Real-World Evaluation of GLP-1 Receptor Agonist Therapy Persistence, Adherence and Therapeutic Inertia Among Obese Adults with Type 2 Diabetes

INTRODUCTION: In type 2 diabetes (T2D), key barriers to optimal glycaemic control include lack of persistence with treatment, reduced medication adherence and therapeutic inertia. This study aimed to assess the impact of these barriers in obese adults with type 2 diabetes treated with a GLP-1 receptor agonist (GLP-1RA) and compare them against other glucose-lowering agents in a real-world setting. METHODS: A retrospective study was conducted using electronic medical records from 2014 to 2019 for adults with T2D at the Valencia Clínico-Malvarrosa Department of Health (Valencia, Spain). Four study groups were established: all GLP-1RA users, SGLT2i users, insulin users and other glucose-lowering agent users (miscellany group). To account for imbalance between groups, propensity score matching (PSM) including age, gender and pre-existing cardiovascular disease was performed. Chi-square tests were used for comparisons between groups. Time to first intensification was calculated using competing risk analysis. RESULTS: Among the 26,944 adults with T2D, 7392 individuals were selected following PSM, with 1848 patients in each group. At 2 years, GLP-1RA users were less persistent than non-users (48.4% versus 72.7%, p < 0.0001) but more adherent (73.8% versus 68.9%, respectively, p < 0.0001). A greater proportion of persistent GLP-1RA users than non-persistent users exhibited reduced HbA1c (40.5% versus 18.6%, respectively, p < 0.0001), but no differences in cardiovascular outcomes and death were found. Overall, therapeutic inertia was observed in 38.0% of the study population. The large majority of GLP-1RA users received treatment intensification, whereas only 50.0% of GLP-1RA non-users were intensified. CONCLUSION: Under real-life conditions, obese adults with T2D persistently treated with GLP-1RA showed improved glycaemic control. Despite benefits, persistence with GLP-1RA was limited after 2 years. Additionally, therapeutic inertia occurred in two out of three study participants. Strategies to facilitate medication adherence, persistence and treatment intensification in people with T2D should be made a priority in order to achieve and maintain glycaemic targets and improve outcomes in this population. TRAIL REGISTRATION: Study registered in clinicaltrials.org with the identifier NCT05535322.