Rybelsus vs. Trulicity for Type 2 Diabetes: 4 Differences to Consider

Managing Type 2 diabetes often involves choosing between medications that work in similar ways. Rybelsus (semaglutide) and Trulicity (dulaglutide) are two popular options. Both belong to the same class — glucagon-like peptide-1 (GLP-1) receptor agonists — but they have key differences to consider.

If you don’t mind giving yourself injections, Trulicity can be a good choice. But if you want a needle-free alternative, Rybelsus could be the way to go. Curious how these medications compare? Here’s what you should know.

Rybelsus and Trulicity comparison summary

Both Rybelsus and Trulicity are GLP-1 receptor agonists used to treat Type 2 diabetes. But they differ in their dosage forms and approved uses, as well as how they’re regulated by the FDA. Before getting into the details, here’s a quick comparison:

Below, we take a closer look at five differences between Rybelsus and Trulicity to consider.

1. Rybelsus is taken by mouth, while Trulicity is an injection

The most noticeable difference between Rybelsus and Trulicity is their dosage forms. Rybelsus is the first and only GLP-1 medication available as a tablet. Trulicity is administered as a once-weekly injection under the skin. In this case, the best option can depend on your preference.

If you prefer to stick with pills, Rybelsus can be a more appealing option. However, it has specific instructions to follow so that your body properly absorbs your dose. You’ll need to take Rybelsus first thing in the morning on an empty stomach, with no more than 4 oz (120 mL) of plain water. You’ll also need to wait at least 30 minutes before eating, drinking, or taking anything else.

Trulicity is injected using a prefilled, single-use injection pen. You can inject it at home into your stomach, thigh, or upper arm. But if you choose the upper arm, it’s best to have someone else give you the injection since that area can be harder to reach.

2. Rybelsus and Trulicity have different dosage schedules

Rybelsus is taken once daily, while Trulicity is injected once weekly. This means that with Trulicity, you don’t need to remember to administer a dose every day — just once a week on the same day.

Rybelsus needs to be taken consistently each day, following the instructions described above. The active ingredient, semaglutide, isn’t absorbed very well when taken by mouth. The daily dosage schedule allows enough of the medication to build up in your body over time.

Trulicity may offer more flexibility for people who don’t want to worry about daily doses. In contrast, Rybelsus could be a better fit if you like consistency and can stick to a morning routine.

3. Rybelsus and Trulicity have different handling and storage requirements

Another key difference between Rybelsus and Trulicity is how they’re stored. Rybelsus is stored at room temperature, while Trulicity pens last longest if you keep them in the refrigerator.

When storing Rybelsus, avoid spots with fluctuating temperature and humidity, such as your car or bathroom cabinet. Keep the tablets in their original bottle — don’t store them in a pill organizer or other container.

Each Trulicity pen is used once before being thrown away. But until you inject your dose, you’ll need to store the pens properly. When stored in the refrigerator (between 36°F and 46°F), Trulicity pens will last until the expiration date on the label. If needed, you can keep them at room temperature (up to 86°F) for up to 14 days.

If you travel often or don’t have easy access to refrigeration, Rybelsus may be more convenient. On the other hand, Trulicity can still be manageable with proper planning if a once-weekly injection better suits your lifestyle.

4. Rybelsus is a peptide, and Trulicity is a biologic

Even though they’re both GLP-1 receptor agonists, Rybelsus and Trulicity differ in how they’re categorized. This can affect how they’re regulated and what lower-cost versions may become available in the future.

• Rybelsus: Rybelsus is made up of 31 amino acids (protein building blocks), which classifies it as a peptide. Peptides are short chains of amino acids (typically fewer than 40), and they’re approved and regulated like traditional medications.

• Trulicity: Because of its size and how it’s made, the FDA considers Trulicity to be a biologic. Because biologics are more complex, they have their own specific approval pathway.

So, why does this matter? Since it’s a peptide, generic versions of Rybelsus may be available down the road. Biologics such as Trulicity won’t have generics. Instead, Trulicity may have biosimilars, which are highly similar versions. Compared with generics, it can take longer for biosimilars to get to market.

Can you take Rybelsus and Trulicity together?

No, Rybelsus and Trulicity should not be taken together. They belong to the same GLP-1 class and work the same way in the body. Taking both can raise the risk of side effects such as nausea, vomiting, and low blood glucose (sugar).

If your current medication isn’t working well for you, your healthcare team can help you switch to a different option. But using Rybelsus and Trulicity together isn’t recommended.

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

Yes, switching between Rybelsus and Trulicity is possible.

You may be interested in switching GLP-1 medications if you’re not seeing results or are experiencing side effects or looking for a different dosage form. But it’s important to note that an injectable form of semaglutide (Ozempic) is also available. Depending on your situation, your prescriber may recommend switching to Ozempic instead.

How to save on Rybelsus and Trulicity

There are ways to save on Rybelsus and Trulicity, which are available as brand-name medications. Manufacturer copay savings cards, patient assistance programs, and GoodRx coupons can help make your prescription more affordable:

• Save with manufacturer copay savings cards. If you have commercial insurance, you could pay as little as $25 for Rybelsus or $25 for Trulicity with a copay savings card.

• Save with patient assistance programs. If you’re eligible, you could access Rybelsus or Trulicity for $0 through a patient assistance program.

• Save with GoodRx coupons: With GoodRx, you could save 14% off the average retail price of Rybelsus or 10% off the average retail price of Trulicity.

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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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