Real-World Effectiveness of Once-Weekly Semaglutide From a US Commercially Insured and Medicare Advantage Population.

PURPOSE: Patients managing type 2 diabetes mellitus (T2DM) often require combination therapy to meet their blood glucose control targets. With limited real-world evidence focused on the use of glucagon-like peptide 1 receptor agonist (GLP-1RA) therapies, the objective of this study was to describe the association between semaglutide once weekly (OW) initiation and changes in hemoglobin A (A) levels. METHODS: This retrospective, descriptive cohort study used the HealthCore Integrated Research Environment (HIRE) to examine commercially insured and Medicare Advantage patients who had T2DM while taking semaglutide OW from December 1, 2017, to April 30, 2019. The first semaglutide OW prescription fill was defined as the study index date. Changes in mean A levels and A target attainment were evaluated among an intention-to-treat (ITT) population (overall group). Furthermore, a persistent population (PP) analysis on the same outcomes was performed that was limited to ITT patients who were observed to continue to use semaglutide OW at the time of the postindex A measurement. In addition, these outcomes were explored in patients stratified based on prior use of GLP-1RA therapy (experienced vs naive) and baseline A values >9% (75 mmol/mol). FINDINGS: A total of 1888 patients were identified in the overall ITT group. The mean change in the overall ITT group between preindex and postindex A values was -0.9% percentage points (-9.8 mmol/mol) (mean preindex A, 8.2% [66.1 mmol/mol]) and -1.1 percentage points (-12.0 mmol/mol) (mean preindex A, 8.2% [66.1 mmol/mol]) in the PP subgroup (all P < 0.001). Among the subgroup of patients with a baseline A value >9% (75 mmol/mol), percentage point changes in A were -2.2 (-24.0 mmol/mol) and -2.4 (-26.2 mmol/mol) (all P < 0.001). When accounting for prior GLP-1RA use, the GLP-1RA-naive stratum had double the mean reduction in A compared with the GLP-1RA-experienced stratum (-1.2 [-13.1 mmol/mol] vs -0.6 [-6.6 mmol/mol] percentage points). IMPLICATIONS: Semaglutide OW is associated with clinically and statistically significant A reduction and increases in reaching A targets using real-world data, even in GLP-1RA-experienced patients, despite more frequent use of insulin or sodium glucose transport protein 2 inhibitors in this group. Target A attainment significantly increased overall and within all subgroups and strata, with approximately half of all patients attaining an A value <7% (53 mmol/mol) and three-quarters attaining an A value <8% (64 mmol/mol).