The Food and Drug Administration (FDA) has approved the first oral glucagon-like peptide-1 (GLP-1) receptor agonist to treat type 2 diabetes: semaglutide under the trade name Rybelsus. Until now, all GLP-1 receptor agonists were administered via subcutaneous injection once or twice daily or weekly, depending on the drug. Semaglutide was previously approved in a subcutaneous form under the trade name Ozempic. Other previously approved GLP-1 receptor agonists include dulaglutide (Trulicity), exenatide (Byetta), exenatide ER (Bydureon), liraglutide (Victoza), and lixisenatide (Adlyxin).

GLP-1 receptor agonists are also referred to as incretin mimetics. These drugs stimulate insulin secretion in response to rising postprandial blood glucose levels. The drugs also slow the absorption of food from the intestine, prolonging a feeling of fullness.

In a placebo-controlled, double-blind study, 703 patients with type 2 diabetes that hadn't been controlled by diet and exercise were randomized to receive Rybelsus 3 mg, 7 mg, or 14 mg, or a placebo. The 7-mg and 14-mg Rybelsus doses were found to decrease glycated hemoglobin (HbA_1c) significantly more than placebo. A HbA_1c of less than 7% was achieved in 69% of patients receiving 7 mg, in 77% of patients receiving 14 mg, but in only 31% of those receiving placebo.

The most common adverse effects of Rybelsus are nausea, diarrhea, vomiting, decreased appetite, indigestion, and constipation. Possible serious adverse effects include pancreatitis, vision changes, hypoglycemia if taken with other antihyperglycemic drugs, kidney failure, and allergic reactions.

Animal studies have shown that semaglutide can produce thyroid C-cell tumors, including medullary thyroid cancer, in rodents. For this reason, Rybelsus carries a boxed warning of the risk of these tumors.

Because Rybelsus slows gastric emptying, it may interact with other oral drugs. Peak circulating levels occur 60 minutes after administration. It takes four to five weeks of daily administration to reach steady state. The drug has an elimination half-life of about one week; thus, after discontinuation, it takes about five weeks for Rybelsus to disappear from the circulation.

Nurses and NPs should instruct patients to take Rybelsus with no more than 4 ounces of plain water at least 30 minutes before their first meal, beverage, or other oral medication of the day to minimize interference with absorption. Because of the long washout period, women should use effective birth control for two months after discontinuing Rybelsus to prevent fetal exposure (although no risks to fetal outcomes have been identified).

For complete prescribing information, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/213051s000lbl.pdf.