Rybelsus vs Ozempic: Could a New Pill Version of the Weight Loss Drug Beat Out the Injectable? Two Doctors Weigh In

Ever since being granted approval by the FDA, the prescription injectable medication known as Ozempic has been on the lips of anyone looking for help to manage their type 2 diabetes and folks looking to lose weight with deep pockets who aren’t put off by injecting a drug. Given the popularity of this weight-loss shot, many are surprised to learn that Ozempic’s active ingredient — semaglutide — is now available in a pill form under the brand name Rybelsus. In the match-up of Rybelsus vs Ozempic, we wonder are the pills as good as the shots? We ask two doctors to weigh in.

How does semaglutide work in the body?

For starters, it’s important to understand how the active ingredient semaglutide works, no matter if it’s injected or taken orally as a pill. Semaglutide is known by scientists as a GLP-1–stimulating drug because it functions as the glucagon-like peptides — also known as hormones — that occur naturally in the gut.

These glucagon-like peptides reduce appetite and delay stomach emptying so people feel full longer. And if you feel full longer, you necessarily feel less hunger. Less hunger, in turn, results in reduced calorie intake — and improved weight loss and blood-sugar regulation, as reported by The New England Journal of Medicine.

Many experts see exogenous (taken via injection or pill) semaglutide as a way to level the weight-loss playing field. “People with the disease of obesity actually can have lower levels of GLP-1 than those who are thin,” explains Shauna Levy, MD, medical director of Tulane Hospital’s Bariatric and Weight Loss Center. Dr. Levy has seen semaglutide medications help her patients.

The thinking is that by adding semaglutide to the system through external means (i.e., via injection or pill), the bodies of overweight people will work more like the bodies of naturally slim folks who already produce plenty of the hormone on their own. (Click through to our sister publication to see natural ways to raise your GLP-1 levels.)

How do weekly Ozempic shots work?

Ozempic shots are routinely available by prescription in three dosages — 0.5mg, 1mg and 2mg. In each case, the dose is injected using a single-use injection pen. The shots need to be injected directly into body fat — most often in the belly or hip region. This allows for rapid absorption of the medication into the bloodstream. These shots are to be used once weekly, with experts recommending they be administered around the same time and day each week.

One of the complaints about Ozempic is that the medicine’s potency tends to fade toward the end of its 7-day cycle. “I have patients report that they feel more hungry on day six than, you know, day two or three,” explains Dr. Levy. “I think it’s probably more effective on a six-day dosing. But that’s complicated.”

As a work-around, certified master nutritionist Christina Jordan recommends “giving the shot on Wednesday or Thursday so you’re peaking on the weekend, if that’s the time where you tend to have occasion to eat more.” Jordan runs a bariatric nutrition clinic called Fit Body Weight Loss in Arizona where a doctor prescribes semaglutide shots. Jordan herself has lost 38 pounds with the shots. She says, “As a holistic nutritionist, I literally can’t recommend the shots enough.”

How do daily Rybelsus pills work?

If you wince at the thought of jabbing yourself with a needle, you’ll be relieved to learn about the new oral pill option. Rybelsus is currently the only way to get semaglutide in a tablet form. Researchers of one study reported, “Oral semaglutide may be an attractive option for patients with type 2 diabetes who require improved glycemic control, would like to lose weight and who are not interested in injectable therapy.”

Rybelsus works in the same way as Ozempic. It increases the amount of insulin that is released from the pancreas and slows food leaving the stomach after eating to suppress appetite and speed weight loss.

The Rybelsus pill should be taken by mouth on an empty stomach as soon as you wake up in the morning with a sip — less than 4 oz. — of water, according to the manufacturer. Then simply wait 30 minutes before eating or drinking for best results.

What is the Rybelsus dosage for weight loss?

In comparison to the weekly shot of Ozempic, Rybelsus is taken once a day in either a 7mg or 14mg dose. The Rybelsus dose is much higher than the Ozempic dose, since the human gut is only able to absorb a fraction of the active ingredient during the digestion process. Poor absorption is a common problem with all sorts or oral medicines and dietary supplements, including vitamin D. And scientists have taken that into account when dosing the Rybelsus pill.   

Is Rybelsus as effective as Ozempic?

Rybelsus appears to be similarly effective as Ozempic at certain doses. The higher-dose pill (14mg) was shown to reduce A1C levels (a measure of how your body regulates blood sugar levels over a 3-month period) by 1.3% in 6 months, and is linked to losing 10 pounds in a year, according to research published in the journal Diabetes Care. By comparison, the Lancet journal reported that low-dose Ozempic shots (0.5mg) helped subjects reduce A1C by 1.3% and shed 9.5 pounds.

The balance tips in favor of the shots when using higher doses of the shots — at the higher dose (1mg), the shots handily outperform the pills. Weight-loss results increase as the dosage increases, but so do chances of digestive upset and other side effects.

Although the pill may appeal to those with a needle aversion, physician nutrition specialist Melina Jampolis, MD, cofounder and chief medical officer of Ahara and author of Spice Up, Slim Down, says more of her patients still use the shots than the pills. She explains, “Most patients don’t ask for it even though it is oral. They find a weekly medication is easier.” One upside to the pill: It’s more portable and doesn’t need to be stored in the fridge.

Compliance is an important factor when it comes to healthcare measures. Most experts agree the best medication is one a patient will actually remember to take. That may be why Dr. Jampolis says, “I have not found that the pill works as well in patients, sadly.”

Other differences between Rybelsus and Ozempic

Both the Ozempic shot and Rybelsus pill contain the same active ingredient, just with different ways of getting it into the body. And both the shot and pill are manufactured by the same pharmaceutical company, Novo Nordisk. For best results, both options should be paired with healthy diet and exercise efforts.

The two options also run about the same price, with Dr. Jampolis adding, “The pill is not cheaper.” And, as many patients have discovered, the prices can be steep: on average $1,200 for a 1-month supply. This cost is often covered by insurance when prescribed as a diabetes treatment, but it is not covered when prescribed for weight loss.

What are the side effects of Rybelsus?

“Safety is the same between the shot and the pill since it’s the same drug,” says Dr. Jampolis. Both the pills and shots are associated with temporary side effects, including about 20% of users experiencing nausea and around 9% to 10% experiencing diarrhea, according to the FDA.

That’s something Dr. Levy has seen in her practice, noting, “In my experience patients have more nausea with Rybelsus.” In addition, users are at risk for possible, rare, serious side effects including thyroid tumors, cancers, pancreatitis or problems with the gallbladder and kidney. Adds Dr. Levy, “Rybelsus appears to be safe although there was a finding of increase benign skin tumors, which we will need to keep studying.”

One side effect of both semaglutide shots and pills that has garnered headlines is loss of facial or “buccal” fat. “As people begin to lose weight, they often lose fatty deposits in their face. This results in rapid facial aging that has become so common, plastic surgeons have nicknamed it ‘Ozempic Face,’ as women come flocking for fillers and face lifts,” explains Georgia-based family medicine doctor Ellie Campbell, DO. 

Compared to risky diet drugs of past generations, however, Dr. Levy adds, “These are the best weight-loss medications on the market, hands down, because they have the lowest side effect profile and they actually work.”

How to save on Rybelsus

A one-month supply of Rybelsus runs around $1,200 to $1,400, which is similar to Ozempic. If you have diabetes and are prescribed Rybelsus, that price is almost always covered by insurance. But if you’re prescribed the shot for weight loss, it is not covered about 80% of the time. “There’s a weight stigma with pricing,” says Dr. Levy. “Instead of approving these shots as a preventive tool, insurance policies block patients from getting treatment until they develop diabetes.”

And yet there are ways to keep costs to a minimum, even if you don’t have diabetes: The manufacturer of Rybelsus offers a helpful website that will take you through a process that helps you find the most savings that you’re eligible for.

The future of Rybelsus and Ozempic

The drug manufacturer continues to test higher doses of the oral tablet and is awaiting approval from the FDA. Patients can currently get a higher dose (2.4mg) semaglutide injection under the brand name Wegovy. Time will tell if the pills catch on as much as Ozempic or Wegovy shots. One thing is clear, as Dr. Levy points out, “This is merely the beginning. There are 25 other drugs in the works for weight loss, so we’re just scratching the surface. This is very exciting because it gives us more options to treat patients with obesity.”

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For more on the side-effects Ozempic can have on your face, click through to view Sharon Osbourne’s amazing weight loss transformation with Ozempic.)

This content is not a substitute for professional medical advice or diagnosis. Always consult your physician before pursuing any treatment plan.