Impact of baseline characteristics and beta-cell function on the efficacy and safety of subcutaneous once-weekly semaglutide: A patient-level, pooled analysis of the SUSTAIN 1-5 trials.

ABSTRACT

AIM: To evaluate the impact of relevant patient-level characteristics on the efficacy and safety of subcutaneous, once-weekly semaglutide in subjects with type 2 diabetes. MATERIALS AND METHODS: Exploratory post hoc analyses of pooled SUSTAIN 1-5 (phase 3a) randomized, controlled trials examined the change from baseline in HbA1c and body weight (BW), and the proportions of subjects achieving the composite endpoint (HbA1c < 7.0% [53 mmol/mol]), without weight gain or severe/blood glucose-confirmed symptomatic hypoglycaemia at week 30 with semaglutide (0.5/1.0 mg) across clinically relevant patient subgroups baseline HbA1c (≤7.5%, >7.5%-8.0%, >8.0%-8.5%, >8.5%-9.0% and > 9.0%), background medications, diabetes duration and pancreatic beta-cell function. RESULTS: Mean HbA1c (% point) reductions increased from lowest to highest HbA1c subgroups (-0.9%, -1.2%,-1.5%, -1.7% and -2.3% [effect of subgroup within treatment P = 0.247] for semaglutide 0.5 mg, and -1.1%, -1.4%, -1.9%, -2.1% and -2.7% [P = 0.045] for semaglutide 1.0 mg), with mean HbA1c ranges at week 30 of 6.3%-7.3% and 6.1%-6.9%, respectively. The corresponding BW reductions generally decreased with increasing baseline HbA1c (-4.4, -3.9, -3.9, -3.3 and -2.9 kg [P = 0.004], and -6.4, -5.9, -5.2, -4.5 and -4.8 kg [P < 0.001], respectively). HbA1c and BW reductions were consistently greater for semaglutide 1.0 mg versus 0.5 mg across background medication, diabetes duration and pancreatic beta-cell function subgroups. Adverse events with semaglutide were consistent with the glucagon-like peptide-1 receptor agonist class, with gastrointestinal events the most common. CONCLUSIONS: Semaglutide was consistently efficacious across the continuum of diabetes care in a broad spectrum of patient subgroups with a range of clinical characteristics.