Real-world persistence and dose titration of GLP-1 receptor agonists in type 2 diabetes: A UK population-based cohort study by obesity and cardiovascular disease status.

AIMS: Real-world medication use varies across clinical trial and healthcare settings; therefore, we evaluated GLP-1 receptor agonist (GLP-1RA) persistence and dose titration among adults with type 2 diabetes in UK primary care, stratified by agent, obesity status, cardiovascular disease (CVD) history, and sex assigned at birth. MATERIALS AND METHODS: Adults with type 2 diabetes initiating GLP-1RAs between 1 March 2018 and 30 June 2023, with follow-up ≥1-year, were identified using the IQVIA Medical Research Data (IMRD) incorporating data from THIN, A Cegedim Database. The absolute 1-year risk of discontinuation was estimated using the Aalen-Johansen estimator, while multivariable cause-specific Cox models assessed associations with patient characteristics. Dosing trajectories were characterised across individual prescriptions during the first therapy year. RESULTS: Among 8200 GLP-1RA initiators (46.5% dulaglutide, 38.7% semaglutide), the 1-year discontinuation risk was 41.1% (95% CI 40.1-42.2), higher among those without obesity (BMI <30 kg/m: 49.2%, 46.5-52.0) versus with BMI ≥30 kg/m(BMI 30-<35/≥35 kg/m: 40.4%/37.2%, 38.4-42.4/35.4-39.1). Discontinuation was lower with dulaglutide (36.9%, 35.4-38.4) than with subcutaneous/oral semaglutide (46.4%/55.8%, 44.4-48.4/52.3-59.4). Only 58% of subcutaneous/oral semaglutide initiators reached recommended maintenance doses after 4 weeks, while 21% remained on starting doses. At prescription 10, most common doses were 0.5/1 mg subcutaneous semaglutide (44.0%/48.6%), 7/14 mg oral semaglutide (50.2%/36.6%), and 0.75/1.5/3 mg dulaglutide (20.4%/71.5%/6.7%). Faster dose escalation occurred with higher BMI and subcutaneous semaglutide (1 mg at prescription 5: 20.8%/25.9%/33.2% with BMI <30/30-<35/≥35 kg/m). Additional analyses (e.g., by CVD history) revealed no further heterogeneity. CONCLUSIONS: In UK primary care, GLP-1RA persistence was suboptimal and dose escalation was frequently delayed across all patient stratifications, including individuals with established CVD.