Injectable GLP-1 Agonist Semaglutide Gets CVD Event Reduction Indication

An injectable formulation of the glucagon-like peptide-1 (GLP-1) analogue semaglutide (Ozempic) is now approved by the US Food and Drug Administration for the reduction of major adverse cardiovascular events in patients with type 2 diabetes, according to an announcement from the manufacturer Novo Nordisk.

Specifically, semaglutide is indicated for reducing the risk of cardiovascular death, nonfatal MI, or nonfatal stroke in adults with type 2 diabetes and established cardiovascular disease on the basis of the SUSTAIN-6 randomized trial.

In that study of 3,297 subjects, the majority of whom had cardiovascular disease, chronic kidney disease, or both, treatment with semaglutide on top of usual care reduced the risk of MACE by 26% compared with usual care plus placebo after a median follow-up of 2.1 years. Overall, the primary outcome occurred in 8.9% of patients treated with placebo and 6.6% of patients treated with semaglutide (P < 0.001 for noninferiority; P = 0.02 for superiority).

The subcutaneous injection of semaglutide was approved for glycemic control in patients with type 2 diabetes in 2017. It is now the second GLP-1 agonist approved for the reduction of clinical events. In 2017, the FDA awarded an expanded indication for liraglutide (Victoza; Novo Nordisk) to include the reduction of cardiovascular death, MI, or stroke. Several sodium glucose co-transporter 2 (SGLT2) inhibitors have also been approved for reducing cardiovascular events.  

The label for the oral formulation of semaglutide (Rybelsus) also received an update from US regulators, with the FDA adding information to indicate the agent is safe based on data from the PIONEER 6 cardiovascular outcomes study. The updated label is not an expanded claim for cardiovascular benefit. In PIONEER 6, oral semaglutide was noninferior to placebo with respect to the primary endpoint of cardiovascular death, MI, or stroke when added on top of usual care.