GLP-1 pill: Is a GLP-1 pill a good alternative to injectable GLP-1 meds?

It’s absolutely no surprise that glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) are big news right now. Medications from the glucagon-like peptide 1 receptor agonist drug class, like Ozempic® (semaglutide) and Saxenda® (liraglutide), have made national headlines because of shortages, undeniable weight loss success, and their cost.

Indeed, popular GLP-1s are approved by the U.S. Food and Drug Administration to be prescribed for type 2 diabetes or overweight and obesity. GLP-1s work by mimicking the GLP-1 incretin hormone your body already makes that lowers blood sugar and controls appetite. This makes them extremely helpful in managing blood glucose levels in those being treated for type 2 diabetes, and the appetite mechanism aids in weight loss.

Even more, some GLP-1s like Trulicity® (dulaglutide) even help lower your risk of adverse cardiovascular events like heart attack and stroke. Additionally, the GLP-1 obesity drug Wegovy® slows digestion, also known as gastric emptying, making you feel fuller longer and promoting weight loss.

On top of that, Mounjaro® (tirzepatide)—a novel GIP/GLP-1 med—has gone leaps and bounds above other weight loss drugs, with some patients seeing up to a 22.5 percent body weight loss during a clinical trial conducted by manufacturer Eli Lilly. It’s a cousin to the  GLP-1 family but belongs to a drug class all on its own because it’s a GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptor agonist—meaning it acts on not one but two incretin hormones that are released when you eat—and shows great promise for  weight loss.

But something we don’t discuss very often is if there’s a pill form for GLP-1s, typically subcutaneous (under-the-skin) injections. And truthfully, some of us may shy away from injecting ourselves daily or weekly with medication. So, let’s chat all about GLP-1 pills. Here’s what we know now.

Does GLP-1 come in pill form?

Yes. But right now, there’s only one FDA-approved GLP-1 pill—Rybelsus® (semaglutide). It was approved in 2019 for the treatment of type 2 diabetes mellitus. Rybelsus is made by the Danish pharmaceutical company Novo Nordisk and shares the same active ingredient as Wegovy and Ozempic—both also made by Novo Nordisk. Although a diabetes drug, Rybelsus is also prescribed off-label for weight loss in those with obesity. 

Is the GLP-1 pill as effective as injectable GLP-1 for weight loss?

Truthfully, the answer depends on the GLP-1. In a review of seven randomized controlled trials published in 2021 in Diabetes Therapy, researchers compared the efficacy data of GLP-1 injectables and the oral semaglutide pill.  The once-daily 14 mg semaglutide pill was associated with greater weight loss than the injectable GLP-1s exenatide 2 mg and lixisenatide 20 μg. 

Additionally, the review found that compared to the other GLP-1s, the oral pill performed “non-statistically significant” better than the injectables, meaning, it worked just as well as the injectables or better. The only exception was when compared against the once-weekly 1 mg injectable semaglutide, they performed just the same.

The chances of experiencing the most common side effects of nausea, vomiting, gastrointestinal issues, constipation, and diarrhea with oral semaglutide were comparable to the injectable GLP-1s, so there’s no significant difference.

Will insurance cover oral GLP-1 medications?

We’re sure you’ve read some intimidating headlines about how pricey some GLP-1 injectables can be with and without insurance. The good news is that, according to Novo Nordisk, Rybelsus is currently covered by most insurance companies. That means what you pay is entirely dependent on your insurance coverage. And keep in mind diabetes medications are typically covered by insurance when prescribed as indicated.

Moreover, the Rybelsus website has a cost estimator. The out-of-pocket cost of Rybelsus without insurance depends on where you live, the dosage you’re prescribed, and the pharmacy you visit. However, the average price for a 30-day supply is $950.45. 

Rybelsus also has a savings card available. If you’re eligible, your co-pay for the diabetes drug could be as little as $10 a month for a 30-day, 60-day, or 90-day supply. However, there are many terms and conditions to be aware of, including that you must have commercial or private insurance to qualify.

What dosages are available for oral semaglutide?

There are three dosages available of the oral semaglutide Rybelsus: 3 mg, 7 mg, and 14 mg. Novo Nordisk advises starting the oral semaglutide medication at 3 mg once daily for 30 days and then increasing it to 7 mg once daily. Patients requiring additional glycemic control can increase the dose to 14 mg once daily after taking the 7 mg dose for at least 30 days.

It’s important to note that, unlike GLP-1 injections, oral semaglutide needs to be taken “at least 30 minutes before the first food, beverage, or other oral medications of the day and that it be taken with no more than 4 ounces of plain water only,” according to the Rybelsus prescribing information by Novo Nordisk. The prescribing information also warns that if you take it with food or water, it lessens the efficacy of the oral tablet, and waiting longer than 30 minutes may actually increase the absorption of Rybelsus into your body.

Does oral semaglutide have other side effects?

As we mentioned above, the oral GLP-1 med has the same most common side effects as its injectable sister meds, but you should be aware of other serious side effects before taking the medication. 

Although extremely rare, here’s a list of negative reactions to look out for:

• Risk of thyroid C-cell tumors 
• Pancreatitis (inflammation of the pancreas)
• Diabetic retinopathy Complications (damage to the eye’s retina)
• Hypoglycemia (low blood sugar)
• Acute kidney Injury 
• Hypersensitivity 
• Acute gallbladder disease 

Rybelsus also comes with a black box warning that you shouldn’t take the medication if you have a personal or family history of medullary thyroid carcinoma (MTC) or you have multiple endocrine neoplasia syndrome type 2 (MEN 2). 

The prescribing information also details that you shouldn’t take Rybelsus if you’re pregnant or planning to become pregnant or breastfeeding. Additionally, Rybelsus is not meant for those patients with type 1 diabetes. 

It’s important to talk to your health care provider about your history and let them know about any other medications or supplements you’re currently taking.

Are other GLP-1 pills in the works?

The short answer: yes. The manufacturers Pfizer and Eli Lilly are racing to produce a GLP-1 pill. Clearly, Rybelsus has been highly successful since FDA approval, and other drug manufacturers want to follow suit. 

Eli Lilly issued a press release in December 2022 informing the public that the oral GLP-1 drug, orforglipron, will move to Phase 3 clinical trials for treating type 2 diabetes and obesity. We checked Lilly’s Clinical Development Pipeline for the latest;  as of April, 4, 2023, orforglipron is still in Phase 2 trials, so its approval date is still to be determined. 

In terms of overall timing for new meds, they go through three phases of trials to be approved by the FDA. The final phase 3 trial can take anywhere from one to four years but varies greatly from drug to drug. The FDA wants to ensure any new drug is effective, so treatments are thoroughly tested, and long-term effects are studied before FDA approval. All crucial steps when it comes to our well-being!

Like orforglipron, Pfizer’s oral GLP-1 drug, currently called “PF-07081532,” is in two phase 2 trials—one for treating type 2 diabetes and the other for the treatment of obesity. The clinical trials include 780 participants. The type 2 diabetes group must have failed metformin treatment and are receiving Rybelsus, a placebo, or PF-07081532. The obesity trial group was required to have a body mass index (BMI) of 30 or greater without type 2 diabetes; they’re receiving a placebo or PF-07081532. 

This Pfizer study began in October 2022 and is expected to end in December 2023. At that point, PF-07081532 will need to go through a third clinical trial before it can be FDA-approved for treating type 2 diabetes, obesity, or both. 

So, currently, orforglipron and PF-07081532 are neck and neck in terms of phase 2 trials. And some pharmaceutical forecasters anticipate that the GLP-1 oral tablets will be available by prescription in late 2024.  

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GLP-1*

GLP-1 prescriptions, filled through your local pharmacy, are now available as part of Found's weight-loss toolkit. While GLP-1s are effective for weight loss, they are not clinically appropriate for everyone. Eligibility for a GLP-1 is based on a thorough evaluation of your medical history, eating behavior, lab work, and insurance coverage. If a GLP-1 is not appropriate for you, our providers will work with you to determine an effective medication for your health profile.

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