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

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 asubcutaneous 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 aboxed warning in the prescribing information. Oral semaglutide has not been studied in those with ahistory 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.

A 2021 Update on the Use of Liraglutide in the Modern Treatment of ‘Diabesity’: A Narrative Review

“…Long-acting GLP-RAs are liraglutide (Victoza, Saxenda), once-weekly exenatide (Bydureon), dulaglutide (Trulicity), albiglutide (Eperzan, Tanzeum), semaglutide (Ozempic), and oral semaglutide (Rybelsus). GLP-1 RAs approved for use in T2DM treatment are summarized in Table 2 [ 33 , 34 , 35 ].…”

New Incretin Combination Treatments under Investigation in Obesity and Metabolism: A Systematic Review

“…The most frequent side effects were dose-related nausea and diarrhea [ 17 ]. Semaglutide should not be used in patients with history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, as it increases the risk for thyroid c-cell carcinoma [ 48 ]. Contraindications are similar to liraglutide and the rest of the GLP-1 agonists since they have equal mechanisms of action.…”

The efficacy and safety of oral semaglutide for glycaemic management in adults with type 2 diabetes compared to subcutaneous semaglutide, placebo, and other GLP-1 RA comparators: A systematic review and network meta-analysis

“…However, it is important to note that the use of oral semaglutide is generally not recommended or requires special consideration for women who are pregnant or breastfeeding and for children with T2D. In addition, oral semaglutide is not indicated for people with type 1 diabetes or patients with diabetic ketoacidosis [ 45 ].…”