Semaglutide tablets vs. injection: Which is best?

In this article:

• Comparing efficacy
• Comparing side effects
• Comparing cost
• The bottom line

In this article

• Comparing efficacy
• Comparing side effects
• Comparing cost
• The bottom line

Semaglutide drugs have become practically ingrained in the fabric of our culture. They’ve been in the news, documentaries, commercials, and even the lyrical barbs of rap beefs. Their popularity is in part because they work so well. GLP-1 receptor agonists mimic the glucagon-like peptide-1 hormone to increase insulin secretion and slow digestion, helping manage blood sugar levels and decrease body weight.

The wave of semaglutide medications on the market comes as brand-name injectable versions like Ozempic and Wegovy or oral medications like Rybelsus. These two different forms are similar in most ways, including their mechanism of action, tolerability, and side effects, but there are still some important differences to note.

Are semaglutide tablets as effective as injections?

Tablets might be enticing to anyone who shudders at the sight of needles, but do they work as well? Oral formulations have proven effective for both lowering blood glucose and weight loss. However, despite very little head-to-head data comparing oral and injectable semaglutide, some evidence suggests injectable forms might be slightly more effective.

For example, a 2021 report published in Frontiers in Endocrinology showed that over 30–56 weeks, injectable semaglutide reduced A1C numbers by 1.5–1.8%, while semaglutide tablets reduced them by 1.0–1.4%. A 2024 study in Diabetes Obesity Metabolism, however, showed similar A1C decreases for injectable and oral forms.

The story is pretty much the same for weight loss—both work well, but there’s a chance that injectable semaglutide is slightly better. An observational study from Croatia, published in Diabetology, found that the same proportion of injectable and oral semaglutide patients achieved ≥5% weight loss. In comparison, slightly more injectable formulation patients achieved ≥10% weight loss than those who took tablets. The above study from Diabetes Obesity Metabolism said: “The average change in body weight was similar in the two groups (-3.7 kg with injectable and -3.3 kg with oral at 18 months), but more new users of injectable semaglutide lost ≥5% body weight.”

According to Dr. Michael Chichak, MD, medical director of MEDvidi, “This is due to the increased bioavailability achieved by subcutaneous injections, which allows for a more consistent dose. However, the tablets provide convenience and appeal to patients who are afraid of needles.”

That said, there’s a much larger difference for anyone with cardiovascular issues. “Ozempic has data to support cardiovascular risk reduction, while Rybelsus does not,” says Dr. Diana Roman, Pharm.D., clinical pharmacist and assistant professor at Marshall B. Ketchum University. “In patients with diabetes and cardiovascular disease or high risk for cardiovascular disease, Ozempic would be preferred over Rybelsus from a cardiovascular risk reduction perspective. However, if a patient prefers an oral option, Rybelsus is still a good choice for glycemic control and weight management.”

Semaglutide tablets vs. injections: Side effects

Tablets and subcutaneous drugs circulate the body differently—tablets are absorbed through the digestive system, while injections go straight into the bloodstream. Going through the digestive system metabolizes tablets and causes the medication to have less bioavailability, so oral doses typically are higher than injections. The standard dose of oral semaglutide is 7–14 mg once per day, while an injectable GLP-1 like Ozempic only requires a 0.5–2 mg dose once per week.

The possibility of side effects is a given for most drugs, and these are no exception. Clinical trials for Rybelsus and Ozempic have shown that the most common side effects for both formulations are gastrointestinal, like nausea, vomiting, diarrhea, abdominal pain, and constipation. “These usually appear early in the course of treatment and gradually go away as the body adapts,” Dr. Chichak says, which is why doctors typically increase the dosage gradually.

Injections may also cause reactions at the injection site, so patients are typically advised to rotate where they administer it. However, per Dr. Alatassi, “oral semaglutide is associated with higher rates of gastrointestinal side effects such as nausea, vomiting, and diarrhea compared to the injectable form. These symptoms are often dose-dependent and more common during the titration phase.”

The serious side effects are similar, too. In rare cases, both formulations can cause pancreas inflammation (pancreatitis), gallstones, low blood sugar (hypoglycemia), increased heart rate, and complications with diabetic retinopathy—an eye issue that stems from diabetes.

For patients who decided they’d rather forgo needles, it’s possible to switch from injectable forms to once-daily oral semaglutide. “This requires careful consideration of dosing equivalency, adherence, and therapeutic goals,” Dr. Alatassi says. “A healthcare provider should supervise this transition to ensure safety and efficacy.” The change might also come with some changes to blood sugar levels—one study found that patients’ blood sugar increased by an average of 9 mg/dL after going from once-weekly 0.5 mg injectable semaglutide to daily 7 mg oral semaglutide.

Cost of semaglutide tablets vs. injections

For people who have no preference between tablets and subcutaneous injections, the decision might come down to price. Unfortunately, for semaglutide, the average costs are pretty even. Rybelsus often costs $1,353 per 30-day supply, while Ozempic costs $1,345.

Those prices might seem intimidating, but there are a few reliable ways to save on either drug. For example, SingleCare coupons can decrease Rybelsus’s price to $858 and Ozempic’s price to $811. Signing up for SingleCare is free, and then it’s just a matter of presenting the card at a participating pharmacy to reap the savings.

Additionally, both drugs are often covered by insurance, Medicare, and Medicaid when they’re medically necessary and prescribed for Type 2 diabetes. Since neither drug is FDA-approved for weight loss, they’re not typically covered. However, Wegovy is another injectable semaglutide drug that’s approved for weight management, which means some plans might cover it. Regardless of which drug you get or what condition it’s treating, insurance coverage depends entirely on your specific plan’s policies, so check your insurance’s formulary to know for sure.

The bottom line

Whether it’s because they work better with your lifestyle, your insurance plan prefers them, you get injection site reactions, or simply because needles make you squirm, there are plenty of valid reasons to choose semaglutide tablets. Even though some research suggests that weekly injections might work marginally better, oral versions are still effective for Type 2 diabetes treatment and work off-label for weight reduction as well. Yet choosing a GLP-1 medication isn’t a decision to make on a whim. Always consult a healthcare provider first—they know your chronic medical conditions, wellness, and other meds better than anyone else and have the expertise to develop an individualized treatment plan.