COMMENTARY

Oral Semaglutide Brings GLP-1s to Primary Care

Anne L. Peters, MD

Disclosures

November 21, 2019

This transcript has been edited for clarity.

Today I'm talking about oral semaglutide. We're used to once-weekly semaglutide, but now we have this oral form that's making its way into the marketplace.

It's important because it may expand the use of GLP-1 receptor agonist therapy into primary care in ways that haven't been done before. And hopefully, more patients can benefit from this class of drug.

What I find interesting is how this medication is formulated. Oral semaglutide is coformulated within a tablet that has an absorption enhancer. This absorption enhancer is sodium N-[8-(2-hydroxybenzoyl)amino] caprylate, or SNAC, for short. SNAC facilitates semaglutide absorption in the stomach by increasing the local pH, which leads to increased drug solubility and protects against proteolytic degradation.

The stomach is obviously very acidic, and that breaks down all of these peptide hormones, so you can't give them orally. SNAC helps to create an interesting kind of microenvironment within the stomach mucosa that allows for absorption of semaglutide or any other large molecule that you mix with it, so now you get a circulating level of the hormone.

This is a new and seemingly effective way of giving a GLP-1 receptor agonist. There have been many trials now published, with a number of them presented at the American Diabetes Association meetings this past June.

Similar Benefits, Similar Risks

The studies of the PIONEER program were designed to compare oral semaglutide with a whole host of other agents, including sitagliptin, monotherapy versus placebo, and pretty much everything else. These studies demonstrated a very similar reduction in A1c to what you'd see with injected semaglutide, and you also get weight loss.

This is pretty similar in efficacy to the injected form of semaglutide. You do, however, get the same side effects. There's a black box warning with oral semaglutide, just like with injected semaglutide, for a concern for medullary thyroid carcinoma. It's recommended that patients with a personal or family history of medullary thyroid carcinoma or MEN syndrome should not take this agent.

The more common issues are those regarding gastrointestinal (GI) side effects. Patients with oral semaglutide experience the same GI side effects that we're familiar with following any GLP-1 receptor agonist therapy. These side effects include nausea, vomiting, diarrhea, and sometimes constipation. That's why we need to start at a low dose of oral semaglutide and work up just like we tend to do with the injectable GLP-1 receptor agonists.

How Are They Taken?

Oral semaglutide comes in a blister pack. It's important that patients keep the pills in the blister pack. They should not cut them open with scissors but rather push up each individual pill when they need it. Do not crush or split the pills. They have to take the pills whole.

When a patient is taking oral semaglutide, they need to be fasting. Patients take this first thing in the morning after they haven't eaten or drank overnight, and they must take them with a very small amount of water—4 oz or less. We don't want them to wash the pill out of their stomach because then they're not going to absorb the oral semaglutide.

Patients need to wait at least 30 minutes before putting anything else in their stomach, including other fluids, medications, or food. That wait allows for this little microenvironment to happen so the oral semaglutide is absorbed and gets into the bloodstream.

In order to reduce the rate of side effects, there's a starter dose of oral semaglutide, which is 3 mg. A patient takes a 3-mg tablet every morning for a month. Then if they're tolerating it, you go up to the 7-mg tablet. If that tablet is enough to achieve the desired clinical response, you keep the patient there. If not, you can go up to the 14-mg tablet, which is the maximum dose, and they take one of those every morning.

Should Patients Be Switching?

I'm excited about this because I think we're expanding the ability of a GLP-1 receptor agonist to be used in primary care. I have many patients on injectable GLP-1 receptor agonist therapy and I'm not sure that I want to be switching them to an oral form, unless they want one.

Going forward, for patients who are new to semaglutide, I'll offer them the choice of either oral semaglutide or injected, with the caveat that, of course, it takes a while for insurance coverage to kick in for newer forms of older agents. I want to make sure that I'm not offering something for which a patient doesn't have full coverage.

Theoretically, I think offering patients a choice of an oral medication taken in the way I've described, or an injection once a week, makes sense. I see the oral form and the once-weekly, injected form as pretty similar in terms of patient outcomes.

Hopefully, this is a new tool that will be instrumental in helping your patients. I look forward to learning about what this feels like in practice and expanding the availability of a GLP-1 receptor agonist in primary care.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California (USC) Keck School of Medicine and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts and three books on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

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