Gradual Titration of Semaglutide Results in Better Treatment Adherence and Fewer Adverse Events: A Randomized Controlled Open-Label Pilot Study Examining a 16-Week Flexible Titration Regimen Versus Label-Recommended 8-Week Semaglutide Titration Regimen

OBJECTIVE To determine whether a slower, flexible titration regimen of semaglutide would improve adherence and reduce gastrointestinal adverse events (GI-AEs) compared with the label-recommended regimen in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS A total of 104 patients with T2D were randomized to label-recommended titration (0.25 mg, 0.5 mg, 1 mg at 4-week intervals) or flexible titration (starting at 0.0675 mg [measured as five clicks made by the dose selector dial], with gradual increases by 0.0675 mg/week and delays for GI-AEs) for 26 weeks. RESULTS While final doses were similar between groups, only 2% of patients in the flexible arm withdrew due to GI-AEs vs. 19% in the label arm (P = 0.005). The flexible arm reported less nausea (45.1% vs. 64.2%; P = 0.051) and asthenia (9.8% vs. 24.5%; P = 0.047), with fewer days experiencing nausea (2.88 vs. 6.3 days; P = 0.017). HbA_1c and BMI changes were similar between groups. CONCLUSIONS Slower, flexible titration improved adherence and reduced adverse events without compromising efficacy.