Semaglutide Once-Weekly Persistence and Adherence Versus Other GLP-1 RAs in Patients with Type 2 Diabetes in a US Real-World Setting

Abstract

Introduction: The superior efficacy and safety of semaglutide once-weekly (QW), compared with dulaglutide, liraglutide, or exenatide QW, have been demonstrated in the SUSTAIN trials. This study assessed treatment persistence and adherence to semaglutide QW versus dulaglutide, liraglutide, or exenatide QW in a realworld setting. Methods: This retrospective, database study used Optum's de-identified ClinformaticsÒ Data Mart Database to identify glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment-naïve adult patients with type 2 diabetes (T2D) initiating semaglutide QW, dulaglutide, liraglutide, or exenatide QW between January 1, 2018 and April 30, 2019. Persistence (time remaining on treatment) was assessed with Kaplan-Meier survival estimates and Cox proportional hazard models. Adherence was assessed using proportion of days covered (PDC) and proportion of patients with PDC [ 80%. Results: Of 56,715 patients included, 3279 received semaglutide QW, 27,891 dulaglutide, 17,186 liraglutide, and 8359 exenatide QW. Patients initiating semaglutide QW were younger and with lower percentage of Medicare coverage than patients initiating the comparators. Persistence at 360 days was significantly higher for semaglutide QW (67.0%) versus dulaglutide (56.0%), liraglutide (40.4%), and exenatide QW (35.5%); p \ 0.001 for all comparisons. Compared with semaglutide QW, the discontinuation rate was significantly higher for dulaglutide (hazard ratio [HR] 1.22; 95% confidence interval [CI] 1.13, 1.32; p \ 0.001), liraglutide (HR 1.80; 95% CI 1.66, 1.95; p \ 0.001), and exenatide QW (HR 2.12; 95% CI 1.96, 2.30; p \ 0.001). Adherence to semaglutide QW versus liraglutide at 360 days and to exenatide QW was 39.1% versus 30.0% [p = 0.07] and 27.7% [p = 0.02], respectively. Adherence to dulaglutide at 360 days was numerically higher than semaglutide QW (43.2% versus 39.1%; p = 0.45) but did not reach statistical significance. Conclusion: Persistence with semaglutide QW was significantly greater than comparators, while adherence was comparable or greater. Together with earlier results from double-blind clinical studies, these data support semaglutide QW use for treatment of patients with T2D.

Effectiveness in Real World of Once Weekly Semaglutide in People with Type 2 Diabetes: Glucagon-Like Peptide Receptor Agonist Naïve or Switchers from Other Glucagon-Like Peptide Receptor Agonists: Results from a Retrospective Observational Study in Umbria

“…In addition, data from the US Commercially Insured and Medicare Advantage Population ( N = 1888) showed that naïve patients obtained a reduction in HbA1c two times larger than that of switchers (− 1.2% vs. 0.6%); additionally, among the subgroup of patients with a baseline HbA1c value > 9% (75 mmol/mol), percentage point changes in HbA1c were − 2.2% (− 24.0 mmol/mol) [ 27 ]. Another US retrospective study using Optum's de-identified Clinformatics® Data Mart Database assessed that persistence at 360 days was significantly greater with semaglutide (67%) than for comparators (dulaglutide 56%, liraglutide 40%, and exenatide QW 35.5%), while adherence was comparable or greater [ 28 ].…”

Adherence and persistence rates of major antidiabetic medications: a review

“…The average PDC of injectable GLP-1RA agents at six months ranged from 0.61 to 0.76 [ 71 , 72 ]. The proportion of patients who continued treatment with injectable GLP-1RA at six months was between 32.1 and 74.0% [ 73 , 74 ]. The adherence and persistence of oral semaglutide remain to be seen.…”

“…In general, GLP-1RA agents with QW regimen demonstrated significantly better adherence and persistence than GLP-1RA agents with QD or BID regimen [ 67 , 72 , 74 , 76 ]. In terms of delivery method, GLP-1RA agents using simple delivery systems (single-use pen or auto-injector device) had significantly higher adherence and persistence than GLP-1RA using multi-use pen or syringe [ 67 , 71 , 75 – 77 ].…”

“…42% had at least one gap of > 30-day prescription gap. 22% discontinued after the first prescription gap Glucagon-like peptide-1 receptor agonists Mody et al, 2021 [ 75 ] HealthCore Integrated Research Database (HIRD) Proportion of days covered (PDC) The number of days of continuous treatment without a gap in therapy of greater than 45 days 18,650 T2DM patients aged 18 or older who initiated one of the index medications between February 2018 and December 2018; matched cohorts through propensity score matching, consisting of 12,919 patients on dulaglutide, 3,852 patients on semaglutide, and 1,879 on exenatide BCise 6 months Dulaglutide users had significantly higher mean PDC (0.75 vs. 0.67, p < 0.0001) and proportion of persistent patients (69.2% vs. 59.2%, p < 0.0001) compared with semaglutide users; dulaglutide users had significantly higher mean PDC (0.75 vs. 0.63, p < 0.0001) and proportion of persistent patients (67.9% vs. 50.6%, p < 0.0001) compared with exenatide BCise users Tofe et al, 2021 [ 77 ] Hospital recrods at Son Espases University Hospital, Palma de Mallorca, Spain Days covered by medication fills as measured by quarterly evaluation of pharmacy claims Discontinuation rates registered in patients' records at each visit during the follow-up period 298 T2DM patients aged 18 or older who initiated dulaglutide or sc semaglutide between January 2019 and June 2020; matched cohorts through propensity score matching consisting of 183 patients on dulaglutide and 115 patients on sc semaglutide 6 months 84.25% of dulaglutide users were adherent at 6 months; 83.71% of sc semaglutide users were adherent at 6 months; 20.5% of dulaglutide users discontinued at 6 months; 21.4% of sc semaglutide users discontinued at 6 months Mody et al, 2018 [ 71 ] HealthCore Integrated Research Database (HIRD) Proportion of days covered (PDC) The number of days of continuous treatment without a gap in therapy of greater than 45 days 1,970 T2DM patients aged 18 or older with at least one pharmacy claim for dulaglutide between November 1, 2014 and November 30, 2015 183 days 61% of patients were adherent (PDC ≥ 0.8); the mean PDC was 0.76; 37% patients discontinued; the mean number of days of persistent use of dulaglutide was 152 days Uzoigwe et al, 2021 [ 74 ] The Optum Clinformatics® Data Mart …”

Understanding the restrictions in the prescription and use of potentially beneficial diabetes medications associated with low socio-economic status

“…In addition, differences in income may not only be associated with disparities in the initiation of potentially beneficial medications, but also in adherence (regularly taking the medication at the dose and frequency as prescribed) and persistence (continuing treatment by refilling prescriptions as long as medically indicated). 10 Thus, the study by Falkentoft et al 5 leaves some important questions to be answered in the future.…”