re uninsured or underinsured, you may be eligible for Rybelsus’ patient assistance program, which offers the medication free of cost.
The bottom line
Metformin has been used to treat diabetes for a long time, while Rybelsus was recently approved in 2019. Both medications are effective for lowering blood sugar levels.
Metformin is often the first-choice medication for this use. Rybelsus usually isn’t a first-choice option, but it may be added to metformin or other medications.
Talk with your healthcare provider to learn more about whether Rybelsus, metformin, or both are possible treatments for you.
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References
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Collins, L., et al. (2021). Glucagon-like peptide-1 receptor agonists. StatPearls.
Foucher, C. D., et al. (2021). Lactic acidosis. StatPearls.
Han, Y., et al. (2019). Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: A systematic review and an updated meta-analysis. Cardiovascular Diabetology.
Laurus Labs Limited. (2021). Metformin [package insert].
Novo Nordisk. (2021). Rybelsus [package insert].
Smits, M. M., et al. (2016). Gastrointestinal actions of glucagon-like peptide-1-based therapies: Glycaemic control beyond the pancreas. Diabetes, Obesity, & Metabolism.
U.S. Food and Drug Administration. (2019). FDA approves first oral GLP-1 treatment for type 2 diabetes.
