Rybelsus vs Trulicity

Trulicity and Rybelsus are two of the leading medications used to treat type 2 diabetes. Both belong to the GLP-1 receptor agonist class, which helps lower blood sugar levels and promote healthy weight loss. Yet, their differences in dosing, administration, and side-effect profiles can make one more suitable than the other for certain individuals.

In this article, we’ll look at how Trulicity and Rybelsus compare so you can better understand which might work best for you.

Which is more effective, Rybelsus or Trulicity?

Several studies have compared Rybelsus and Trulicity. Here’s a summary of the study’s outcomes:

For Type 2 Diabetes

In the PIONEER 10 study, researchers compared Rybelsus (oral semaglutide) and Trulicity (dulaglutide) in Japanese adults with type 2 diabetes. Participants were randomly assigned to one of the following treatments for 52 weeks:

• • Rybelsus 3 mg once daily
  • Rybelsus 7 mg once daily
  • Rybelsus 14 mg once daily
  • Trulicity 0.75 mg once weekly (injection)

After one year, Rybelsus 14 mg lowered average blood sugar (HbA1c) by about 1.7%, slightly more than Trulicity, which lowered it by 1.4%.

However, the Trulicity dose used in this study (0.75 mg) is the standard starting dose, considered a non-therapeutic dose in most clinical trials. Because of this, it’s difficult to tell whether Rybelsus is truly more effective overall, since higher doses of Trulicity have shown stronger results in other studies.

For example, in a separate phase 3 trial involving more than 1,800 adults with type 2 diabetes who were taking metformin, Trulicity 4.5 mg lowered HbA1c by about 1.8-1.9% after 36 weeks.

These results suggest that when used at higher, therapeutic doses, Trulicity’s efficacy becomes much closer to, or sometimes overlaps with, Rybelsus’ performance.

A follow-up analysis from PIONEER 10 also looked at quality of life. After 52 weeks, people taking Rybelsus 7 mg or 14 mg reported greater improvements in well-being than those using Trulicity 0.75 mg.

Participants on oral semaglutide felt less anxious and more satisfied with their daily treatment routine, and most said the medication did not interfere with their work or social life. Both treatments caused little concern about low blood sugar, but Rybelsus users experienced more sustained improvements in quality of life over the study period.

For Weight Loss

In the PIONEER 10 study, people taking Rybelsus lost weight in a dose-dependent way:

• • 3 mg: no change
  • 7 mg: lost about 0.9 kg (2 lbs)
  • 14 mg: lost about 1.6 kg (3.5 lbs)

Meanwhile, those on Trulicity gained about 1 kg (2 lbs). By week 52, people taking the highest Rybelsus dose weighed about 2.6 kg (6 lbs) less than those on Trulicity.

However, this study used the lower, 0.75 mg dose of Trulicity, which isn’t the full therapeutic dose. In Trulicity’s own trials, participants on the higher 4.5 mg dose lost about 4-5 kg (9-11 lbs) after 36 weeks.

In a real-world study comparing both drugs, Rybelsus again showed stronger results and 61% of users lost at least 5% of their body weight, compared with 41% of those on Trulicity. On average, participants lost about 5 kg (11 lbs) and saw significant improvements in BMI and HbA1c levels.

For Reducing the Risk of MACE

People with type 2 diabetes have a much higher risk of heart disease, stroke, and other cardiovascular problems. GLP-1 receptor agonists like semaglutide and dulaglutide not only help lower blood sugar and support weight loss, but they may also protect the heart.

While there haven’t been direct head-to-head studies, clinical trials on both Rybelsus and Trulicity have shown heart-protective effects.

In the PIONEER 6 trial, participants taking Rybelsus had notably better cardiovascular outcomes compared to those on a placebo:

• • Major heart-related events were reduced by about 21%
  • Deaths from heart disease dropped by roughly 53%
  • The overall death rate fell by 50%
  • Stroke risk decreased by around 20%

Meanwhile, in the REWIND trial, Trulicity (1.5 mg weekly) lowered the risk of major cardiovascular events by 12% versus placebo. A subgroup analysis also confirmed that Trulicity was equally effective and safe across all age groups, including adults 65 and older.

Which causes more side effects?

In the PIONEER 10 trial, side effects occurred in 77-85% of Rybelsus users and 82% of Trulicity users. The most common were mild stomach issues like nausea and constipation, along with infections. About 3-6% of participants stopped treatment early because of side effects, which was similar for both drugs. No severe low blood sugar was reported.

Both drugs have also been tested for safety in their clinical trials. Here’s a summary of the results:

They also share similar risks, which include the following:

• • Thyroid C-Cell tumors
  • Pancreatitis
  • Complications of diabetic retinopathy
  • Hypoglycemia (especially when combined with insulin or insulin secretagogues)
  • Acute kidney injury
  • Hypersensitivity reactions
  • Acute gallbladder disease
  • Pulmonary aspiration (noted during general anesthesia or deep sedation)

Talk openly with your doctor so you can manage any side effects safely.

How do Rybelsus and Trulicity work?

Rybelsus (semaglutide) and Trulicity (dulaglutide) both mimic a natural hormone called GLP-1, which helps regulate blood sugar and appetite. These drugs activate GLP-1 receptors found in the pancreas and stomach, helping the body control blood sugar more efficiently.

In the pancreas, they boost insulin release only when blood sugar is high, lowering glucose levels without causing dangerous drops. They also reduce glucagon secretion, preventing the liver from making excess sugar.

In the stomach, they slow digestion to prevent blood sugar spikes after eating. They also curb appetite, which can further support weight loss and blood sugar control.

Although Rybelsus and Trulicity work in similar ways, they differ in how the body absorbs and processes them. Because Rybelsus is taken orally, it has much lower bioavailability than Trulicity, which is given as an injection.

For Rybelsus, the estimated absolute bioavailability was about:

• • 0.4-1% after oral doses of 3 mg, 7 mg, or 14 mg (formulation R1)
  • 1-2% after oral doses of 1.5 mg, 4 mg, or 9 mg (formulation R2)

For Trulicity, the mean absolute bioavailability after a subcutaneous injection was:

• • 65% for the 0.75 mg dose
  • 47% for the 1.5 mg dose

Bioavailability for higher Trulicity doses (3 mg and 4.5 mg) was estimated to be similar to the 1.5 mg dose, though not specifically studied. Trulicity concentrations also increased proportionally with the dose from 0.75 mg to 4.5 mg.

What are they used for?

For type 2 diabetes, Rybelsus is approved for adults as an add-on to diet and exercise to help improve blood sugar control. Trulicity is approved for the same use in adults and also in children aged 10 years and older.

Both medications are also indicated for adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors to help reduce the risk of major cardiovascular events, such as heart attack and stroke.

How are Rybelsus and Trulicity dosed?

Trulicity is injected once weekly. Treatment begins with 0.75 mg once a week for the first four weeks, then increases to 1.5 mg weekly for at least the next four weeks. If additional blood sugar control is needed, the dose may be increased in 1.5 mg steps after at least four weeks on the current level, up to a maximum of 4.5 mg once weekly.

For pediatric patients, the recommended starting dosage of Trulicity is also 0.75 mg once weekly. However, the maximum dose is only 1.5 mg once weekly. This adjustment should only be considered after at least four weeks on the 0.75 mg dose.

On the other hand, Rybelsus is taken by mouth once daily in the morning on an empty stomach with no more than 4 ounces (about half a cup) of water.

After swallowing the tablet, you have to wait at least 30 minutes before eating, drinking, or taking any other medications. The tablet should be swallowed whole, not split, crushed, or chewed.

Here is the typical Rybelsus dosing schedule:

Cost of Rybelsus vs. Trulicity

Rybelsus costs $997.58 per month, while Trulicity costs $987.19 per month. Paying out of pocket for these diabetes medications can be very costly.

Pharma Giant provides a lower-cost and convenient alternative for getting these treatments. As a licensed Canadian pharmacy partner, Pharma Giant offers safe, verified medications at prices often below US retail costs, with direct home delivery for added convenience.

Here’s a look at the pricing and savings with Rybelsus from Pharma Giant:

Here’s a look at the pricing and savings with Trulicity from Pharma Giant:

You can save even more with our Trulicity coupons and Rybelsus coupons, and as a new customer, you’ll get an extra 10% off with the code PGSAVE10.

Wrap-up

Both Rybelsus and Trulicity are effective for controlling blood sugar, supporting weight loss, and protecting heart health in people with type 2 diabetes. Side effects are mostly mild stomach issues and occur at similar rates. The main difference lies in how they’re taken. Rybelsus is a daily pill, while Trulicity is a weekly injection.

If you prefer convenience and fewer doses, Trulicity may be easier to manage. If you want an oral option with strong results, Rybelsus is a good choice.

Frequently Asked Questions

Sources

Yabe, D., Nakamura, J., Kaneto, H., Deenadayalan, S., Navarria, A., Gislum, M., Inagaki, N., Arisaka, T., Asakura, T., Azuma, N., Fukuda, S., Fukushima, Y., Harada, N., Inoue, S., Ishida, H., Ishii, H., Ishikawa, S., Jinnouchi, H., Kaneko, S., . . . Yamauchi, A. (2020). Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. The Lancet Diabetes & Endocrinology, 8(5), 392–406. https://doi.org/10.1016/s2213-8587(20)30074-7

Ishii, H., Hansen, B. B., Langer, J., & Horio, H. (2021). Effect of Orally Administered Semaglutide Versus Dulaglutide on Diabetes-Related Quality of Life in Japanese Patients with Type 2 Diabetes: The PIONEER 10 Randomized, Active-Controlled Trial. Diabetes Therapy, 12(2), 613–623. https://doi.org/10.1007/s13300-020-00985-w

Frias, J. P., Bonora, E., Ruiz, L. N., Li, Y. G., Yu, Z., Milicevic, Z., Malik, R., Bethel, M. A., & Cox, D. A. (2021). Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11). Diabetes Care, 44(3), 765–773. https://doi.org/10.2337/dc20-1473

Seijas-Amigo, J., Salgado-Barreira, Á., Castelo-Dominguez, R., Pérez-Álvarez, M. T., Ponce-Piñón, B., Fernández-Silva, M., Rodríguez-Barreiro, M., Pereira-Pía, M., Iglesias-Moreno, J. M., Gago-García, M., Montáns-García, R., Fernandez-Perez, A., FragaGayoso, D., Fernandez-Montenegro, M., Riveiro-Barciela, B., Rilla-Villar, N., Cordero, A., RodríguezMañero, M., & González-Juanatey, J. R. (2023). Differences in weight loss and safety between the glucagon-like peptide-1 receptor agonists: A non-randomized multicenter study from the titration phase. Primary Care Diabetes, 17(4), 366–372. https://doi.org/10.1016/j.pcd.2023.05.004

Husain, M., Birkenfeld, A. L., Donsmark, M., Dungan, K., Eliaschewitz, F. G., Franco, D. R., Jeppesen, O. K., Lingvay, I., Mosenzon, O., Pedersen, S. D., Tack, C. J., Thomsen, M., Vilsbøll, T., Warren, M. L., & Bain, S. C. (2019). Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine, 381(9), 841–851. https://doi.org/10.1056/nejmoa1901118

Riddle, M. C., Gerstein, H. C., Xavier, D., Cushman, W. C., Leiter, L. A., Raubenheimer, P. J., Atisso, C. M., Raha, S., Varnado, O. J., Konig, M., Lakshmanan, M., & Franek, E. (2021). Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trial. The Journal of Clinical Endocrinology & Metabolism, 106(5), 1345–1351. https://doi.org/10.1210/clinem/dgab065

Gerstein, H. C., Colhoun, H. M., Dagenais, G. R., Diaz, R., Lakshmanan, M., Pais, P., Probstfield, J., Riesmeyer, J. S., Riddle, M. C., Rydén, L., Xavier, D., Atisso, C. M., Dyal, L., Hall, S., Rao-Melacini, P., Wong, G., Avezum, A., Basile, J., Chung, N., . . . Zigrang, W. (2019). Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet, 394(10193), 121–130. https://doi.org/10.1016/s0140-6736(19)31149-3

Trulicity Cost Information | With or Without Insurance | Trulicity® (dulaglutide) injection. (n.d.). https://pricinginfo.lilly.com/Trulicity

RYBELSUS® (semaglutide) tablets 7 mg or 14 mg List Price & Insurance Coverage Explained | NovoCare®. (n.d.). https://www.novocare.com/diabetes/products/rybelsus/explaining-list-price.html