Discussing Upcoming Oral GLP-1 for Treating Type 2 Diabetes

Although I feel the conversation regarding specialty drugs and potential regulatory changes in the near future for managed care have dominated, there are still upcoming changes to traditional drug categories that are quite exciting in my mind. One of these is the development and potential near-future release of oral semaglutide, a glucagon-like peptide-1 (GLP-1) drug.

Ever since I learned about GLP-1 drugs—their mechanism, how robust they can be in lowering blood glucose, and the number of beneficial effects they can offer beyond lowering glucose levels—I placed this class of drugs as my recommended second line offering (behind metformin) for the majority of type 2 diabetes patient I treat. When one of my own close family members expressed frustration in trying to lower her A1c, I helped her start on the GLP-1 product covered by her health plan, and it has helped her achieve and remain under her A1c goals ever since.

The main drawback for the current GLP-1 medications on the market that many of us have likely encountered is that they come in injectable forms only. While the auto-injector devices available for these drugs help a number of patients overcome their needle aversion, I still encounter a number of patients who fear needles enough to avoid this class.

I am sure most of our readers understand how peptides (like those that make GLP-1 medications) are quickly broken down in the stomach due to acid and other enzymatic degradation processes, requiring peptide medications to be given via a non-oral route. Knowing this led me to have little hope for patients with type 2 diabetes and severe needle phobia being able to take advantage of GLP-1 medications.

That all changed when I began hearing about the development of oral semaglutide. The chemistry behind this oral option, in my mind, strikes the elegant goal of scientific development—it is effective while being relatively simple.

The peptide medication is co-formulated with a molecule engineered to help with absorption called sodium N-[8-(2-hydroxybenzoyl) aminocaprylate], or SNAC for short. The SNAC molecule provides a local buffering effect in the stomach, protecting the peptide from degradation. This buffering in the stomach also means that the majority of the absorption of the medication will take place in the stomach rather than in the intestinal tract.

The use of SNAC with semaglutide looks to be a success based on the research Novo Nordisk has been performing in clinical trials. Novo has released some of the data from the clinical trials of oral semaglutide at recent medical conferences and more results are expected to be released at upcoming conferences this year. While an in-depth look into the trials, design, results, and an analysis of what they might mean for our populations is warranted; I will save that discussion for when we near the time of potential approval.

I will say, that based on the data I have had a chance to look at, I believe the efficacy and safety profile will likely be seen by the medical community to be in line with the other GLP-1 medications on the market. I believe this will mean that the clinical decision making surrounding oral semaglutide vs other GLP-1 offering will mostly come down to injectable vs oral and frequency of administration.

Novo Nordisk filed a new drug applications with the food and drug administration (FDA) for oral semaglutide in late march for the treatment of type 2 diabetes and for cardiovascular risk reduction in patients with type 2 diabetes. The application for the treatment of type 2 diabetes was filed with a priority review voucher meaning that we should see a decision from the FDA by early fall. If approved, I would expect to see oral semaglutide available on the market by early 2020.

While the introduction of oral semaglutide may lead to some complications within managed care from a rebate perspective—Will the oral version get included in the market baskets of other GLP-1 medications? Does a particular plan have contracts that are written based on the number of products or number of manufacturers? —I personally believe the reception and uptake of this product will be relatively quick. The availability of an oral option will be great news to patients wanting to avoid injectable drugs, and I think providers already comfortable with today’s GLP-1 offerings will be happy to prescribe an oral option. It will be interesting to watch for the additional trial data for oral semaglutide and to see the final FDA decision in the next few months.

Russ J Spjut, PharmD, is owner of Formulary Intel Consulting. He is a residency trained pharmacist in managed care with experience in both commercial and Medicare Part D PBM operations. He has been involved in formulary management, P&T committee presentations, clinical program development, formulary strategy, clinical analysis, client management, and review of coverage determination requests for a major health care management company.