Mounjaro vs. Rybelsus: 5 Differences for Type 2 Diabetes

If you’re living with Type 2 diabetes, there are many oral and injectable medications available to help you meet your treatment goals. Of these, Mounjaro (tirzepatide) and Rybelsus (semaglutide) are two options your prescriber may recommend.

Mounjaro and Rybelsus may seem similar, but there are a few key differences between them. For example, are you OK with giving yourself injections, or do you prefer an oral pill? Your answer may lead you to pick one over the other. Below, we cover five differences between Mounjaro and Rybelsus to consider.

1. Mounjaro is an injection, while Rybelsus is an oral pill

One key difference between Mounjaro and Rybelsus is their dosage forms. Mounjaro is available as a subcutaneous (under the skin) injection, while Rybelsus is an oral pill. In fact, Rybelsus is the only medication in its class that isn’t injected.

Mounjaro comes in a prefilled injection pen. Each pen contains 1 dose, meaning that you’ll throw the pen away into a sharps container after injecting your dose. You can inject Mounjaro anytime of day, with or without food. Unused Mounjaro pens last longer if you keep them in the refrigerator.

Rybelsus comes in a tablet that you take by mouth. Swallow the tablets whole — don’t cut, crush, or chew them. Take Rybelsus first thing in the morning on an empty stomach, with no more than 4 oz (120 mL) of water. Don’t eat, drink other liquids, or take other medications for at least 30 minutes. Keep the tablets in their original container to protect them from moisture.

Semaglutide, the active ingredient in Rybelsus, is also available as an injection called Ozempic. If you have difficulty timing Rybelsus around meals and medications, Ozempic may be an option to consider.

2. Rybelsus needs to be taken more frequently than Mounjaro

Mounjaro and Rybelsus both last a long time in the body. But Mounjaro is injected once a week, and Rybelsus is taken once a day. This is because there are differences in how the body absorbs the injection compared with the pill.

After you inject Mounjaro, your body absorbs about 80% of your dose. And it takes a little less than 1 week for your body to remove half of it. Because of this, Mounjaro needs to be injected only once a week. This weekly dosage allows for consistent levels of Mounjaro in the body.

With Rybelsus, your body absorbs a much smaller amount of your dose — less than 1%. This is because enzymes (proteins) and high acidity in the gut break it down. But it still takes about 1 week for your body to remove half of it. Taking Rybelsus every day allows these small amounts to build up, resulting in consistent levels over time.

3. Mounjaro and Rybelsus work in similar but slightly different ways

Mounjaro and Rybelsus both work by simulating the effects of gut hormones called incretins. Your body releases incretins after you eat. They play a role in regulating blood glucose (sugar) levels, digestion, and appetite. But Rybelsus simulates one incretin, while Mounjaro simulates two incretins.

Rybelsus is a glucagon-like peptide-1 (GLP-1) receptor agonist. It simulates an incretin called GLP-1, which has the following key effects in the body:

• Triggers insulin release after meals

• Slows movement of food out of the stomach

• Reduces how much sugar the liver makes

• Works in the brain to lessen appetite and cravings

Mounjaro belongs to a medication class called dual glucose-dependent insulinotropic polypeptide (GIP) / GLP-1 agonists. It simulates the effects of GLP-1 and GIP, which is another gut hormone. GIP is thought to work synergistically with GLP-1 in some aspects, resulting in more potent effects on blood sugar and body weight.

4. Mounjaro may lower A1C more than Rybelsus

Hemoglobin A1C (HbA1C or A1C) is a test that measures your average blood sugar levels over the last 3 months. Having an A1C below 7% is a common goal for most people with diabetes. Compared with Rybelsus, Mounjaro may have a greater impact on A1C.

Mounjaro and Rybelsus haven’t been compared directly in clinical studies. But Mounjaro has been compared with Ozempic, the injectable form of Rybelsus. During a 40-week study, the highest Mounjaro dose (15 mg) lowered A1C by 2.3%. This was compared with a 1.86% reduction with Ozempic (1 mg dose). During a more recent clinical trial, the highest Rybelsus dose (14 mg) lowered A1C by about 1.5% over 52 weeks.

The highest Rybelsus dose is 14 mg. Higher doses (25 mg and 50 mg) may be available in the future. These doses have been shown to lower A1C up to about 2%.

5. Mounjaro may result in greater weight loss than Rybelsus

Mounjaro and Rybelsus aren’t approved for weight loss. But people using them tend to lose weight. In fact, their active ingredients are found in the weight-loss medications Zepbound (tirzepatide) and Wegovy (semaglutide). Because of how Mounjaro works, it may result in greater weight loss than Rybelsus.

During clinical trials, people receiving Mounjaro lost 15 to 20 lbs over 40 weeks. With Rybelsus, people taking the highest dose lost almost 10 lbs over 52 weeks. Mounjaro and Rybelsus haven’t been studied directly. But the same comparison trial with Ozempic showed greater weight loss with Mounjaro.

Higher Rybelsus doses that are being studied have resulted in greater weight loss than the 14 mg dose. At 52 weeks, people taking the 25 mg dose lost almost 15 lbs, and those taking the 50 mg dose lost almost 18 lbs.

Keep in mind: If you’re prescribed Mounjaro or Rybelsus for weight loss and you don’t have diabetes, this is considered an off-label use. That’s because Mounjaro and Rybelsus are approved only for people with Type 2 diabetes.

Can you switch from Rybelsus to Mounjaro (or vice versa)?

Yes, it’s possible to switch from Rybelsus to Mounjaro. But there isn’t a specific dose-conversion chart to switch between medications. So your prescriber may have you start with a low Mounjaro dose and work your way up. This can help you find your optimal dose while managing side effects.

Since Mounjaro tends to have a greater impact on A1C and body weight, your prescriber may not consider Rybelsus if Mounjaro isn’t working well enough for you. If you need more help lowering your A1C, they may add another medication to your treatment plan.

That said, Rybelsus is also approved to lower the risk of major cardiovascular events (heart attack, stroke, or cardiovascular death) in adults with Type 2 diabetes at high risk for these events. Mounjaro doesn't have this approval yet. Depending on your medical history and risk factors, your prescriber may decide that Rybelsus is a better fit.

Can you take Rybelsus and Mounjaro together?

No. Since Rybelsus and Mounjaro work in a similar way, you’ll be prescribed one or the other — not both. Your prescriber may consider switching you to Mounjaro if Rybelsus isn’t working well enough. Or they may add other medications to your treatment plan.

How to save on Mounjaro and Rybelsus

Mounjaro and Rybelsus are both available as brand-name medications. No matter which medication you’re prescribed, GoodRx can help you find ways to make your prescription more affordable.

If you’re eligible, you could pay as little as $25 for Mounjaro or $10 for Rybelsus with a manufacturer copay card. Or you may qualify to get Rybelsus at no charge through the manufacturer’s patient assistance program. Keep in mind that you may need a Type 2 diabetes diagnosis to qualify for these programs.

With a free GoodRx coupon, you could save over 10% off the average retail price at certain pharmacies.

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Written by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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