Rybelsus vs. Metformin: Similarities and Differences
Medically reviewed by Femi Aremu, PharmD
Rybelsus is a glucagon-like peptide-1 (GLP-1) agonist available as a tablet. It is used to treat type 2 diabetes. Metformin is a biguanide drug available as a tablet and an oral liquid. It is also used to treat type 2 diabetes, and is approved to be used in younger people compared to Rybelsus, which is only approved for adults.
Both of these drugs lower blood sugar levels associated with type 2 diabetes, but they work in different ways to control levels, come with a different range of side effects, and may be available at a significant difference in cost depending on your insurance coverage.
This article compares Rybelsus and Metformin, including how they work, their side effects, and their cost.
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What Is Rybelsus?
Rybelsus is the brand name of a type 2 diabetes medication that's available as tablets that are taken by mouth. The active ingredient in Rybelsus is semaglutide. There is no generic equivalent of Rybelsus.
Rybelsus is indicated for blood sugar control in adults with type 2 diabetes and is used in addition to diet and exercise.
Semaglutide is a drug contained in other products, such as Ozempic, an injection used to control blood sugars, and Wegovy, an injection indicated for weight loss. All of these semaglutide products are dosed differently. Rybelsus may help you lose some weight, but it is not a weight-loss drug.
How Does Rybelsus Work for Type 2 Diabetes?
Semaglutide belongs to the drug class known as glucagon-like peptide-1 (GLP-1) agonists. It works by mimicking the hormone GLP-1, which your body produces naturally.
This hormone helps regulate blood sugar by:
Telling your pancreas to produce insulin after you eat
Preventing your liver from releasing more sugar
Slowing down the speed at which food leaves your stomach
What Is Metformin?
Metformin is a type 2 diabetes medication as well, available generically but also sold under many different brand names, such as Glucophage (now discontinued), Glumetza, and Fortamet. Formulations may be tablets or liquid, regular or extended release.
Metformin is indicated for blood sugar control in adults and children 10 years and older with type 2 diabetes, used in addition to diet and exercise. This is very similar to the indication for Rybelsus, but the Rybelsus is only indicated for adults.
How Does Metformin Work for Type 2 Diabetes?
Metformin is the active ingredient in the medication and is the only drug currently available that belongs to the biguanide drug class. Metformin works in several different ways to control blood sugar, including:
Decreases the amount of glucose that your liver produces
Decreases the amount of glucose that gets absorbed into your digestive tract
Helps the rest of your body take in and use glucose properly
Rybelsus vs. Metformin: Key Differences
Key differences between Rybelsus and metformin are:
Metformin is indicated for use in people as young as 10 years old, whereas Rybelsus is only indicated for adults.
Metformin is also available in more types of medicine, such as extended-release tablets and oral liquid.
As a generic, metformin is generally a very affordable medication, whereas brand-name Rybelsus may be more costly.
Gastrointestinal side effects are the most commonly reported side effects of both drugs, but metformin is associated with a higher incidence of diarrhea or other similar symptoms.
Which Works Better?
Both of these drugs effectively lower blood sugar levels and hemoglobin A1c (an indicator of blood sugar control for the past three months). In studies, they have shown similar results, lowering blood sugar by about 1% to 2%.
If this decrease is not enough, you may end up taking both of these drugs together or either one with another type of diabetes medication. Some studies have shown that metformin plus another diabetes medication, like a GLP-1 agonist (such as Rybelsus), is more effective at lowering A1c than metformin alone.
If you have coexisting health conditions such as heart disease or you need to lose weight, you and your healthcare provider may be able to decide which is better to start you on by looking at the additional benefits these medicines provide.
Metformin may have an additional cardiovascular benefit compared to Rybelsus, but if weight loss is a more important focus, Rybelsus may be the better choice.
Dosing: How to Take Rybelsus and Metformin
Metformin is available as an oral tablet (both regular and extended-release formulas) and an oral liquid. If you take extended-release tablets, you may take them once a day. You may take regular-release tablets or oral liquid up to twice a day.
You will likely start at a metformin dose of around 500 to 1,000 milligrams (mg) once daily, and your healthcare provider may slowly increase your dose as you tolerate it up to 2,500 mg per day. Other tips for taking metformin correctly include:
Take metformin with meals, as this may help reduce side effects.
You can divide larger doses, those over 2,000 mg per day, into three doses.
Extended-release tablets should not be crushed or chewed but should be swallowed whole.
Extended-release tablets are also reported to cause diarrhea less frequently than regular tablets.
Rybelsus is available only as an oral tablet, taken once daily. You will most likely start at a dose of 3 mg daily and may increase to 7 or 14 mg daily as needed for additional blood sugar control.
Take Rybelsus first thing in the morning, at least 30 minutes before you take other oral medications or have anything to eat or drink. Tips for taking Rybelsus correctly include:
Take it with no more than 4 ounces of plain water.
Do not crush, split, or chew tablets; swallow them whole.
If a dose is missed, skip the missed dose and take the next dose on the following day.
Can You Take Rybelsus and Metformin Together?
If your blood sugar is not well controlled enough with only one option or the other, you may be prescribed both Rybelsus and metformin. Since these medications work differently, they may be taken at the same time.
Some studies have shown that metformin plus another diabetes medication like a GLP-1 agonist (such as Rybelsus) is more effective at lowering A1c than metformin alone.
Side Effects
The most common side effects that Rybelsus may cause include:
Abdominal pain
Constipation
Diarrhea
Vomiting or nausea
Headache
The most common side effects caused by metformin include:
Diarrhea
Vomiting or nausea
Cobalamin (vitamin B12) deficiency
Flatulence or gas
Asthenia, or lack of strength and energy
Headache
Precautions
Some safety warnings that should be considered more carefully than the above-listed side effects for Rybelsus include:
Acute and chronic pancreatitis (inflammation of the pancreas, an organ that aids in digestion) has been reported in people taking Rybelsus. If this is suspected, it should be discontinued, and if pancreatitis is confirmed, do not start taking Rybelsus again.
Acute gallbladder disease, such as cholelithiasis (gallstones) and cholecystitis (inflammation of the gallbladder), has occurred with this medication. If you lose weight quickly or a lot of weight, this may increase the risk for these conditions.
Diabetic retinopathy complications have been reported in people with type 2 diabetes and high cardiovascular risks; if you have ever been diagnosed with diabetic retinopathy, you may be more likely to experience complications while taking this medication.
Acute kidney injury and worsening of chronic renal (kidney) failure have occurred in people taking GLP-1 agonists. Make sure your healthcare provider is aware if you have kidney disease.
Personal or family history of thyroid cancer, particularly medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2)
Special precautions to be aware of before you start taking metformin include:
Do not take this medication if you have had acute or chronic metabolic acidosis, including diabetic ketoacidosis.
Metformin may cause low levels of vitamin B12 (cobalamin), so levels should be taken before you start metformin and then be continuously monitored.
If you have kidney disease and a glomerular filtration rate (GFR) between 30 and 45, metformin should be used with caution. Your GFR should continue to be monitored. If it falls below 30, metformin most likely needs to be stopped. GFR is a measure of kidney function.
If you need to have imaging studies done that require iodinated contrast (which can include computed tomography [CT] scans, fluoroscopy, angiography, and venography), make sure to let your healthcare provider who is ordering the imaging know that you take metformin. Some people must temporarily stop taking it before the imaging study. This applies to those with a low GFR (between 30 and 60), a history of liver disease, alcohol use disorder, or heart failure.
Drug Interactions
These drugs can interact with diabetes medications that lower blood glucose, including each other. If your healthcare provider puts you on multiple drugs to treat diabetes, make sure you have a plan to monitor your glucose regularly and are familiar with signs of hypoglycemia (low blood sugar).
Rybelsus
Remember to take Rybelsus at least 30 minutes before you eat, drink, or take any other oral medications because these can affect its absorption. You want this to be consistent to avoid high and low blood glucose levels. Other interactions include:
Chloroquine and hydroxychloroquine: These drugs (antimalarials also used for autoimmune and inflammatory diseases) may increase the effects of diabetes medications, resulting in lower blood sugars. If you take both of these medicines, you may need a lower dose of Rybelsus.
Fluoroquinolones: This class of antibiotics, including Levaquin (levofloxacin) and Cipro (ciprofloxacin), may affect your blood glucose levels, so be sure to monitor extra carefully if you need to take one of these antibiotics.
Levothyroxine: Taking levothyroxine (used for underactive thyroid) with Rybelsus may decrease the effectiveness of Rybelsus in controlling blood sugar and increase your exposure to levothyroxine.
Metformin
The interactions above with chloroquine and fluoroquinolone medications apply to metformin as well.
Metformin comes with a risk of lactic acidosis (high lactic acid levels in the blood). This risk can be increased if you also take medications such as carbonic anhydrase inhibitors such as Diamox (acetazolamide), Tagamet (cimetidine), Ranexa (ranolazine), or Topamax (topiramate).
Another unique interaction is between metformin and contrast media, which may be injected when imaging is needed, such as computed tomography (CT) or positron-emission tomography (PET) scans. Make sure your healthcare provider is aware that you take metformin in this case, as you may need to temporarily stop taking it until your scan is complete.
Summary
Metformin is a first-choice treatment for type 2 diabetes and has been used for decades. It is available as a regular tablet, an extended-release tablet, and an oral liquid.
It effectively lowers blood glucose and A1c levels but may cause side effects that are difficult for some people to tolerate, such as nausea or diarrhea. It is sold under multiple generic and brand-name products and is an affordable medication.
Rybelsus, a GLP-1 agonist, is another popular choice for treating type 2 diabetes. It is available only as a brand-name oral tablet (unlike injectable medications) and may be more expensive for some people. However, it may cause fewer side effects than metformin and may be a good option for people trying to lose weight.
Most people start on metformin first but may end up taking both of these medications if blood sugar is not well enough controlled with metformin alone, as an add-on to diet and exercise.
Read the original article on Verywell Health.
