Do semaglutide tablets work?

In this article:

• Semaglutide tablets
• Efficacy
• Alternatives
• The bottom line

In this article

• Semaglutide tablets
• Efficacy
• Alternatives
• The bottom line

In a 2024 KFF survey, one out of every eight Americans said they had taken a GLP-1 drug like semaglutide. These are some of the hottest medications for Type 2 diabetes and weight loss in the country, helping millions manage their high blood sugar and weight. Semaglutide imitates a hormone called glucagon-like peptide-1, which stimulates insulin production. It also delays gastric emptying, tempering the appetite.

Semaglutide is most often administered as an injection, but it is also available as a tablet. However, there are some things to consider before starting treatment.

Does semaglutide come in tablet form?

Yes, even though semaglutide was originally introduced as a subcutaneous injection (Ozempic, Wegovy), an oral version hit the market just a couple of years later. Drug manufacturer Novo Nordisk produces it under the brand name Rybelsus, and the FDA approved it for managing blood glucose in people with Type 2 diabetes but not Type 1 diabetes. Some healthcare providers might prescribe it off-label for weight management as well.

Currently, there’s no generic version of oral semaglutide, and according to the FDA, Rybelsus is patent-protected until 2034, so there likely won’t be one until then. Some compounding pharmacies might make semaglutide tablets themselves, but these drugs aren’t FDA-approved or inspected.

Aside from how you take Rybelsus or Ozempic, the dosage forms and dosing schedule are the main differences. The standard dosage for Rybelsus is 7–14 mg, once daily, while an injection like Ozempic only requires a 0.5–2 mg dose once weekly. The higher dose of Rybelsus is because oral drugs take longer to enter the bloodstream, giving them lower bioavailability. Otherwise, oral and injectable semaglutide drugs have similar side effects, interactions, warnings, and costs.

What are the side effects?

The common side effects of semaglutide include nausea, diarrhea, vomiting, abdominal pain, constipation, and headache. Serious possible side effects include pancreas inflammation (pancreatitis), low blood sugar (hypoglycemia), gallbladder issues, thyroid tumors, fast heartbeat, kidney problems, and allergic reactions.

“Gastrointestinal side effects such as nausea and vomiting are more frequently reported with oral semaglutide,” says Dr. Diala Alatassi, MD, obesity medicine specialist at Endeavor Health. “In my experience, many patients tolerate these symptoms better with gradual dose escalation and by taking the medication as directed—on an empty stomach with water and waiting 30 minutes before eating or drinking anything else.”

Efficacy of semaglutide tablets

The big question is: Does it work? “Yes, due to its glycemic and weight loss effects, oral semaglutide (Rybelsus) is a great option for patients with Type 2 diabetes who would also benefit from weight loss,” says Dr. Diana Roman, Pharm.D., clinical pharmacist and assistant professor at Marshall B. Ketchum University. “Rybelsus belongs to the class of agents, GLP1RAs, which are effective agents for glycemic control and weight loss.”

Dr. Michael Chichak, MD, medical director of MEDvidi, agrees. “Semaglutide tablets are especially beneficial for people who are afraid of injectable drugs but still want strong blood sugar control. In conjunction with lifestyle changes, they are a great way to lower fasting and postprandial glucose levels,” he says.

Additionally, a 2024 study in Diabetes Epidemiology and Management found that oral semaglutide reduced hemoglobin A1C by an average of 3.1%. Clinical trials had similar (albeit slightly less significant) results, showing an A1C reduction of 1.0–1.4%. Either way, it has proven effective in lowering blood sugar for people with Type 2 diabetes.

Even though it’s technically an off-label treatment, oral semaglutide is just as effective for weight loss. A 2022 study in Nature Medicine found a mean body weight reduction of 15.2% over 104 weeks, compared to 2.6% for the placebo group. Likewise, the study from Diabetes Epidemiology and Management saw a mean reduction in body mass index (BMI) of 13% at six months and 19.7% at 12 months.

There haven’t been any studies directly comparing the efficacy of oral and injectable semaglutide. Both have shown to be safe and effective in separate trials, but some research suggests that injectable versions might be marginally more effective for A1C reduction and weight loss.

However, per Dr. Roman, there’s a difference in their cardiovascular effects. “While Ozempic has data to support its cardiovascular risk reduction, Rybelsus does not,” she says. So, injectable semaglutide like Ozempic might be a better option for people who have diabetes and a high risk for cardiovascular disease.

Alternatives to semaglutide tablets

The high demand for semaglutide and its fluctuations in supply has left many people looking for substitutes. There are a few good options, but there are also a few unauthorized ones you should avoid.

Other diabetes medications

“Drugs like SGLT-2 inhibitors, like empagliflozin, or other GLP-1 agonists, like dulaglutide, may be appropriate choices for blood sugar regulation,” Dr. Chichak says. “Newer drugs, such as tirzepatide, a dual GLP-1, and GIP receptor agonist, are quickly gaining traction and demonstrating encouraging outcomes in clinical trials for weight management.”

Other popular diabetes medications include metformin, gliflozins (Farxiga, Jardiance), and sulfonylureas (Glucotrol, Amaryl). 

What about compounded semaglutide?

Compounding pharmacies create medications—including semaglutide—from scratch, sometimes custom-mixing drugs tailored to the patient’s needs. These pharmacies are subject to regulation by state boards but not by FDA approvals. The FDA has expressed concerns about compounded semaglutide, primarily because of reports about patients accidentally taking too much.

Avoid online sources

The FDA also warns against purchasing semaglutide products online after discovering counterfeit versions being marketed illegally. These counterfeit drugs, they said, could contain too little semaglutide, the wrong ingredients, or no active ingredient at all, rendering them ineffective and unsafe.

“Patients must avoid over-the-counter products claiming to contain semaglutide or similar compounds,” Dr. Alatassi says. “These unapproved products often lack quality control and pose significant health risks. Semaglutide should only be prescribed by a healthcare professional and dispensed by a licensed pharmacy.”

OTC weight loss supplements

There are also a range of other over-the-counter weight loss supplements. Americans spend around $2 billion on them per year, but do they work? The only OTC weight loss pill approved by the FDA is Alli (orlistat), and studies have shown that it’s effective for obese patients as an adjunct to therapeutic lifestyle changes. However, a study in Obesity cited a lack of evidence for the effectiveness of other OTC supplements. Plus, Poison Control warns against taking these supplements, and even though the FDA doesn’t regulate them, they keep a list of ones that could be tainted or harmful.

The bottom line

Semaglutide tablets are typically a viable oral medication for most people with diabetes or obesity. Research has proven them effective for both conditions, and they’re a great alternative to injectable options like Ozempic or Wegovy. That said, it’s best to get medical advice from a healthcare provider before choosing an antidiabetic or weight management drug. They know your health and circumstances, and they’ll develop a treatment plan that’s safe and effective for your particular condition.