Managing Type 2 diabetes effectively requires the right medication. Two popular drugs are Rybelsus and Metformin, both FDA-approved to help control blood sugar levels in adults with this condition. While they share the common goal of managing diabetes, they function differently in the body and come with their own sets of benefits and potential side effects. But which one is better for you?

In this article, you will learn about the key differences between Rybelsus and Metformin, including their mechanisms of action, dosage forms, side effects, and cost comparisons. We will also explore how these medications impact weight loss and whether they can be used together for better diabetes management.

Key Takeaways

  • Rybelsus belongs to the class of GLP-1 agonists and works by imitating the actions of the natural hormone GLP-1, while Metformin works by reducing the amount of sugar produced by the liver and making cells more sensitive to insulin.
  • Metformin is approved for use in both adults and children aged 10 years and older, whereas Rybelsus is approved for adults only.
  • While Metformin may cause taste disturbances and gastrointestinal issues, Rybelsus’s potential side effects include affecting the absorption of other medications, thyroid cancer risk, pancreatitis, and retinopathy.
  • Rybelsus is available as an oral tablet, while Metformin is available in various forms, including regular oral tablets, extended-release tablets, and oral liquid.
  • Metformin has a shorter half-life of 4.5 hours and is available in generic form, whereas Rybelsus has a longer half-life of 168 hours and is not available in generic form.
  • Rybelsus may impact weight loss, while Metformin is noted for its weight management effects in many patients.

Comparing Rybelsus vs Metformin

Generic NameMetforminSemaglutide
Brand NamesGlumetza, Glucophage, FortametRybelsus, Ozempic, Wegovy
Drug ClassBiguanideGLP-1 Agonist
PrescriptionYes, prescription onlyYes, prescription only
IndicationsTreatment of type 2 diabetesImproves blood sugar in adults with type 2 diabetes
Age approvalApproved for use in adults and children aged 10 years and olderAdults only
Common Side EffectsTaste disturbances, diarrhea, stomach issuesMay affect the absorption of other medications, thyroid cancer risk, pancreatitis, retinopathy
Dosage Forms AvailableOral solution, oral tablet, extended-release tabletOral tablet
Half-Life4.5 hours168 hours
Generic AvailableYesNo
Weight Loss PotentialMay assist with weight lossMinimal impact on weight
Average US Price$2,895.00

(500 Tablets)


(30 tablets)

Our Price$519.00$297

Rybelsus Semaglutide TabletsWhat is Rybelsus?

Rybelsus is an FDA-approved medication for Type 2 diabetes in adults and belongs to a class of drugs known as GLP-1 agonists. This type of medication works by imitating the actions of a natural hormone in your body called glucagon-like peptide-1 (GLP-1). Here’s how Rybelsus helps manage diabetes:

Taking Rybelsus stimulates your pancreas to produce more insulin right after you eat, which is crucial because it helps lower your blood sugar. Additionally, Rybelsus slows down the process by which your liver releases sugar into your bloodstream, helping prevent spikes in your blood sugar levels.

Rybelsus also slows down digestion, meaning the stomach empties food into the intestine more slowly. This helps moderate blood sugar increases after meals and reduce appetite, which can indirectly support weight management. Although Rybelsus has shown some effectiveness in helping weight loss, the FDA does not officially approve it. Its main use remains the management of Type 2 diabetes by stabilizing blood sugar levels.

What is Metformin?

Metformin is one of the longest-used medications for managing Type 2 diabetes, first approved in the United States in 1990. Over the years, it has become the go-to first choice for many doctors treating diabetes due to its effectiveness and safety profile. Metformin works by reducing the amount of sugar that your liver releases into your blood, it enhances the effect of insulin (the hormone that controls blood sugar levels) in your body by making your cells more sensitive to it.

It also decreases the amount of sugar absorbed by your stomach and intestines from your diet. This multi-faceted approach helps to prevent spikes in blood sugar levels throughout the day, which is crucial for managing diabetes. Metformin is approved for use in adults and children aged 10 years and older, making it a versatile option for managing Type 2 diabetes across different age groups.

While primarily used to control blood sugar, Metformin has also been noted for its weight management effects in many patients. However, it’s important to note that it is not FDA-approved for weight loss.

Metformin Box

How Are Rybelsus and Metformin Administered?

Rybelsus is an oral tablet that should be taken on an empty stomach first thing in the morning. It’s important to swallow the tablet whole with no more than 4 ounces of plain water.  After taking Rybelsus, it’s crucial to wait at least 30 minutes before eating, drinking, or taking other oral medications. The starting dose of Rybelsus is typically 3 mg daily, which can be increased to 7 mg and then to 14 mg based on the patient’s need for additional blood sugar control and their tolerance to the medication.

Metformin is available in various forms, including regular oral tablets, extended-release tablets, and oral liquid. Regular metformin tablets can be taken with meals to reduce digestive side effects. On the other hand, extended-release tablets should not be crushed or chewed but swallowed whole. This form of metformin is beneficial as it has fewer gastrointestinal side effects and can be taken less frequently.

Metformin dosing typically starts at 500 mg to 1,000 mg once daily, possibly increasing to a maximum of 2,500 mg per day depending on the patient’s response and tolerance. Extended-release tablets simplify the dosing schedule with once-daily administration.

Which Works Better for Type 2 Diabetes?

Rybelsus and Metformin are both effective medications for managing Type 2 diabetes. They work in different ways to help control blood sugar levels. Metformin, a well-established drug used for decades, is often the first-line treatment for Type 2 diabetes. Studies have shown that Metformin can lower A1C levels by about 1.5% on average and diabetes incidence by about 18-34% on average.

Rybelsus, a newer medication, and the first oral GLP-1 receptor agonist, has been shown in clinical trials to reduce A1C levels by about 1% to 1.5%. For example, in a study involving 703 participants, Rybelsus demonstrated a significant reduction in A1C, with many patients achieving an A1C under 7%, which is a common target for people with diabetes to reduce the risk of complications.

Both medications are effective for lowering A1C levels, but they may be chosen based on different patient needs and conditions. Metformin is typically recommended as the first medication for most people with Type 2 diabetes due to its proven effectiveness, safety profile, and cost. Rybelsus may be chosen for patients who need additional glycemic control despite using other medications or for those who prefer an oral treatment option over injectable GLP-1 receptor agonists.

Rybelsus vs Metformin for Weight Loss

Rybelsus and Metformin are both known for their potential to aid in weight loss. In a 6-month study, adults taking the higher 14 mg dose of Rybelsus lost about 8 pounds, while those on the 7 mg dose lost around 5 pounds. These results compare to a weight loss of approximately 3 pounds in those who took a placebo, all while maintaining a regular diet and exercise routine.

On the other hand, Metformin has shown effectiveness in promoting weight loss in overweight and obese individuals who are not diabetic. A study found that people at high risk for developing diabetes who took metformin lost an average of about 2.1 kilograms (around 4.6 pounds) over a few years. The weight loss was more significant in those who consistently took their medication compared to those who didn’t.

In another study involving 154 patients treated with up to 2,500 mg of metformin daily, the average weight loss over six months was about 5.8 kilograms (around 12.8 pounds), representing a 5.6% reduction from their initial weight. This contrasts with a control group of 45 untreated patients who, on average, gained about 0.8 kilograms.

Notably, patients with severe insulin resistance, a condition where the body’s cells do not respond effectively to insulin, experienced more significant weight loss compared to those with better insulin sensitivity. This suggests that metformin’s weight loss benefits might be more pronounced in individuals with higher levels of insulin resistance.

Can you Take Metformin and Rybelsus Together?

Yes, Rybelsus and Metformin can be used together to manage Type 2 diabetes. This combination is beneficial because each medication works in different ways to control blood sugar levels, which can lead to more effective disease management. Studies suggest that combining Metformin with a GLP-1 receptor agonist like Rybelsus may enhance A1C reduction more effectively than either drug alone. Using both medications together allows them to complement each other’s actions.

For instance, while Metformin reduces the liver’s sugar production, Rybelsus helps by further regulating insulin levels and delaying how quickly food leaves the stomach, thus providing a more comprehensive treatment strategy. This can be particularly useful for patients not achieving their target blood sugar levels with a single medication.

However, patients need to consider potential side effects from each medication and discuss them with their healthcare provider to ensure the combination suits their specific health needs.

Handful of medication

What Are the Common and Serious Side Effects of Rybelsus and Metformin?


The most common and severe side effects associated with Rybelsus may include:

Common Side Effects:

  • Abdominal pain: Many users report discomfort in the stomach area, ranging from mild to severe.
  • Constipation: A reduction in the frequency of bowel movements, often accompanied by difficulty passing stools.
  • Diarrhea: Frequent loose or watery bowel movements, which can lead to dehydration if severe.
  • Vomiting or nausea: These symptoms can occur, particularly when starting the medication or increasing the dose.
  • Headache: Some users experience headaches, which can vary in intensity.

Serious Side Effects:

  • Pancreatitis: Rybelsus has been associated with both acute and chronic pancreatitis. If pancreatitis is suspected, the drug should be discontinued immediately.
  • Gallbladder disease: Conditions like gallstones and cholecystitis have occurred, potentially linked to rapid weight loss induced by the medication.
  • Diabetic retinopathy complications: Those with a history of diabetic retinopathy may experience worsening of this condition while on Rybelsus.
  • Kidney issues: There have been reports of acute kidney injury and worsening of chronic kidney disease.
  • Thyroid cancer risk: Although rare, there is a warning for an increased risk of thyroid C-cell tumors, so it’s not recommended for use in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2).


The most common and severe side effects linked to metformin may include:

Common Side Effects

  • Diarrhea: This is one of the most common side effects, particularly when initiating treatment.
  • Vomiting or nausea: These symptoms can also occur, especially when taken on an empty stomach.
  • Vitamin B12 deficiency: Long-term use of Metformin can lower Vitamin B12 levels, which might necessitate supplementation.
  • Flatulence: An increase in gas production can occur, leading to discomfort.
  • Asthenia: Users may feel unusually tired or weak.
  • Malabsorption syndrome: There can be general issues with nutrient absorption, although this is less common.

Serious Side Effects

  • Lactic acidosis: A rare but serious condition characterized by an accumulation of lactic acid in the body, which can be life-threatening. This is more likely to occur in patients with kidney issues or conditions that predispose them to lactic acid build-up.
  • Hypoglycemia: When used in combination with other diabetes medications, there might be a risk of low blood sugar levels.
  • Severe kidney problems: If renal function declines, Metformin accumulation can lead to toxicity, so kidney function monitoring is essential.

Rybelsus vs Metformin Cost

StrengthQuantityUS PriceBCI PriceSAVINGS
Rybelsus3mg30 tablets$1,078$29772%
60 tablets$2,147$57073%
90 tablets$3,216.00$810.0075%
7mg30 tablets$1,078$305.0072%
60 tablets$2,147$580.0073%
90 tablets$3,216.00$855.0073%
14mg30 tablets$1,078$315.0071%
60 tablets$2,147$610.0072%
90 tablets$3,216.00$900.0072%
Metformin ( Glumetza)500mg500 tablets$2,895.00$519.0082%
1,000 tablets$5,785.00$990.0083%
1,500 tablets$8,674.00$1,470.0083%
Metformin (Glucophage)500mg100 tablets$68.54$59.0014%
200 tablets$130.08$110.0015%
300 tablets$185.12$150.0019%

Customers purchasing Rybelsus and Metformin from Buy Canadian Insulin can use coupon code FIRST10 to save 10% on their initial order of Rybelsus or Metformin.

Final Thoughts

Both Rybelsus and Metformin are effective medications for managing Type 2 diabetes, each working in different ways to help control blood sugar levels. Metformin, a well-established drug, is often the first-line treatment for Type 2 diabetes and has been shown to lower A1C levels by about 1.5% on average. On the other hand, Rybelsus, a newer medication, has been shown in clinical trials to reduce A1C levels by about 1% to 1.5%.

Ultimately, the choice between the two medications depends on various factors, including individual patient needs, tolerability, and potential side effects. It’s important to consult with a healthcare professional to determine the most suitable treatment option based on personal circumstances.

FAQs About Rybelsus and Metformin

Which is better, metformin or Rybelsus?

Whether metformin or Rybelsus is better depends on individual health conditions and treatment goals. Metformin is often the first-line treatment for type 2 diabetes due to its effectiveness, safety profile, and low cost. It helps lower blood glucose levels by improving insulin sensitivity. Rybelsus (semaglutide) is a newer medication and is taken orally as a GLP-1 receptor agonist. It not only helps control blood sugar but can also promote weight loss. The choice between the two should be made in consultation with a healthcare provider, considering factors like efficacy, side effects, and cost.

Can I take Rybelsus without metformin?

Yes, Rybelsus can be taken without metformin. It can be prescribed as a monotherapy for individuals who cannot tolerate metformin or have contraindications to it. Always consult a healthcare provider before making any changes to your medication regimen.

Is Rybelsus more expensive than metformin?

Yes, Rybelsus is generally more expensive than metformin. Metformin is available as a generic medication and is typically very affordable. Rybelsus, being a newer brand-name medication, costs significantly more. Insurance coverage and specific pharmacy prices may vary, so checking with a healthcare provider and pharmacist can provide more specific cost information.

What is a good substitute for Rybelsus?

Good substitutes for Rybelsus include other GLP-1 receptor agonists like Ozempic (semaglutide injection) or Victoza (liraglutide). Depending on individual treatment needs, other classes of diabetes medications, such as SGLT2 inhibitors (e.g., Jardiance) or DPP-4 inhibitors (e.g., Januvia), might also be considered.

What is the generic name for Rybelsus?

The generic name for Rybelsus is semaglutide.

What happens when you stop Rybelsus?

Stopping Rybelsus can lead to an increase in blood sugar levels as the medication’s glucose-lowering effects wear off. Patients should consult their healthcare provider before discontinuing the medication to discuss alternative treatments and avoid potential complications.

Is metformin alone enough for diabetes?

Metformin alone may be sufficient for many individuals, especially in the early stages of type 2 diabetes. However, as the disease progresses, additional medications may be needed to maintain optimal blood sugar control. A healthcare provider can determine the best treatment plan based on individual needs.

Can I stop taking metformin when my sugar is back to normal?

Stopping metformin or any diabetes medication should only be done under the guidance of a healthcare provider. If medication is discontinued, blood sugar levels can rise again, so it’s important to have a plan in place to maintain diabetes control.

What is a natural replacement for metformin?

There is no exact natural replacement for metformin, but some lifestyle changes can help manage blood sugar levels. These include a healthy diet, regular exercise, weight management, and possibly supplements like berberine or cinnamon. Always consult a healthcare provider before starting any supplement or making significant lifestyle changes.

Sources (2021). Highlights of prescribing information: RYBELSUS (semaglutide) tablets, for oral use. Retrieved from

Aroda, V. R., & Ratner, R. E. (2018). Metformin and Type 2 Diabetes Prevention. Diabetes Spectr, 31(4). Retrieved from

Patel, D., Ayesha, I. E., Monson, N. R., Klair, N., Patel, U., Saxena, A., & Hamid, P. (2023). The Effectiveness of Metformin in Diabetes Prevention: A Systematic Review and Meta-Analysis. Cureus, 15(9).

Novo Nordisk. (2023, April). RYBELSUS® Results. Retrieved from

Seifarth, C., Schehler, B., & Schneider, H. J. (2013). Effectiveness of metformin on weight loss in non-diabetic individuals with obesity. Experimental and Clinical Endocrinology & Diabetes, 121(1), 27-31.

National Library of Medicine. (2017, August). Glucagon-Like Peptide 1 Receptor Agonists for Type 2 Diabetes. PubMed Central.