Wegovy Shots vs. Wegovy Pills for Weight Loss and Heart Protection

Semaglutide has gotten a lot of attention over the past few years. If you don’t recognize this generic drug name, you probably do recognize the brand names: Ozempic for type 2 diabetes and Wegovy for weight loss. Both these GLP-1 agonist medications are self-administered injections, but not everyone is enthusiastic about needles. The FDA has just approved Wegovy pills for weight loss. The highest dose will be 25 mg, which is quite a bit higher than the dose for the injections. A study in the New England Journal of Medicine (Sept. 18, 2025) demonstrated success for this formulation. The average weight loss for those study participants was about 14% of their initial weight in the course of more than a year. So here’s the question: Wegovy shots or Wegovy pills for weight loss? It’s a lot more complicated than you might imagine.

How Well Did Oral Semaglutide Work for Weight Loss?

First, a little surprise. An oral form of semaglutide has been available for over six years. It’s called Rybelsus and the FDA approved a variety of doses: Rybelsus R1 formulation comes in 3 mg, 7 mg and 14 mg pills. Then there’s Rybelsus R2 formulation that comes in 1.5 mg, 4 mg and 9 mg pills. These oral formulations are approved for glucose control in the treatment of type 2 diabetes. The maximum daily dose = 14 mg of semaglutide.

A Reader Reports on Rybelsus:

Q. I started taking Rybelsus early last year to help control type 2 diabetes. In addition to blood sugar control, this pill helped me lose 50 pounds.

I know Rybelsus is the same medicine as Ozempic and Wegovy. Ozempic can cause gastroparesis. Can Rybelsus also cause this?

A. Gastroparesis means stomach paralysis. The drug semaglutide (Ozempic, Rybelsus, Wegovy) can cause delayed stomach emptying. Symptoms may include abdominal discomfort, a sense of fullness or bloating, nausea, vomiting or indigestion.

Rybelsus has not been FDA approved for weight loss, even though it contains the same active ingredient, semaglutide, that is found in Wegovy shots. But a study in the New England Journal of Medicine (Sept. 18, 2025) reveals that oral semaglutide can also help people lose weight. About one third of the participants taking the drug lost about 20 percent of their body weight.

The Novo Nordisk drug company is reported to have applied to the FDA for approval to market an oral form of semaglutide for weight loss. It may be called Wegovy, like the injectable form of this medicine.

Semaglutide Against Heart Disease:

A new study published in the Lancet (Oct. 22, 2025) suggests that when researchers treat diabetes with the injectable GLP-1 agonist semaglutide that it can protect the heart. Researchers call serious heart and vascular problems MACE (major adverse cardiovascular events). This designation stands for heart attacks, strokes and/or death from vascular or cardiac causes. In other words, MACE is not something you want to encounter!

Previous research has found benefit with the use of injectable semaglutide sold under the brand names Ozempic and Wegovy. The new analysis demonstrates that the same semaglutide, also prevents cardiovascular complications.

A subanalysis of the SELECT trial found that the benefits of semaglutide do not depend upon weight loss. Even people who did not lose significant weight had lower risks of heart attacks and strokes. A decrease in waist size, however, was associated with the protective cardiovascular effect.

Here is how the researchers describe the benefits of semaglutide:

“These findings suggest that the cardioprotective effects of semaglutide extend beyond its impact on adiposity, with important implications for clinical practice and understanding of the mechanisms responsible for the benefits from GLP1-RAs.”

The bottom line seems to be that semaglutide can protect the heart from MACE. That’s even if it does not lead to a substantial amount of weight loss. The authors suggest that semaglutide could help the heart even if patients do not need to lose weight.

The New England Journal of Medicine Research:

As mentioned above, a study of oral semaglutide (25 mg) was published in the New England Journal of Medicine (Sept. 18, 2025). At the start of the study 205 participants were randomly assigned to get semaglutide and 102 participants were randomly assigned to get placebo pills. At the end of the trial, the people in the oral semaglutide group did significantly better than those on placebo:

RESULTS:

“In the oral semaglutide group, 152 of 192 of the participants with an observation at week 64 (79.2%) had a reduction in body weight of 5% or more, 121 (63.0%) had a reduction of 10% or more, 96 (50.0%) had a reduction of 15% or more, and 57 (29.7%) had a reduction of 20% or more; in the placebo group, 28 of 90 of the participants (31.1%) had a reduction of 5% or more, 13 (14.4%) had a reduction of 10% or more, 5 (5.6%) had a reduction of 15% or more, and 3 (3.3%) had a reduction of 20% or more.”

Here is how the authors describe the potential benefits of oral semaglutide (Wegovy Pills):

“Currently available GLP-1 receptor agonists for the treatment of obesity are administered subcutaneously; oral formulations that do not compromise efficacy would offer patients greater choice. The reasons patients may prefer oral administration over the subcutaneous route are most often needle aversion and local skin reactions. In addition, unlike injectable agents, oral agents may not require a refrigerated chain of delivery and could widen the reach of obesity care in many regions of the world where a lack of refrigeration represents a barrier to access.”

The Bottom Line on Wegovy Pills:

Not surprisingly, oral semaglutide performed better than placebo. Almost one third of the people taking Wegovy pills lost at least 20% of their body weight. That’s not shabby. Nonetheless, the new Wegovy pills may be challenging for some people to take. That’s because they must be swallowed on an empty stomach. Patients will need wait at least 30 minutes before eating or drinking anything other than the water used to swallow the pill. Some people, perhaps many, will discover they prefer the weekly shot to daily pills.

What About the Side Effects of Wegovy Pills?

If we look at the side effects associated with oral Rybelsus at a dose of 14 mg we see that the active drug caused:

• Nausea in about 20% of patients
• Abdominal pain in about 11% of patients
• Diarrhea in about 10% of patients
• Decreased appetite in about 9% of patients
• Vomiting in about 8% of patients
• Constipation in about 5% of patients

In the oral semaglutide study published in the New England Journal of Medicine, the side effects reported at the 25 mg dose were:

• Nausea in about 47% of patients
• Vomiting in about 31% of patients
• Nasal symptoms in about 21% of patients
• Constipation in about 20% of patients
• Indigestion in about 18% of patients
• Diarrhea in about 18% of patients
• Headache in about 12% of patients
• Burping in about 10% of patients

Another Downside of Wegovy Pills:

You might think that people would much prefer oral medicine to an injection. A diabetes expert we consulted challenged that idea.

He pointed out that oral semaglutide (Rybelsus) for diabetes has these important instructions:

• “Take RYBELSUS on an empty stomach in the morning with water (up to 4 ounces of water). Do not take RYBELSUS with other liquids besides water.
• After taking RYBELSUS, wait at least 30 minutes before eating food, drinking beverages or taking other oral medications.
• Swallow tablets whole. Do not split crush or chew.”

A lot of people hit the ground running in the morning…metaphorically, that is. They may not have time to wait 30 minutes before having a cup of coffee or tea and eating breakfast. Instead of self-injecting semaglutide once a week, people have to take a pill every day. That’s one more thing to remember. And it will slow some folks down.

Microdosing Semaglutide vs. a Wegovy Pill:

I am not going to go into much detail on microdosing semaglutide shots. This is not FDA-approved! It is considered experimental and unproven. But we have been hearing through the grapevine that some people are injecting smaller doses of semaglutide to reduce the risk of side effects.

Some doctors are supervising this strategy to “personalize” the dose. The goal is to maintain effectiveness and reduce the likelihood of adverse reactions. It clearly needs thorough testing, something the drug company may not want to do.

Final Words:

Now that the FDA has approved Wegovy pills, please let friends and family know that if they have been trying to lose weight for a long time and if they hate shots, oral semaglutide just might be an option.