Greater Combined Reductions of HbA(1c) ≥ 1.0% and Body Weight Loss ≥ 5.0% or ≥ 10.0% with Orally Administered Semaglutide Versus Comparators

INTRODUCTION: A post hoc analysis of the PIONEER 1–5 and 8 trials assessed the clinically relevant composite endpoints of HbA(1c) (glycated haemoglobin) reduction ≥ 1% and body weight loss of ≥ 5% or ≥ 10% with orally administered semaglutide versus comparators. METHODS: In the PIONEER trials, people with type 2 diabetes were randomised to orally administered semaglutide versus placebo (PIONEER 1, 4, 5 and 8), empagliflozin (PIONEER 2), sitagliptin (PIONEER 3) and liraglutide (PIONEER 4) for 26–78 weeks. This analysis assessed the proportion of people achieving an HbA(1c) reduction of ≥ 1% and body weight loss of ≥ 5% at week 26 and at end of treatment, and the proportion of people achieving an HbA(1c) reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment. RESULTS: Overall, 3506 people in PIONEER 1–5 and 8 were included. At week 26 and at end of treatment, odds of achieving the composite endpoint of an HbA(1c) reduction of ≥ 1% and body weight loss of ≥ 5% were significantly greater with orally administered semaglutide 14 mg than with placebo (PIONEER 1, 4, 5 and 8; all p < 0.0001), empagliflozin 25 mg (PIONEER 2, p < 0.0001), sitagliptin 100 mg (PIONEER 3, p < 0.0001) and liraglutide 1.8 mg (PIONEER 4, p < 0.0001). Odds of achieving the composite endpoint of HbA(1c) reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment were also significantly greater with orally administered semaglutide versus comparators. CONCLUSION: In PIONEER 1–5 and 8, odds of achieving clinically relevant reductions in both HbA(1c) and body weight were significantly greater with orally administered semaglutide versus comparators. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13300-023-01413-5.