Integrating oral semaglutide into clinical practice in primary care: for whom, when, and how?

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ABSTRACT

Oral semaglutide is the first US Food and Drug Administration-approved oral glucagon-like peptide-1 receptor agonist (GLP-1RA) for the treatment of type 2 diabetes (T2D). Prior articles within this supplement reviewed the PIONEER trial program, which demonstrated that oral semaglutide reduced glycated hemoglobin and body weight when given to patients with uncontrolled T2D on various background therapies, and had a safety profile consistent with subcutaneous GLP-1RAs. This article provides guidance on integrating oral semaglutide into clinical practice in primary care. Patient populations with T2D who may gain benefit from oral semaglutide include those with inadequate glycemic control taking one or more oral glucose-lowering medication (e.g. after metformin), patients for whom weight loss would be beneficial, patients at risk of hypoglycemia, those who would historically have been considered for treatment with a subcutaneous GLP-1RA, and those receiving basal insulin who require treatment intensification. Like other GLP-1RAs, oral semaglutide is contraindicated in those with personal/family history of medullary thyroid carcinoma, and in those with multiple endocrine neoplasia syndrome type 2, as noted in a boxed warning in the prescribing information. Oral semaglutide has not been studied in those with a history of pancreatitis, is not recommended in patients with suspected/confirmed pancreatitis, and is not indicated in type 1 diabetes. When initiating oral semaglutide, gradual dose escalation is recommended to minimize the risk of gastrointestinal adverse events. As food and excess liquid reduce oral semaglutide absorption, patients should swallow the tablet with up to 4 fl oz/120 mL of water on an empty stomach upon waking, and should wait at least 30 minutes before eating, drinking, or taking other oral medications. Those managing patients should be aware of the potential impact of these dosing conditions on concomitant medications. When counseling patients, it is important to discuss these administration instructions, realistic therapeutic expectations, and strategies for mitigation of gastrointestinal events. Oral semaglutide provides a new option for add-on to initial T2D therapy (or later in the treatment paradigm), with the potential to enable more patients to benefit from the improvements in glycemic control, reductions in body weight, and low risk of hypoglycemia afforded by GLP-1RAs.

KEYWORDS:

• Oral semaglutide
• type 2 diabetes
• clinical practice
• primary care
• glucagon-like peptide-1 receptor agonist
• guidelines

Acknowledgments

Under the direction of the authors, medical writing and editorial support were provided by Nicola Beadle of Axis, a division of Spirit Medical Communications Group Ltd. (funded by Novo Nordisk Inc.). The authors were involved with drafting the outline and critically editing all drafts during the development of the article, and all authors provided their final approval for submission.

Declaration of interest

S.A.B. has received speaker honoraria from AstraZeneca, Bayer, Janssen, and Novo Nordisk; consultant honoraria from Abbott, AstraZeneca, Bayer, Eli Lilly and Company, Janssen, Novo Nordisk, and Sanofi US.

O.M. has served on advisory boards for AstraZeneca, Boehringer Ingelheim, BOL Pharma, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, and Sanofi; received a research grant paid to her institution from AstraZeneca and Novo Nordisk; and has been a member of the speaker’s bureau for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, and Sanofi.

E.E.W. has received research support from Abbott; serves on advisory boards for Abbott, Boehringer Ingelheim, Eli Lilly, and Voluntis; and consults for Bayer, Boehringer Ingelheim, Eli Lilly, and Mannkind.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This peer reviewed article was supported by Novo Nordisk Inc.; the company was provided with the opportunity to perform a medical accuracy review.