Once-Weekly Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Common OAD: a Subgroup Analysis from SUSTAIN 2–4 and 10

• Published in: Diabetes therapy Vol. 11; no. 5; pp. 1061 - 1075
• Main Authors: Capehorn, Matthew, Ghani, Yasmin, Hindsberger, Charlotte, Johansen, Pierre, Jódar, Esteban
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.05.2020; Springer Nature B.V
• Subjects: Antidiabetics; Cardiology; Clinical trials; Diabetes; Drug dosages; Drug therapy; Endocrinology; Glucose; Hemoglobin; Hypoglycemia; Internal Medicine; Medicine; Medicine & Public Health; Original Research; Weight control; Diabetes care; Oral antidiabetic agents; Randomised controlled trials; Sulphonylurea; Type 2 diabetes; GLP-1RA; Semaglutide; Metformin
• ISSN: 1869-6953; 1869-6961
• DOI: 10.1007/s13300-020-00796-z

Introduction Despite treatment with oral antidiabetic drugs (OADs), achieving effective glycaemic control in type 2 diabetes (T2D) remains a challenge. The objective of this post hoc analysis of data from the SUSTAIN 2, 3, 4 and 10 active-controlled trials was to assess the efficacy and safety of the once-weekly glucagon-like peptide 1 receptor agonist (GLP-1RA) semaglutide in patients on background treatment with metformin (MET), with or without a sulphonylurea (SU). Methods Data from the randomised phase 3 trials SUSTAIN 2, 3, 4 and 10 for subjects who received background MET alone or MET + SU were analysed. Change from baseline in HbA 1c and body weight at the end of treatment visit (week 30 in SUSTAIN 4 and 10, week 56 in SUSTAIN 2 and 3), and rates of hypoglycaemia and adverse events leading to premature treatment discontinuation were assessed. Results In total, 3411 subjects were included in the full analysis set (3410 in the safety analysis set). Across the four trials, semaglutide significantly reduced HbA 1c (estimated treatment difference [ETD] − 0.32 to − 0.79%-points for semaglutide 0.5 mg, and − 0.38 to − 1.07%-points for semaglutide 1.0 mg vs comparators; p  < 0.01) in subjects receiving both MET and MET + SU. Regardless of background OAD, semaglutide significantly reduced body weight (ETD − 2.35 to − 4.72 kg for semaglutide 0.5 mg, and − 2.96 to − 6.76 kg for semaglutide 1.0 mg vs comparators; p  < 0.0001). Across the trials, hypoglycaemic events were more common with background MET + SU than MET alone, in subjects receiving either semaglutide or a comparator. The rate of adverse events (AEs) leading to premature treatment discontinuations in subjects treated with semaglutide were generally consistent regardless of background therapy. Conclusion Semaglutide 0.5 mg and 1.0 mg significantly improve glycaemic control (HbA 1c ) and body weight in subjects with T2D, with a similar tolerability profile, regardless of whether they receive background MET or MET + SU. Trial Registration Clinicaltrials.gov: NCT01930188 (SUSTAIN 2), NCT01885208 (SUSTAIN 3), NCT02128932 (SUSTAIN 4) and NCT03191396 (SUSTAIN 10).