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Oral semaglutide (Rybelsus°): more uncertainty than with subcutaneous liraglutide

FEATURED REVIEW Semaglutide was first authorised in the European Union as a solution for weekly subcutaneous injections. It was authorised more recently in oral tablet form. How do Prescrire's editors rate this new product?
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  •  NOTHING NEW  In a trial in 711 patients with type 2 diabetes, oral semaglutide (a GLP-1 receptor agonist) was no more effective at lowering blood glucose levels than subcutaneous liraglutide (another GLP-1 receptor agonist). The results of a placebo-controlled trial in about 3200 patients with high HbA1c levels suggested that adding oral semaglutide to glucose-lowering therapy reduces mortality, but they are not sufficiently robust to base decisions upon. The results of another placebo-controlled trial, in about 9500 patients at high risk of cardiovascular events, are expected in 2024. The drug’s oral route of administration is an advantage. But the gastrointestinal absorption of semaglutide is highly variable, despite a novel excipient, making its oral use riskier than subcutaneous use. In practice, as of early 2021, when a GLP-1 receptor agonist is considered worthwhile, liraglutide is a better choice, despite the fact that it requires daily subcutaneous injections. The results obtained with subcutaneous liraglutide in the prevention of cardiovascular events are more robust and there is longer experience in clinical use. 

©Prescrire 1 June 2021

Source: "Oral semaglutide (Rybelsus°). More uncertainty than with subcutaneous liraglutide" Prescrire International 2021; 30 (227): 148-150. Subscribers only.

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