Rybelsus vs Metformin Comparison for Diabetes Treatment

Rybelsus (oral semaglutide) and metformin are both medications used for the treatment of type 2 diabetes. Type 2 diabetes is a medical condition in which the cells in your body become resistant to insulin. Insulin is required by your cells to take up glucose from the blood and use it for energy. If blood sugar levels stay high for a prolonged time, it causes damage to other organs in the body and increases your risk of heart attack, stroke, kidney disease, vision problems and nerve problems. Thus, it is important to control your blood sugar levels within target range if you have diabetes. Metformin has been the mainstay of treatment for a long time and is often the first medication typically prescribed for type 2 days, whereas Rybelsus has only been approved and available for a short time. In this article, we will compare Rybelsus vs Metformin.

How does it work?

Rybelsus works by getting your body to produce more insulin when blood sugar level is high. It slows down the emptying of the stomach and also works in areas of the brain that regular appetite and caloric intake.

Metformin works by by increasing your body’s sensitivity to insulin and thereby promoting cells and muscles in your body to take up more glucose. It also reduces glucose production by the liver. This helps to control your blood sugar levels. Although it is mainly used for treatment of type 2 diabetes, it may also be used in patients with pre-diabetes to try to prevent progression to diabetes. 

Rybelsus vs Metformin: How well does it work for blood sugar control?

The A1C test, also known as hemoglobin A1C, measures your average blood sugar levels over the past 3 months and is used to measure your blood sugar control to ensure your diabetes is under control. A A1C greater than 6.5% confirms the diagnosis of diabetes. Typical A1C goal for diabetes is less than 7% for most people, some patients may have slightly higher or lower individualized goals.

Rybelsus has been shown to lower your A1c by 1.2% to 1.4% in clinical trials. [Ref]

Metformin is estimated to lower your A1C by 1% to 1.3 %. [Ref]

What is the usual dose?

Rybelsus is usually started at 3 mg once daily dose for 30 days and then increased to 7 mg once daily. After 30 days on the 7 mg dose, it can be further increased to 14 mg once daily dose if better blood sugar control is needed. It is started low and gradually increased to reduce the risk of experiencing side effects.

Rybelsus should be taken on an empty stomach, 30 mins or more before the first food, beverage of the day.

Metformin is usually starter at a lower dose and then gradually increased to reduce the risk of experiencing side effects.

Regular-release tablets: Typically taken once to three-times daily with meal with a usual max dose of 2.5 grams per day total

Extended-release tablets: Typically taken once a day with evening meal

Metformin is primarily removed from your body by your kidneys. If you have kidney disease and decreased kidney function, you may need to adjust the dose of metformin. Patients with advanced kidney disease should not be taking metformin.

What are the side effects?

The most common side effects of Rybelsus are nausea, stomach pain, diarrhea, decreased appetite and vomiting. It is started at a lower dose and increased gradually to reduce the risk of experiencing these side effects and they tend to decrease over time.

A rare side effects is inflammation of your pancreas (pancreatitis). If you have severe pain in your stomach/back area that will not go away with or without vomiting, you should stop taking Rybelsus and seek medical attention.

In studies with rodents, Rybelsus caused thyroid tumours including thyroid cancer; it is not known whether it can cause the same in humans. If you or someone in your family has medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), you should not take Rybelsus. Monitor for symptoms of thyroid rumours such as a mass in the neck, trouble swallowing, shortness of breath and persistent hoarseness.

Metformin is typically well tolerated. The most common side effects are nausea, abdominal discomfort and diarrhea. These usually only occur initially and go away with time; these side effects can also be minimized by taking metformin with meals and starting at a lower dose and gradually increasing the dose. It may also cause metallic taste. If you have significant side effects, in consultation with your doctor, you can try to stop taking metformin and then start taking at a lower dose and slowly increase the dose. A very rare side-effect of metformin is lactic acidosis: Symptoms include nausea, vomiting, abdominal pain, malaise, difficulty breathing and drowsiness. Long term use of metformin may cause vitamin b12 deficiency: low levels of vitamin B12 in your body.

Rybelsus vs Metformin: What are the advantages?

Rybelsus may help with weight loss. In a 6 month trial, patients taking Rybelsus 14 mg dose lost an average of 8 lbs and patients taking 7 mg dose lost an average of 5 pounds. [Ref]

Metformin does not cause hypoglycemia (dangerously low blood sugar levels in the blood) when used alone. It has a neutral effect on your weight and you may even have minor weight loss. It may also be used along with insulin treatment as it increases your body’s sensitivity to insulin and allowing a lower dose of insulin to be used. 

Sick day management

If you are experiencing an acute illness and are at risk of dehydration such as due to vomiting, diarrhea, fever, excessive heat exposure and the symptoms last for than 24 hours. some of your diabetes and other medications should be temporarily held. Read more here on Diabetes Canada website.

There is no current guidance for sick day management for Rybelsus.

Metformin should be temporarily held while you have an acute illness as described above.

Rybelsus vs Metformin: Is it safe for pregnancy and breastfeeding?

It is not currently known if Rybelsus is safe to take during pregnancy. It should be stopped 2 months prior to becoming pregnant.

It is not currently known if Rybelsus passes into breast milk. It is not recommended while breast feeding due to known risks.

Metformin is generally not recommended during pregnancy; insulin is the treatment of choice. Animal and human data suggest metformin is low risk in pregnancy.

Metformin passes into breast milk in relatively low amounts. Metformin is considered to be compatible with breastfeeding. Decision whether to breastfeed while on metformin should be made while considering the risk and benefits in consultation with your doctor. [Ref][Ref]

Other information to know

Rybelsus, also known by its generic name semaglutide is also available as a once weekly subcutaneous injection (Ozempic). Wegovy (injectable semaglutide), Saxenda (liraglutide) has also been approved as a weight loss treatment.

If you are undergoing an imaging test with contrast dye, metformin is recommended to be held for 2-3 days afterward; please consult with your doctor if this is necessary for the imaging test you are undergoing. Metformin is also recommended to be temporarily held on the day of surgery, please consult with your surgical team. 

Infertile women with polycystic ovary syndrome (which is associated with insulin resistance) who receive metformin may experience a resumption of ovulation.

Disclaimer: We have made every effort to ensure that all information is factually correct and up to date, however this article is not comprehensive and does not contain all relevant information about the topic. IT should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should consult your doctor or pharmacist before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

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