Guide to oral GLP-1 medications for weight loss and diabetes

For many years, there has only been one oral GLP-1 available: Rybelsus. But that changed with the approval and launch of the Wegovy pill in December 2025. Below, we review the current landscape of oral GLP-1 drugs, how they work, and how they compare to their injectable counterparts.

Oral GLP-1s are oral medications that work by mimicking glucagon-like peptide-1 (GLP-1), a gut hormone involved in appetite and blood sugar regulation. Currently, the US Food and Drug Administration (FDA) has only approved two oral GLP-1s:

• Rybelsus, which contains the same active ingredient as injectable Wegovy and Ozempic (semaglutide) and is approved for type 2 diabetes. 

• Wegovy pill, which is a higher-strength version of semaglutide than what’s found in Rybelsus. It’s approved for weight loss and cardiovascular risk reduction in adults with obesity or overweight.

There may be another oral GLP-1 to add to that list soon. Eli Lilly is currently seeking FDA approval for orforglipron. If approved, orforglipron would likely be prescribed for weight loss and type 2 diabetes.

Oral GLP-1 drugs work for weight loss by reducing appetite, increasing feelings of fullness, and slowing down digestion (so you physically feel full sooner and longer). For blood sugar control, they work by increasing the release of insulin and reducing glucagon after you eat.

*Note: information about orforglipron is based on clinical trials because it has not yet been approved by the FDA.

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Rybelsus

The active ingredient in Rybelsus is semaglutide, the same as Wegovy and Ozempic. When used with diet and exercise, it is FDA-approved to:

• Control blood sugar levels in adults with type 2 diabetes

• Reduce cardiovascular risk in adults with type 2 diabetes

Rybelsus follows a dosage titration schedule. You typically start at a low dosage of semaglutide and gradually increase your dosage over a period of 30–60 days. It comes in two dosage formulations:

• Formulation R1: 3 mg, 7 mg, 14 mg

• Formulation R2: 1.5 mg, 4 mg, 9 mg

Your healthcare provider will prescribe one of these formulations for you. 

• If you’re prescribed Formulation R1, you’ll likely start at a 3 mg dosage daily. After 30 days, you’ll increase to 7 mg. If you need more blood sugar control after 60 days, your provider will have you increase to 14 mg. 

• Formulation R2 follows a similar schedule.

Rybelsus is taken daily in the morning by mouth, at least 30 minutes before any food, water, and other medications. 

Rybelsus has a list price of $997.58 for a 30-day supply. But if you have health insurance, you’ll pay much less — as low as $10 per month if you’re eligible for the manufacturer savings offer. 

Wegovy pill  

The Wegovy pill is made by Novo Nordisk, the same manufacturer behind injectable Wegovy and Ozempic, as well as oral Rybelsus. Its active ingredient is semaglutide. The Wegovy pill is FDA-approved for:

• Weight loss in adults with obesity or overweight with at least one weight-related health condition (such as type 2 diabetes or obstructive sleep apnea)

• Cardiovascular risk reduction in adults with heart disease and obesity or overweight

Like Rybelsus, Wegovy follows a dosage titration schedule. You generally start at a low dose of 1.5 mg and gradually increase your dosage to 25 mg over a period of 30–90 days.

The Wegovy pill is taken daily in the morning by mouth, at least 30 minutes before any food, water, and other medications. It should be used in combination with lifestyle changes like diet and exercise.

Depending on the dose, the Wegovy pill costs $149–$299 per month through Ro. It also has a list price of $1,349.02.

Orforglipron

Orforglipron is made by Eli Lilly, the same manufacturer behind the injectable GLP-1 medications Mounjaro and Zepbound. Orforglipron is the active ingredient. 

We don’t know yet what the brand name will be. Eli Lilly plans to seek FDA approval for orforglipron for:

• Weight loss in adults with obesity or overweight with at least one weight-related health condition (such as type 2 diabetes or obstructive sleep apnea) 

• Type 2 diabetes in adults

Orforglipron has been studied in several dosage strengths: 3 mg, 12 mg, 24 mg, 36 mg, and 45 mg. We don’t yet know what the approved dosage titration schedule will be. 

In clinical trials orforglipron was taken daily in the morning by mouth, with or without food. It should be used in combination with lifestyle changes like diet and exercise. 

As of publication, the list price of orforglipron is still TBD. According to Lilly, however, the medication will be available starting at $149 for self-pay patients if (and, hopefully, when) it’s FDA-approved. From there, additional doses of orforglipron can cost up to $399. 

Oral GLP-1s can produce an average weight loss of 6%–15%, depending on the medication:

• Rybelsus (semaglutide) produces nearly 6% weight loss in one year, according to a small study of adults with obesity. But it isn’t even approved for weight loss — it’s approved for type 2 diabetes — so taking Rybelsus for weight loss is considered an off-label prescription.

• The Wegovy pill (25 mg) produces an average weight loss of 13.6% in 64 weeks (about a year and three months), according to a study of adults with obesity or overweight. In higher doses of 50 mg (which may be prescribed off-label), the average weight loss is 15.1% in 68 weeks, according to a separate study. 

• Orforglipron can produce an average weight loss of 8.6%–12.6% in just six months, according to clinical trials. At nine months, the weight loss ranges from 9.4%–14.7%.

Oral GLP-1s are effective at blood sugar control. Here’s what the research shows:

• Rybelsus (14 mg) reduced HbA1c levels by an average of 1.4% in six months in clinical trials.

• Orforglipron (36 mg) reduced HbA1c levels by an average of 1.5% in 40 weeks (10 months) in clinical trials. 

• The Wegovy pill reduced blood sugar levels to a normal level for 71% of people with prediabetes, compared to only 33% of people taking a placebo. While the Wegovy pill has not been studied in people with type 2 diabetes, it may help lower blood sugar levels, according to an analysis of the OASIS 4 clinical trial.

Oral GLP-1s have similar side effects to injectable GLP-1s, with the most common ones being gastrointestinal in nature. These include:

• Nausea

• Abdominal pain

• Diarrhea

• Vomiting

• Constipation 

These side effects are most frequent when starting the medication and when increasing the dose.

Since it’s not yet FDA approved, we don’t have a full risk profile of orforglipron. 

However, for reference, the most common risks of oral GLP-1s like Rybelsus and the Wegovy pill include:

• Acute pancreatitis

• Diabetic retinopathy complications (diabetes-related vision changes)

• Hypoglycemia (low blood sugar), especially when used with insulin

• Kidney or gallbladder issues

• Severe gastrointestinal reactions

• Allergic reactions

• Pulmonary aspiration during general anesthesia or deep sedation

Rybelsus and Wegovy also carry a black box warning for thyroid tumors based on animal studies. While it’s unknown if semaglutide has the same effect in humans, anyone with a personal or family history of thyroid cancer should not take oral or injectable semaglutide.

Oral GLP-1s are available in different dosage strengths. 

Both Rybelsus and Wegovy follow a dosage titration schedule, where you start at the lowest dose and increase every 30 days until you reach an effective maintenance dose. 

Orforglipron does not yet have an official dose or dosage schedule yet. But it was taken once daily with a dosage titration schedule (like Rybelsus and the Wegovy pill) in clinical trials.

*Note: information about orforglipron is based on clinical trials because it has not yet been approved by the FDA.

Generally, oral GLP-1s should be taken in the morning. 

• Rybelsus and the Wegovy pill should be taken on an empty stomach, at least 30 minutes before any food, water, or other medications. 

• Orforglipron can be taken with or without food, according to clinical trials.

The cost of oral GLP-1s varies depending on the medication prescribed, insurance coverage (if any), and other factors. 

• Rybelsus has a list price of $997.58 per month, but the exact amount paid is often much lower with health insurance. Plus, some people may qualify for the manufacturer savings offer, which can bring the cost to as little as $10 per month. 

• The Wegovy pill has a list price of $1,349.02 or cash price of $149–$299, depending on dose. With commercial health insurance coverage, the Wegovy pill can cost as little as $25 per month. 

• Orforglipron will have a cash price of $149 for the lowest dose if and when it’s FDA approved, according to Lilly. From there, the price can go up to $399. 

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Here’s what to remember if you’re considering an oral GLP-1 for diabetes or weight loss.

• Rybelsus was the first FDA-approved oral GLP-1 and is approved for type 2 diabetes.

• The Wegovy pill is the first oral GLP-1 that’s approved for weight loss. 

• Orforglipron is not yet approved for either type 2 diabetes or weight loss.

• Oral GLP-1s work similarly to injectables by reducing appetite, slowing down digestion, and improving blood sugar control.

• Weight loss results vary by drug, with Rybelsus producing more modest losses (~6% in a year) and Wegovy and orforglipron producing results on par with injections (~13%–15% in a year).

• Cost and insurance coverage differ widely, so the “best” oral GLP-1 depends on your health goals, tolerance for side effects, and budget.