The first oral GLP-1 Agonist, Rybelsus, has a problematic dosing regimen that patients must understand and be willing to follow before you prescribe it to them.

Rybelsus (reh-BEL-sus, semaglutide) is a tablet version of injectable Ozempic.¬† Glucagon-like peptide-1 (GLP-1) is inactivated in the stomach, so that’s why other GLP-1 agonists, Bydureon (exenatide), Trulicity (dulaglutide), Victoza (liraglutide), etc., are injected. Rybelsus is formulated to prevent breakdown and improve absorption. But it’s difficult¬† to take correctly like a bisphosphonate. Emphasize that Rybelsus must: be taken DAILY with a sip or no more than 4 ounces of water, at least 30 minutes before the first food, other beverage, or oral meds of the day. Not doing so reduces efficacy. Keep in mind that Bydureon, Ozempic, and Trulicity are injected WEEKLY, at any time of day, with or without meals. In making your decision, weigh current CV data. So far, evidence isn’t strong enough to say that Rybelsus lowers CV risk in type 2 patients with CV disease or at high CV risk, even though Ozempic does. Still, you can expect Rybelsus to sound appealing to some patients. For example, it lowers A1C by about 1% and leads to short-term weight loss of about 4 to 9 pounds, in the same range as injectable GLP-1 agonists. But GI side effects may last longer when starting Rybelsus, likely because it’s titrated monthly, slower than most injectables. Rybelsus will cost about $770/month, versus $620 to $920 for injectables. Since it is new it may not be preferred by payers. Consider saving Rybelsus for type 2 patients without CV disease or high CV risk who want an oral medication, and who can follow its unusual administration.

Lancet 2019;394(10192):39-50; N Engl J Med 2019;381(9):841-51; Diabetes Care 2019;42(9):1724-32; Diabetes Technol Ther Published online Oct 1, 2019; doi:10.1089/dia.2019.0185