Oral GLP-1RA non-inferior to placebo in reducing MACE in T2DM with high CV risk

ADA 2019 Oral formulation of GLP-1RA semaglutide was not inferior to placebo with regard to major adverse cardiac events in T2DM patients with high CV risk.

Use of oral glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide, a first tablet version of a GLP-1RA, was non-inferior to placebo in reducing major adverse cardiac events (MACE) in type 2 diabetes (T2DM) patients with high CV risk, as demonstrated in the PIONEER 6 trial. These results were presented at the American Diabetes Association’s 79th Scientific Sessions in San Francisco, CA, USA.

PIONEER 6 was a randomized controlled trial conducted across 21 countries, including 3183 patients who either received 14 mg of semaglutide (n=1591) or placebo (n=1592). Patients had an average age of 66 years, 85% was ≥50 years and had established CVD or CKD (n=2695) and 15% was ≥60 years with CV risk factors (n=488). Primary endpoint was time to first MACE, including CV death, non-fatal MI or non-fatal stroke. Median follow up was 15.9 months.

MACE occurred in 3.8% of patients in the oral semaglutide group and 4.8% in the placebo group (HR 0.79, 95%CI: 0.57-1.11, P<0.001 for noninferiority). Outcomes for CV death were 0.9% in the oral semaglutide group and 1.9% in the placebo group (HR 0.49, 95%CI: 0.27-0.92), non-fatal MI occurred 2.3% in the semaglutide group and 1.9% in the placebo group (HR 1.18, 95% CI 0.73-1.90), non-fatal stroke occurred 0.8% in the semaglutide group vs. 1.0% in the placebo group (HR 0.74, 95%CI 0.35-1.57). Death from any cause occurred in 1.4% in the oral semaglutide group and 2.8% in those who received placebo (HR 0.51, 95%CI 0.31-0.84).

Other trials in the PIONEER program have examined effects of oral semaglutide in comparison to other medications (sitagliptin, empagliflozin and liraglutide) or placebo. The results of these trials have demonstrated that oral semaglutide is effective, safe and tolerable. Compared to oral DPP-4 inhibitor sitagliptin, oral semaglutide resulted in greater reduction of HbA1c in T2DM patients.

“By eliminating the barrier of an injection, oral semaglutide has the potential for widespread use in the treatment of type 2 diabetes including in high-risk patients with cardiovascular disease and chronic kidney disease,” said lead investigator Mansoor Husain, MD, director of the Toronto General Hospital Research Institute; executive director of the Ted Rogers Centre for Heart Research; and professor of medicine at the University of Toronto.

“Oral semaglutide is currently under review by the FDA, the EMA and Health Canada,” said chief investigator John Buse, MD, PhD, Verne S. Caviness Distinguished Professor, chief of the division of endocrinology, director of the NC Translational and Clinical Sciences Institute, and the executive associate dean of clinical research at the University of North Carolina School of Medicine in Chapel Hill.

Source: press release ADA, June 11, 2019The results of the PIONEER 6 trial were simultaneously published in NEJM.