Rybelsus vs Trulicity: Benefits, Similarities, Differences

If you have type 2 diabetes, you’re probably aware of the increasing number of medications on the market to help you control your blood sugar. 

The Food and Drug Administration has approved several new diabetes medications in the last decade, including Rybelsus and Trulicity.

These two medications share the same drug class, but they are also different in several ways. 

How do Rybelsus and Trulicity stack up against each other? 

Take a look at our in-depth comparison of Rybelsus vs Trulicity.

What is Trulicity?

Trulicity is the brand name for a GLP-1 receptor agonist called dulaglutide. The FDA approved Trulicity to treat type 2 diabetes in September 2014 and again in February 2020 to reduce cardiovascular events in people with and without heart disease.

GLP-1 receptors in your pancreas help increase insulin secretion while reducing glucagon secretion. Glucagon is a hormone that raises blood sugar levels. 

GLP-1 receptor agonists activate these receptors to help your body produce its own insulin to lower your blood sugar.

GLP-1 receptor agonists like Trulicity can also promote weight loss because they help reduce appetite and promote fullness by slowing stomach emptying (1, 2). Delayed stomach emptying can also help promote more stable blood sugar levels. 

Most of the GLP-1 receptor agonists are injectable (except Rybelsus). Trulicity comes in a prefilled injector pen with typical dosages ranging from 0.75-4.5 milligrams weekly.

While taking this medication, you may wish to adjust your diet in order to maximize your results and reduce the chance of side effects. Some foods to avoid while taking Trulicity include fried foods, foods with added sugar, and refined grains.

What is Rybelsus?

Rybelsus is the brand name for oral semaglutide, a GLP-1 receptor agonist. Rybelsus is unique because it is currently the only oral GLP-1 receptor agonist on the market. The injectable form of semaglutide is Ozempic (see Rybelsus vs Ozempic for more info).

Rybelsus is one of the newer type 2 diabetes medications, and the Food and Drug Administration (FDA) approved it in 2019. 

Rybelsus comes in 3-, 7-, and 14-milligram tablets. The 3-milligram dosing is only used to initiate treatment and isn’t typically a therapeutic or maintenance dose.

The dosing for Rybelsus is usually as follows:

• Start taking Rybelsus at a dose of 3 milligrams daily for 30 days.
• After taking the 3-milligram dose for 30 days, increase your dose to 7 milligrams daily.
• If you’re not meeting your blood sugar targets after 30 days on the 7-milligram dose, increase your Rybelsus dose to 14 milligrams daily, which is the maximum dose.

While taking this medication, you may wish to adjust your diet in order to maximize your results and reduce the chance of side effects. Some foods to avoid while taking Rybelsus include high-fat foods, spicy foods, and refined carbs.

Are Rybelsus and Trulicity the same thing?

Rybelsus and Trulicity are both GLP-1 receptor agonists, but they aren’t the same drug. Rybelsus’s drug name is semaglutide, and Trulicity’s drug name is dulaglutide. Rybelsus is an oral medication, while Trulicity is an injectable.

Because they are in the same drug class, Rybelsus and Trulicity work in similar ways and have similar side effects and precautions. 

Trulicity vs Rybelsus effectiveness for diabetes

Trulicity

A 40-week clinical trial assessed the effectiveness of Trulicity for diabetes (along with Ozempic, another injectable GLP-1 receptor agonist). 

1,201 patients with type 2 diabetes who were at least 18 years old were included in the study. Participants’ blood sugar levels were previously uncontrolled on metformin (an oral diabetes medication) alone, with their A1cs ranging from 7-10.5%.

The group receiving 0.75 milligrams weekly of Trulicity had their A1c levels reduced by an average of 1.1% compared to their baseline. 

The reduction in blood sugar levels was more drastic when the dosage of Trulicity was increased. The participants receiving 1.5 milligrams of Trulicity had an average reduction in A1c of 1.3% compared to 1.1% on 0.75 milligrams.

According to a 52-week clinical trial, when the dose of Trulicity is increased to 3 milligrams weekly, the average reduction in A1c jumps to 1.6% and 1.8% with 4.5 milligrams weekly. These results are based on a 36-week trial with a mean baseline A1c of 8.6% who were already taking metformin.

Rybelsus

According to a six-month clinical trial, taking 7 milligrams of Rybelsus resulted in a 1.2% reduction in hemoglobin A1c levels (average starting A1c was 8%).

With the same average starting A1c of 8%, taking 14 milligrams of Rybelsus resulted in a 1.4% reduction in hemoglobin A1c levels over the six-month study.

Bottom line: At their maximum doses in these studies, Rybelsus resulted in a 1.4% reduction in A1c (average starting A1c of 8%), and Trulicity reduced A1c by an average of 1.8% with an average starting A1c of 8.6%. Therefore, Rybelsus and Trulicity are similar in their effectiveness in lowering blood sugar levels.

Benefits of Trulicity vs Rybelsus

• Trulicity is FDA-approved to help reduce the risk of cardiovascular outcomes, while Rybelsus is currently not. However, according to a study, Rybelsus reduced the risk of heart-related death by 51% compared to a placebo.
• Trulicity’s ease of use (for those without a phobia of needles) is more convenient with weekly dosage vs Rybelsus’ daily dosing.
• Trulicity can be taken with or without food, while Rybelsus must be taken on an empty stomach to maximize its effectiveness.

What are the side effects of each medication?

Trulicity and Rybelsus have similar side effects because they are in the same drug class. Side effects are most common when you first start taking a new medication and when your dose is increased. 

Side effects usually dissipate as your body gets used to the medication, but some people have to discontinue medications if the side effects are too severe.

Trulicity

The most commonly reported side effects of Trulicity include:

• Nausea
• Diarrhea
• Vomiting
• Abdominal Pain
• Decreased appetite
• Indigestion
• Fatigue

Rybelsus

The most commonly reported side effects of Rybelsus include:

• Nausea
• Diarrhea
• Vomiting
• Stomach pain
• Decreased appetite
• Constipation

Rare but serious side effects

All GLP-1 receptor agonists come with rare but more serious potential complications. This includes thyroid cancer, gallbladder problems, pancreatitis, kidney problems, low blood sugar (not common unless you take them with insulin or sulfonylurea), and worsening diabetic retinopathy.

If you experience any of the following side effects, it could signify a more serious medical condition. 

Contact your healthcare provider right away if you experience:

• A lump or swelling in your neck (thyroid problems)
• Yellowing of the whites of your eyes and/or skin (gallbladder problems)
• Severe vomiting and diarrhea resulting in dehydration (can worsen kidney problems)
• Changes in your vision (retinopathy concerns)
• Severe abdominal pain (gallbladder problems, pancreatitis)

Which medication is cheaper?

According to GoodRx, the cost for a 30-day supply of 7-milligram tablets of Rybelsus will be in the range of $800-$900 out of pocket. 

Also according to GoodRx, four prefilled pens (around one month’s worth) containing 3 milligrams each of Trulicity cost around $770.

According to these calculations, Trulicity might be slightly cheaper, but it could be more expensive during the months when you need more than four pens based on how many weeks are in the month.

If you have prescription drug coverage or other forms of medical insurance, your cost for these medications will likely be different. If one of the drugs is preferred by your insurance provider, it will likely be much less expensive than the above out-of-pocket estimates.

Ease of use for Trulicity vs Rybelsus

The main differences in ease of use for Trulicity vs Rybelsus lie in their form (injectable vs oral) and frequency of dosing (weekly vs daily). 

If you don’t want to use injectable medications, Rybelsus might be easier for you to use than Trulicity because you take it orally. Remember that Rybelsus must be taken every day, at least 30 minutes before you eat or drink anything.

If you have a difficult time taking daily medications, then Trulicity might be the better option, though it does require a weekly injection. If you cannot administer your injections, then Rybelsus might be the better choice.

Rybelsus vs Trulicity for weight loss

Rybelsus and Trulicity can cause weight loss because they slow gastric emptying and can reduce appetite. When you first start taking either medication, you might experience nausea, vomiting, and other stomach symptoms, which can also result in weight loss.

Rybelsus

In a 52-week study on Rybelsus weight loss results, the average weight loss while taking Rybelsus (increased to the maximum dose of 14 milligrams) was around 4.4 kilograms. 

Patients in that study had already been taking metformin at a stable dose to treat their type 2 diabetes (3).

Trulicity

A study on Trulicity weight loss results administered Trulicity to participants at 1.5, 3.0, and 4.5 milligram weekly doses for 52 weeks (4). 

By week 36, the group receiving 1.5 milligrams of Trulicity lost an average of 3.1 kilograms (6.9 pounds), the group receiving 3 milligrams lost an average of 4 kilograms (8.8 pounds), and the group receiving 4 milligrams lost an average of 4.7 kilograms (10.3 pounds). The mean starting weight for all participants was around 211 pounds (96 kilograms).

These are just a few studies and don’t summarize everyone taking Rybelsus and Trulicity. It’s possible to lose more or less weight than these studies, or you might gain weight.

Comparing these studies and the maximum doses of each medication, Truclity and Rybelsus appear to provide similar weight loss outcomes (around ten pounds on average).

Rybelsus vs Trulicity for PCOS

Polycystic ovary syndrome (PCOS) is a hormonal condition that impacts hormone levels in women. PCOS typically causes high levels of androgens, a type of male sex hormone, resulting in infertility, unwanted hair growth, hair loss, acne, and other symptoms.

PCOS is often rooted in insulin resistance, meaning women with PCOS often have elevated blood sugar and insulin levels. Because GLP-1 receptor agonists like Rybelsus and Trulicity can improve insulin sensitivity and blood sugar levels, they might help treat PCOS.

Neither Rybelsus nor Trulicity is approved to treat PCOS at this time. However, studies note that GLP-1 receptor agonists are among many potential therapeutic options for treating PCOS (5).

In addition, a small clinical trial is underway to assess Rybelsus’ potential ability to treat PCOS. The estimated completion of the study is in 2024 (6).

Can you take Trulicity with Rybelsus?

You shouldn’t take Trulicity and Rybelsus together. Taking these medications together could increase your likelihood of side effects.

Trulicity and Rybelsus can be taken with some other diabetes medications under the guidance of your healthcare provider, such as metformin and insulin.

Natural alternatives to Trulicity and Rybelsus

Many people prefer to try natural alternatives instead of prescription medications. If you’re a good candidate to treat your diabetes more naturally, consider some of the following natural alternatives to Trulicity and Rybelsus.

Magnesium

According to large studies, low magnesium intake is associated with an increased risk of developing type 2 diabetes. 

Type 2 diabetes stems from insulin resistance, which is when your body doesn’t use the hormone insulin effectively, leading to higher blood sugar levels.

People with diabetes tend to have lower levels of magnesium in their blood compared to people without diabetes, which further strengthens the likely role that magnesium plays in diabetes.

If you don’t eat many magnesium-rich foods in your diet (leafy greens, nuts, seeds, whole grains, and beans are all good sources), magnesium supplementation can help improve insulin sensitivity (7).

You can find magnesium supplements at most stores and online. The most common dose of magnesium is 400 milligrams.

Berberine

Perhaps one of the most potent natural alternatives for diabetes, berberine is a standout natural supplement with studies to back it.

Berberine is a compound found in some plants and is most often used as a natural alternative for treating insulin resistance and high blood sugar.

According to a small study on people with metabolic syndrome (a condition that can lead to type 2 diabetes), berberine improved insulin sensitivity and reduced the waist circumference of participants (8). 

Berberine might even be as effective as some prescription medications. A pilot study compared berberine vs metformin (a popular first-line medication for diabetes) for their ability to help treat symptoms of type 2 diabetes (9). 

The researchers found that berberine produced identical results as metformin in terms of improving blood glucose metabolism. 

Berberine may also help promote weight loss, similar to Rybelsus and Trulicity.

Conclusion

Rybelsus and Trulicity are both types of GLP-1 receptor agonists, which help increase insulin secretion and can cause weight loss by reducing appetite and slowing stomach emptying.

Their main difference is that Rybelsus is an oral medication for daily use, while Trulicity is a once-weekly injectable. 

Both medications carry similar side effects and risks and appear equally efficient at lowering blood sugar levels and promoting weight loss, according to the studies referenced in this article.

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