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

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_1c (A_1c) levels.

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_1c levels and A_1c 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_1c measurement. In addition, these outcomes were explored in patients stratified based on prior use of GLP-1RA therapy (experienced vs naive) and baseline A_1c values >9% (75 mmol/mol).

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_1c values was -0.9% percentage points (-9.8 mmol/mol) (mean preindex A_1c, 8.2% [66.1 mmol/mol]) and -1.1 percentage points (-12.0 mmol/mol) (mean preindex A_1c, 8.2% [66.1 mmol/mol]) in the PP subgroup (all P < 0.001). Among the subgroup of patients with a baseline A_1c value >9% (75 mmol/mol), percentage point changes in A_1c 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_1c compared with the GLP-1RA-experienced stratum (-1.2 [-13.1 mmol/mol] vs -0.6 [-6.6 mmol/mol] percentage points).

Semaglutide OW is associated with clinically and statistically significant A_1C reduction and increases in reaching A₁ 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_1c attainment significantly increased overall and within all subgroups and strata, with approximately half of all patients attaining an A_1c value <7% (53 mmol/mol) and three-quarters attaining an A_1c value <8% (64 mmol/mol).