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GLP-1 RA Formulations

CE / CME

Pioneering a New Therapy: An Oral GLP-1 for Type 2 Diabetes

Physicians: Maximum of 0.25 AMA PRA Category 1 Credit™

Nurses: 0.25 Nursing contact hour

Released: October 22, 2020

Expiration: October 21, 2021

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Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been available for the treatment of type 2 diabetes for several years. They have excellent efficacy and are associated with a low risk of hypoglycemia and significant weight loss. Some members of the class are also indicated to reduce the risk of cardiovascular disease. Despite these positive attributes, utilization of GLP-1 RAs has remained relatively low. There are many possible reasons for this, but one barrier for both patients and some providers has undoubtedly been the need for injection.

Oral Semaglutide
Recently, an oral version of the GLP-1 RA semaglutide was approved by the FDA. This is a significant breakthrough, as it is the first time a peptide drug has been successfully developed for oral administration. Formulating a peptide for oral administration is challenging because these molecules rapidly degrade in the acidic environment of the upper gastrointestinal tract and because absorption of large molecules across the gastrointestinal epithelium is poor. Because semaglutide is formulated with the absorption enhancer sodium N-(8-2-hydroxybenzoyl amino) caprylate (SNAC), it is protected from proteolytic degradation in the stomach, and absorption across the gastric mucosa is facilitated.

Daily Dosing
In contrast to the once-weekly subcutaneous formulation, oral semaglutide is taken daily. Because food and/or large volumes of fluid in the stomach reduce the gastric absorption of oral semaglutide, patients are advised to take oral semaglutide in the morning in a fasted state with no more than 120 mL (4 oz) of water and wait at least 30 minutes before taking any food, drink, or other oral medication.

Oral semaglutide is initiated at a dose of 3 mg/day and titrated to a dose of 7 mg/day after 4 weeks. The dose can be further titrated to 14 mg/day after an additional 4 weeks if patients are not at goal and if tolerated.

Clinical Studies
The oral semaglutide phase III development program involved 10 randomized, placebo- and active-controlled trials and included more than 9500 patients on a range of background therapies. Across these trials, oral semaglutide was associated with reductions in A1C from 1% to 2%, decreases in body weight from 2.6 to 4.4 kg, and a low rate of hypoglycemia. Compared with active controls, oral semaglutide provided significantly better efficacy than the dipeptidyl peptidase 4 inhibitor sitagliptin, the sodium-glucose cotransporter-2 inhibitor empagliflozin, and the GLP-1 RAs liraglutide and dulaglutide, which are administered subcutaneously.

Oral semaglutide was generally well tolerated. As is typical of the class, the most frequent adverse events occurring in patients receiving oral semaglutide were gastrointestinal (nausea, vomiting, diarrhea, and constipation), transient, and generally mild to moderate in severity. The cardiovascular safety of oral semaglutide was demonstrated in a dedicated study (PIONEER 6) in patients with type 2 diabetes with cardiovascular disease or high cardiovascular risk.

Collectively, data from the oral semaglutide development program suggest that it is a highly efficacious, safe, and well tolerated therapeutic approach for the treatment of type 2 diabetes. Because injections remain a barrier for many patients, the availability of oral semaglutide allows providers to prescribe GLP-1 RA therapy to a broader population and may facilitate earlier adoption of GLP-1 RA treatment.

Your Thoughts
Have you begun using oral semaglutide in your clinic? Join the conversation by answering the poll question or leaving a comment.

And for more support on selecting the ideal GLP-1 RA, I encourage you to visit the Interactive Decision Support Tool, Choosing Among GLP-1 Receptor Agonists for Patients With Type 2 Diabetes, which I developed with my colleagues, Martin J. Abrahamson, MD, FACP; Zachary T. Bloomgarden, MD, MACE; Anne Peters, MD; and Robert S. Zimmerman, MD. In this online tool, you can enter the details of your patient and learn how 5 experts would proceed.

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How will the availability of an oral GLP-RA change your clinical practice?
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