Is there an oral GLP-1 agonist? Yes, and more are on the way

Is there an oral GLP-1 agonist? Yes, and more are on the way

Is there an oral GLP-1 agonist? Yes, and more are on the way

More convenient and needle-free GLP-1 options are coming, and the studies show they are as effective, if not more, compared to GLP-1 injectables

The Found Team
Last updated:
August 23, 2023
5 min read
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Does the thought of injecting medication into your body send shivers down your spine? You’re not alone: An estimated 25 percent of adults are afraid of needles. 

And if you’re interested in a GLP-1 medication like Wegovy® for weight loss, the fact that it’s an injectable might be a deal-breaker. Most GLP-1s* are taken by subcutaneous injection, including the two that are approved by the FDA to treat obesity: Wegovy and Saxenda®.

But there’s some good news for the needle-averse: The FDA has already approved one oral GLP-1 agonist, and more are being developed for obesity specifically. Even if shots don’t bother you, oral medications can be more convenient than GLP-1 injectables: Pills are easy to pack and store and don’t require careful needle or pen disposal.

What oral medication is like Ozempic® or Wegovy?

Right now, there’s only one oral GLP-1 agonist: Rybelsus® daily tablets. It has the same active ingredient, semaglutide, found in injectable Wegovy and Ozempic. All three medications are made by the pharmaceutical company Novo Nordisk. 

Wegovy is FDA-approved to treat obesity, while Ozempic and Rybelsus are approved to treat type 2 diabetes. Both Ozempic and Rybelsus can also be prescribed off-label to treat obesity. Off-label prescribing is a common practice by which clinicians prescribe an FDA-approved drug at different doses or for reasons other than what the drug is approved to treat. 

What oral GLP-1 agonists are on the horizon?

Rybelsus might not be the only oral GLP-1 medication for long, though. Two other pharmaceutical companies have their own oral GLP-1 drugs in the works: 

  •  Orforglipron: Developed by Eli Lilly, it’s in Phase 3 clinical trials for treating type 2 diabetes and obesity, with an expected September 2025 completion. Before FDA approval, new drugs usually undergo three phases of clinical trials to ensure they’re effective. Depending on the drug, Phase 3 can take one to four years. 
  •  Danuglipron: Developed by Pfizer and intended to keep blood glucose at healthy levels, this oral GLP-1 recently completed Phase 2 clinical trials for the treatment of type 2 diabetes and obesity. It will still have to go through Phase 3 clinical trials before FDA approval. 

Remind me: How do GLP-1s work? 

Whether taken by pill or injection, GLP-1 drugs can be a life-changing treatment for people with type 2 diabetes and/or obesity.      

GLP-1 medications mimic the glucagon-like peptide 1 hormone your body makes naturally, which helps stimulate the release of insulin to regulate blood sugar. 

The GLP-1 hormone also slows digestion, inhibits the release of glucagon (another hormone that regulates blood glucose), and helps signal to your brain when you’ve had enough to eat.

GLP-1 medications are designed to bind to cells in your body that have GLP-1 receptors, just like your natural GLP-1 hormone would. They’re meant to be used, along with lifestyle changes such as diet and exercise, under a health care provider’s supervision. 

What are the potential side effects of GLP-1s? 

Common side effects include (but are not limited to) nausea, vomiting, gastrointestinal issues, and headaches. Rarely, they may lead to severe nausea or vomiting, which could result in more serious complications. With injectible GLP-1s, local reactions like itchiness or redness may occur at the injection site.

It's crucial to discuss medical history and potential risks with a health care provider before using these medications, as these drugs are not suitable for people with certain medical conditions, including those with a history of medullary thyroid cancer, type 1 diabetes, pancreatitis, or severe gastrointestinal disease. Pregnant or breastfeeding women also should not use them. Find more detailed side effect and risk information for specific medications by name here

Is oral semaglutide as effective as injectable weight loss medication?

Yes, according to recent research. Studies show that, at the right dosage, oral semaglutide agonists are as effective as injectables. In a systematic review of seven randomized controlled trials for people with type 2 diabetes published in Diabetes Therapy, researchers compared the efficacy data of GLP-1 injectable medications to the oral semaglutide pill. A 14 mg semaglutide pill form was associated with more weight loss than the injectable GLP-1s lixisenatide (which is no longer on the market in the United States) and exenatide. The same review found that a daily oral semaglutide pill was as effective as a once-weekly 1 mg shot of semaglutide for weight loss.

One of the other oral GLP-1s on the horizon, Pfizer’s danuglipron pill, led to a similar weight loss as injectable semaglutide according to results recently released from Phase 2 clinical trials. These trials included 411 participants with type 2 diabetes who took oral danuglipron or a placebo twice a day. After 16 weeks, participants in the danuglipron groups lost significantly more body weight than those in the placebo group. 

Research on Eli Lilly’s orforglipron is ongoing, so efficacy data isn’t available yet.

Will oral GLP-1 agonists be cheaper or covered by Medicare and Medicaid?

It’s hard to say. As of right now, the cost of Rybelsus is in line with injectable medications. Newer drugs are often more expensive because developers seek to recoup development costs. GLP-1s generally have a hefty price tag and can start at $800 or more a month, and most private insurers don’t cover these medications for weight loss. 

Although there’s been a push for Medicare to include weight-loss medications, it currently does not cover them. Adding coverage for semaglutide would cost Medicare $26.8 billion annually, and insurance premiums likely would go up, according to a study published in the New England Journal of Medicine. Medicaid, however, can cover obesity-related services, including body mass index (BMI) screening, education, nutrition and physical activity, counseling, prescription drugs that promote weight loss, and bariatric surgery as appropriate—depending on the state you live in. 

What the future of GLP-1s may look like

An oral GLP-1 agonist might be a more attractive option. Many people are more familiar with oral medications and prefer the simplicity of taking a pill versus giving themselves an injection. That said, some GLP-1 injectables are once a week, which some may find more convenient than having to remember to take a pill each day. 

One more thing to consider is whether or not oral GLP-1 agonists obtain FDA approval for obesity. The only oral GLP-1 medication on the market, Rybelsus, is currently FDA-approved for type 2 diabetes. Wegovy and Saxenda, both injectables, are the only GLP-1s FDA-approved for obesity. There’s also cost and health insurance coverage to consider. But all in all, the future looks promising as more oral GLP-1 agonists are in the pipeline.  

*Access to GLP-1s prescriptions is now available as part of Found's weight-loss program. 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 medical history, eating behavior, lab work, and insurance coverage. If a GLP-1 is not appropriate or affordable for you, Found providers can help determine if another effective medication is.

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Published date:
August 23, 2023
Meet the author
The Found Team
The Found Team

Sources

  • Novo Nordisk. Jan 2023. Rybelsus | Semaglutide Tablets. Prescribing Information. https://www.novo-pi.com/rybelsus.pdf
  • Hughes, S., & Neumiller, J. J. (2019). Oral Semaglutide. Clinical Diabetes, 38(1), 109–111. https://doi.org/10.2337/cd19-0079
  • A Study of Daily Oral Orforglipron (LY3502970) Compared With Insulin Glargine in Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk - Full Text View - ClinicalTrials.gov. (n.d.). https://clinicaltrials.gov/ct2/show/NCT05803421
  • Pfizer. 10 July 2022. A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Multiple Escalating Oral Doses of PF-07081532 in Adults With Type 2 Diabetes Mellitus. https://www.pfizer.com/sites/default/files/plsr-studies/C3991002%20Plain%20Language%20Study%20Results%20Summary%20%28PLSRS%29%20Phase%201%20PK%20Primary%20Endpoint.pdf
  • U.S. National Library of Medicine. 13 Mar 2023. Trial to Learn About the Study Medicine (PF-07081532) and Rybelsus in People With Type 2 Diabetes and Separately PF-07081532 in People With Obesity. https://clinicaltrials.gov/ct2/show/NCT05579977?term=PF-07081532&draw=2
  • Chubb, B., Gupta, P., Gupta, J. et al. (2021). Once-Daily Oral Semaglutide Versus Injectable GLP-1 RAs in People with Type 2 Diabetes Inadequately Controlled on Basal Insulin: Systematic Review and Network Meta-analysis. Diabetes Therapy: 12, 1325–1339. https://link.springer.com/article/10.1007/s13300-021-01034-w#citeas
  • Saxena, A. R., Frias, J. P., Brown, L. S., Gorman, D. N., Vasas, S., Tsamandouras, N., & Birnbaum, M. J. (2023). Efficacy and Safety of Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist Danuglipron for Glycemic Control Among Patients With Type 2 Diabetes. JAMA Network Open, 6(5), e2314493. https://doi.org/10.1001/jamanetworkopen.2023.14493
  • Moody, C. (2021b). Does Medicare Cover Weight Loss Medication? Medicare & Medicare Advantage Info, Help and Enrollment. https://www.medicare.org/articles/does-medicare-cover-weight-loss-medication/
  • Baig, K., Dusetzina, S. B., Kim, D. D., & Leech, A. A. (2023). Medicare Part D Coverage of Antiobesity Medications — Challenges and Uncertainty Ahead. The New England Journal of Medicine, 388(11), 961–963. https://doi.org/10.1056/nejmp2300516
  • Medicaid Can Cover Obesity-Related Services, Helping Beneficiaries Reduce the Risk of Chronic Disease | Medicaid. (n.d.-b). https://www.medicaid.gov/about-us/program-history/medicaid-50th-anniversary/entry/47693
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