Greater Combined Reductions of HbA1c ≥ 1.0% and Body Weight Loss ≥ 5.0% or ≥ 10.0% with Orally Administered Semaglutide Versus Comparators

Kathleen M Dungan; Lars Bardtrum; Erik Christiansen; Johanna Eliasson; Linda Mellbin; Vincent C Woo; Tina Vilsbøll

doi:10.1007/s13300-023-01413-5

Greater Combined Reductions of HbA_1c ≥ 1.0% and Body Weight Loss ≥ 5.0% or ≥ 10.0% with Orally Administered Semaglutide Versus Comparators

Diabetes Ther. 2023 Aug;14(8):1415-1425. doi: 10.1007/s13300-023-01413-5. Epub 2023 May 31.

Authors

Kathleen M Dungan¹, Lars Bardtrum², Erik Christiansen², Johanna Eliasson², Linda Mellbin³, Vincent C Woo⁴, Tina Vilsbøll⁵

Affiliations

¹ Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, 1581 Dodd Drive, Columbus, OH 43210, USA. kathleen.dungan@osumc.edu.
² Novo Nordisk A/S, Søborg, Denmark.
³ Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
⁴ Section of Endocrinology and Metabolism, University of Manitoba, Winnipeg, MB, Canada.
⁵ Clinical Research, Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark.

Abstract

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.

Keywords: Body weight loss; Composite endpoint; Glucagon-like peptide 1 analogue; Glycaemic control; Type 2 diabetes.