Once-Weekly Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Common OAD: a Subgroup Analysis from SUSTAIN 2–4 and 10

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). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-020-00796-z) contains supplementary material, which is available to authorized users.