Real-World Effectiveness and Safety of Escalating Once-Weekly Semaglutide from 0.5 to 1.0 mg in Type 2 Diabetes.

INTRODUCTION: Real-world data on escalation of once-weekly semaglutide from 0.5 to 1.0 mg remain limited. Therefore, we aimed to evaluate the effectiveness and safety of this dose escalation in routine clinical practice. METHODS: This was a single-center, retrospective cohort study involving adults with type 2 diabetes who received an escalated once-weekly semaglutide dose from 0.5 to 1.0 mg in routine clinical care. The primary outcome was within-patient change in glycated hemoglobin (HbA1c) level 24 weeks after the initial prescription of 1-mg semaglutide. Secondary outcomes included changes in metabolic parameters and the incidence of newly documented adverse events after escalation to 1.0 mg. Efficacy was analyzed in a prespecified on-treatment set, and safety was assessed in an all-exposed set. RESULTS: In the efficacy set (n = 126), the HbA1c level decreased by 0.40% ± 0.70% and body weight by 2.2 ± 2.7 kg at week 24 (both p < 0.01). Additionally, reductions were observed in alanine aminotransferase and γ-glutamyl transpeptidase levels, total number of concomitant glucose-lowering agents, and total daily insulin dose. In the safety set (n = 128), gastrointestinal adverse events were the most frequent (20.3%), particularly nausea (14.1%). Dose reduction was required in 12.5% of patients, mostly owing to gastrointestinal symptoms, and discontinuation for any reason occurred in 5.5%; only one patient (0.8%) discontinued treatment because of an adverse event. No serious drug-related adverse events were recorded. CONCLUSIONS: In this real-world cohort, escalation of once-weekly semaglutide dose to 1.0 mg was associated with additional reductions in HbA1c level and body weight, without serious adverse events. Although causal incremental benefit cannot be established because of the single-arm design without a 0.5-mg maintenance comparator, these findings may support clinical decision-making regarding dose intensification in patients experiencing suboptimal control with 0.5-mg semaglutide. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000059813, retrospectively registered on November 18, 2025.