What is the difference between Rybelsus and Mounjaro?

When it comes to medications for managing type 2 diabetes, you have options — two of which are Rybelsus and Mounjaro. Comparing them isn’t necessarily an apples and oranges thing…it’s more apples and apple juice. Yes, they have a lot of similarities, but there are some key differences as well. Keep reading to learn more about Rybelsus versus Mounjaro, including how each works, effectiveness, side effects, and more. With this information (and the guidance of a healthcare practitioner) you'll be well-equipped to make an educated decision about what is best for you.

What is Rybelsus?

Rybelsus is an oral version of semaglutide, which belongs to a class of drugs called glucagon-like peptide 1 receptor agonists (GLP-1s). Taken as a pill once daily, it’s designed to help adults with type 2 diabetes regulate their blood sugar levels. By mimicking the naturally occurring GLP-1 you have in your body, Rybelsus stimulates the release of insulin when blood sugar is high and decreases the release of sugar from the liver, two actions that help regulate your blood sugar. It also helps reduce your appetite and slows the emptying of food from your stomach, so you stay full for longer, potentially leading to weight loss.

What is Mounjaro?

Mounjaro is the brand name of tirzepatide, which is also approved by the F.D.A. for controlling blood sugar in adults with type 2 diabetes. It’s a once-weekly injection that works by mimicking two hormones in your body: GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). These two hormones work together — the GIP amplifies the impact of the GLP-1 — to help your body bring down blood sugar (by releasing insulin), reduce appetite, and slow down digestion. The result is improved glucose control and, similar to Rybelsus, weight loss.

Key differences between Mounjaro and Rybelsus

The two main differences between Mounjaro and Rybelsus are their active ingredients and the way they’re administered. “Rybelsus is oral semaglutide, while Mounjaro is injectable tirzepatide,” states Dr. Priya Jaisinghani, M.D., a specialist in endocrinology, obesity medicine, and diabetes at NYU Langone Health. Additionally, the two medications aren’t taken with the same frequency: Rybelsus is once a day and Mounjaro is once a week.

Rybelsus and Mounjaro approved uses

Rybelsus and Mounjaro are both F.D.A.-approved for the treatment of type 2 diabetes in adults aged 18 and over. They help control blood sugar by mimicking naturally occurring hormones in your body: Rybelsus mimics GLP-1, while Mounjaro mimics GLP-1 and GIP. These medications improve insulin production, slow digestion, reduce blood sugar release from the liver, and decrease appetite. Jaisinghani notes that both medications should be used alongside lifestyle changes, like diet and exercise, in order to have the biggest impact on your health.

There is an injectable form of semaglutide, the active ingredient in Rybelsus, approved for type 2 diabetes: Ozempic. And both semaglutide and tirzepatide (the active ingredient in Mounjaro) have brands F.D.A.-approved for weight loss: Wegovy (semaglutide) and Zepbound (tirzepatide).

Rybelsus vs. Mounjaro dosages and administration

GLP-1 medications like Mounjaro and Rybelsus follow what’s known as a slow titration method when someone is first starting out on them. This means doses start small and increase slowly to allow the body to gradually adjust to the medication and minimize side effects.

Rybelsus is a once-daily pill that is taken by mouth. The starting dose for Rybelsus is generally 3 mg daily for 30 days, increasing to 7 mg daily for 30 days and, if necessary, going up to the maximum dosage of 14 mg daily. There are some “rules” around how to take Rybelsus — like that you have to take the pill in the morning at least 30 minutes before you eat or drink — that your prescriber will be able to go over with you.

Mounjaro is a once-weekly injection that can be administered into the thigh, abdomen, or upper arm. Mounjaro starts at 2.5 mg once weekly for the first 4 weeks, and is then slowly increased by 2.5mg every 4 weeks until your doctor is happy with your glucose control or you hit the maximum Mounjaro dosage of 15 mg. You can do the injection at any point in the day, but it can help to give it to yourself at the same time each week so that you don’t forget.

Effectiveness of Rybelsus vs. Mounjaro

Both Rybelsus and Mounjaro are effective at reducing A1c levels, which is a way to measure blood sugar over time. Research has shown that after six months, people on 7 mg of Rybelsus reduced their A1c by an average of 1.2% while those on 14 mg of the medication dropped their A1c by 1.4%.

Mounjaro has slightly better results. After nine months, patients on a 10 mg Mounjaro prescription reduced their A1c by 1.9%, and those taking 15 mg of it reduced their A1c by 2.1%. Keep in mind, though, that the effectiveness of any medication is truly dependent on the individual — one person might react better to Rybelsus while another to Mounjaro.

While glycemic control is the intended use of these medications, weight loss is often a common side effect. People on 15 mg of Mounjaro could lose an average of 20.9% of their body weight in a little more than a year, while Rybelsus has less of an impact. One study found that people taking Rybelsus lost about 4% of their body weight after taking a 14 mg Rybelsus prescription for a year.

Dr. Meghan Garcia-Webb, M.D., a triple board-certified physician in internal medicine, lifestyle medicine, and obesity medicine, confirms this conclusion. “Mounjaro tends to be much more effective for weight loss than Rybelsus,” she says. “There’s always the outlier patient who does lose weight on Rybelsus, but if given the choice, I’ll choose Mounjaro every time for weight loss.”

Rybelsus vs. Mounjaro cost and insurance coverage

GLP-1 weight-loss medications like Rybelsus and Mounjaro can be pretty expensive if you don’t have insurance. According to Eli Lilly, which manufactures Mounjaro, the list price (the original price set for a medication by a manufacturer before any discounts are applied) of Mounjaro is $1,079.77 per month. Novo Nordisk, the manufacturer of Rybelsus, lists the cost of Rybelsus at $997.58 per month.

If your healthcare provider prescribes Rybelsus or Mounjaro for its intended use of managing type 2 diabetes and you have health insurance, it’s likely to cover a large portion of the medication cost as long as you meet any prerequisites. However, if your provider prescribes either medication for weight loss, you may have to pay out of pocket as insurance companies are less likely to cover the cost of Mounjaro or Rybelsus when used off-label.

Keep in mind as well that there may be manufacturer’s savings programs that can help bring down your out-of-pocket cost. You can find information on these for Rybelsus here and Mounjaro here.

Rybelsus vs. Mounjaro side effects

While these medications can have significant effects on your blood sugar control and ability to lose weight, they may cause uncomfortable side effects — especially when first starting on the medication or increasing the dosage. And because the common side effects tend to be gastrointestinal, like nausea and diarrhea, Jaisinghani says they can be made worse by certain behaviors. “Eating rapidly, consuming large meals, or fatty, greasy foods can exacerbate these symptoms.” Since making certain changes to your diet can help manage these side effects, pairing these medications with a lifestyle program like WeightWatchers, which includes visits with registered dietitians, can be helpful.

Rybelsus side effects

The most common side effects of Rybelsus include stomach pain, nausea, diarrhea, vomiting, constipation, and decreased appetite. Other serious side effects to be aware of include pancreatitis, changes in vision, low blood sugar (when combined with other diabetes medications), kidney problems, severe stomach problems, allergic reactions, and gallbladder problems. Find a full list of Rybelsus side effects here.

Mounjaro side effects

Common side effects of Mounjaro are similar to those of Rybelsus. They include nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion, and stomach pain. More rare but serious side effects include kidney problems, severe stomach problems, pancreatitis, low blood sugar (when combined with other diabetes medications), allergic reactions, changes in vision, and gallbladder problems. You can see the full list of Mounjaro’s side effects here.

Rybelsus and Mounjaro drug warnings

While generally considered safe medications, both Rybelsus and Mounjaro feature the same black-box warning (the F.D.A.’s most serious warning label) of a risk of thyroid C-cell tumors, including medullary thyroid carcinoma (MTC). While that sounds scary, the warning is based on rat studies, and there haven’t been any studies determining the risk in humans. They should also not be used in patients with a personal or family history of MTC or who have multiple endocrine neoplasia syndrome type 2 (MEN 2).

There are also the more serious side effects noted above. “In rare cases, each [medication] carries the risk of gallbladder issues, pancreatitis, exaggerated gastroparesis, bowel obstruction, and mood changes,” says Garcia-Webb. “Semaglutide may also have an increased risk of non-arteritic anterior ischemic optic neuropathy (NAION), which is an optic nerve disorder that can cause significant vision issues.” That said, the risk that any of these occur are quite low and has not been proven yet in other studies. For context, less than 1% of patients in the placebo-controlled clinical trials for each drug reported gallbladder issues.

The bottom line

Rybelsus and Mounjaro are both GLP-1 agonists F.D.A.-approved to treat type 2 diabetes in adults, but they have some key differences. Rybelsus (semaglutide) is a daily oral weight-loss medication that contains only GLP-1 hormone, whereas Mounjaro (tirzepatide) is a once-weekly injection featuring GLP-1 and GIP hormones. Rybelsus and Mounjaro both have similar side effects, which tend to impact the gastrointestinal system. Research suggests that both medications promote blood sugar control and weight loss; however, Mounjaro may produce more significant results.