Rybelsus vs Metformin: Differences, Side Effects, and More

By Craig Sorkin, DNP, APN
Medically reviewed checkmarkMedically reviewed
October 4, 2022

Semaglutide (Rybelsus) and metformin are two oral diabetes medications prescribed for treating type 2 diabetes. Even though they treat the same condition, they work differently. In this article, we’ll discuss what the medications are, how they compare, side effects, and how each one works to address symptoms of diabetes.

What Is Rybelsus?

Semaglutide, available as the brand name Rybelsus, is a newer type of medication for the treatment of type 2 diabetes. It is not available as a generic. Rybelsus is used on its own or with other medications like metformin to manage type 2 diabetes.

Rybelsus is a glucagon-like peptide-1 (GLP-1) agonist. This type of drug is otherwise only available as an injection. Rybelsus is the only oral medication in this class of drugs. Rybelsus was first approved by the U.S. Food and Drug Administration (FDA) in 2019. It is available as an oral tablet in three-, seven-, and 14-milligram (mg) strengths.

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How does Rybelsus work?

Rybelsus is used to treat type 2 diabetes in combination with a healthy lifestyle, including diet and exercise. It helps lower blood sugar levels by acting like a hormone that the body makes in the gut called GLP-1. As a result, Rybelsus can stimulate the pancreas to release insulin after meals. Insulin takes glucose out of the blood and into the cells, lowering blood sugar levels and allowing glucose to be used as energy.

Rybelsus also stops the liver from releasing more sugar, which can help stabilize blood sugar levels. It can also slow down digestion, which can prevent higher spikes of blood glucose after meals.

What Is Metformin?

Metformin is a first-line medication for the treatment of type 2 diabetes. First approved in 1995, metformin is generally well-tolerated. It may be prescribed as an oral solution (Riomet), tablet, or extended-release tablet (Glumetza, others).

Metformin is FDA-approved for the treatment of type 2 diabetes in people ages 10 and older. Extended-release tablets are only approved for use in adults.

How does metformin work?

Metformin helps keep blood glucose levels stable in patients who have type 2 diabetes or other conditions that may impact glucose control. It reduces how much sugar is taken into the bloodstream and slows the liver from releasing more sugar. It also stimulates the body’s natural release of insulin.

Rybelsus vs Metformin: How Do They Compare?

While Rybelsus and metformin both treat type 2 diabetes and work to control blood sugar levels in the body, they have some differences.

Effective?Yes, not first-line treatmentYes, first-line treatment
Common side effectsDiarrhea, nausea, vomiting, abdominal discomfort, reduced appetite, constipationDiarrhea, nausea, upset stomach, vomiting, abdominal discomfort, gas, weakness
Serious side effectsRare but possible: thyroid tumorsRare but possible: lactic acidosis
Insurance coverageTypically, varying copaysYes, low or no copays
CostsCash price with no assistance can range from $700-$1,200.Cash price with no assistance averages $10.


Both Rybelsus and metformin work to treat type 2 diabetes, and both can effectively lower hemoglobin A1C. Hemoglobin A1C is a blood test that measures a three-month average of a person’s glucose levels. It is often used in addition to other glucose and insulin tests to determine whether diabetes is well managed.

Side effects

Both medications can cause some common side effects.

Possible side effects of Rybelsus include:

The most common side effects of metformin include:

  • Diarrhea
  • Nausea and upset stomach
  • Vomiting
  • Abdominal discomfort
  • Gas
  • Weakness

Though rare, serious side effects are possible for both medications. Possible serious side effects can include:

  • Rybelsus: FDA black box warning for thyroid C-cell tumors. People who have a family or personal history of medullary thyroid cancer should not take Rybelsus. Other serious risks: inflammation of the pancreas (pancreatitis), kidney damage, and eye problems relating to diabetes.
  • Metformin: FDA black box warning for lactic acidosis. Adults over age 65 and people who have liver disease are at higher risk from this complication, where lactic acid builds up to dangerous levels in the blood.

Warnings and risks

Both Rybelsus and metformin have a small chance of causing anaphylactic allergic reactions. Anyone who takes either medication and experiences the following symptoms should seek emergency medical care of call 911:

  • Breathing problems
  • Hives
  • Rashes
  • Chest pain
  • Sudden vomiting

Both Rybelsus and metformin can interact with other medications. If taken incorrectly, both could lead to hypoglycemia (low blood sugar), which if not monitored properly can be serious. Neither medication should be combined with other medications for treating type 2 diabetes without a healthcare provider’s instructions.

Always tell your healthcare provider and pharmacist about any medications, OTC drugs, herbal supplements, or vitamins that you take. All can potentially lead to preventable drug interactions.


The cost of Rybelsus and metformin can vary widely.

  • Rybelsus: Only available as a brand-name drug, a typical dosage and monthly supply of tablets can range from $700-$1,200 depending on location, pharmacy, and insurance coverage. Manufacturer patient assistance programs may lower the cost dramatically or provide Rybelsus at no cost to people who meet eligibility requirements.
  • Metformin: Available as a generic, a typical dosage and monthly supply of tablets can range from $2-$20 depending on the location, pharmacy, insurance coverage, and the use of prescription savings programs.

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Which Works Better for Type 2 Diabetes?

Both Rybelsus and metformin are effective for balancing blood sugar in people who have type 2 diabetes. The medication that works best depends on many factors, such as:

  • Individual health and family history
  • Tolerance of side effects
  • Lifestyle changes like diet and exercise
  • Other health conditions
  • Accessibility and cost of medication

A medical provider will recommend the pharmaceutical medication that they believe will work best for a patient’s unique set of healthcare needs. If a medication is not covered by insurance or is not accessible because of cost, healthcare providers will work to find an effective and affordable treatment plan.

Bottom Line

Metformin has been used for almost three decades to treat type 2 diabetes. Rybelsus has only been used for a few years, but both provide similar results for balancing hemoglobin A1C levels.

Metformin is a first-line choice for healthcare providers, although Rybelsus is sometimes used with metformin or may be prescribed for people who are unable to take metformin.

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Frequently Asked Questions

Does Rybelsus work better than metformin?
Rybelsus and metformin work equally well to lower blood sugar levels in patients who have type 2 diabetes.
Should I take Rybelsus and metformin?
Metformin and Rybelsus are sometimes prescribed together to manage type 2 diabetes. If your healthcare provider has prescribed both medications together, take them as instructed.
What medication is better than metformin?
Metformin is a first-line prescription medicine used to treat type 2 diabetes because it is effective, generally well-tolerated, and covered by most insurance plans. Insulin therapy can also be effective for diabetes management, however, insulin must be more closely managed and can be much more expensive.
What drugs are comparable to Rybelsus?
Rybelsus is the same drug as Ozempic, known as semaglutide. Both are approved by the FDA to treat type 2 diabetes and manage blood sugar levels. Rybelsus is available as an oral tablet, while Ozempic is a once-weekly injection.

K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

Craig Sorkin, DNP, APN

Craig Sorkin, DNP, APN is a board certified Family Nurse Practitioner with over 15 years experience. He received his Undergraduate and Graduate degrees from William Paterson University and his doctoral degree from Drexel University. He has spent his career working in the Emergency Room and Primary Care. The last 6 years of his career have been dedicated to the field of digital medicine. He has created departments geared towards this specialized practice as well as written blogs and a book about the topic.

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