Clinical characteristics associated with adherence and persistence in patients with type 2 diabetes mellitus treated with dulaglutide

Abstract

Dulaglutide is a Glucagon-like Peptide-1 Receptor Agonist (GLP-1RA) indicated for the treatment of type 2 diabetes mellitus (T2DM). However, as an injectable therapy, treatment with dulaglutide has been complicated by suboptimal adherence and persistence rates. The objective of this study was to identify clinical characteristics associated with adherence and persistence in T2DM patients treated with dulaglutide. This retrospective observational cohort study used electronic medical records transformed into the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM, version 5.3.1) of Seoul National University Hospital (SNUH), Seoul, South Korea. Patients with T2DM who initiated treatment with dulaglutide (0.75 mg or 1.5 mg) between January 1st, 2018 and December 31st, 2019 were included and followed for one year since treatment initiation. Adherence was evaluated by using proportion of days covered (PDC) and adherence status (PDC≥0.8 or PDC<0.8). Persistence was assessed with treatment duration (the number of days on treatment without >60 days prescription gap) and continuation status (continuer or discontinuer). Multivariate linear regression and multivariate logistic regression were used to identify the factors associated with continuous and categorical outcome measures, respectively. Subgroup analysis was conducted involving patients with high cardiovascular disease (CVD) risk (i.e., having ≥2 identifiable risk factors for cardiovascular disease). Sensitivity analysis was conducted by 1) changing the permissible prescription gap for continuous treatment to >90 days and 2) defining subjects with high CVD risk as having ≥3 identifiable CVD risk factors. A total of 236 patients met the eligibility criteria and were included in the analyses. In multivariate logistic regression analyses, a year increase in age and a unit increase in estimated glomerular filtration rate significantly increased the likelihood of adherence and treatment continuation. In contrast, patients with baseline obesity and baseline use of sulfonylurea and insulin were significantly less likely to continue treatment with dulaglutide. In multivariate linear regression analyses, a year increase in age, switching dulaglutide dose, and baseline neuropathy were significantly associated with higher PDC and longer treatment duration, while baseline use of insulin and sulfonylurea were associated with lower PDC and shorter treatment duration. In subgroup analysis, there was no significant differences in dulaglutide adherence and persistence between patients with high CVD risk and those with low CVD risk. Sensitivity analyses showed no statistically significant difference in the adherence and persistence results. This study found clinical characteristics of dulaglutide users who are more likely to be adherent and persistent to dulaglutide. It is expected that the findings of this study can be used in guiding prescriptions for T2DM patients considering to initiate treatment with dulaglutide.

Dulaglutide는 Glucagon-like Peptide 1 수용체 작용체(GLP-1RA) 계열의 제2형 당뇨병(T2DM) 치료제다. 그러나 Dulaglutide는 주사제로 사용되기 때문에 치료 순응도와 지속도가 낮다. 본 연구는 대한민국에서 Dulaglutide로 치료받는 제2형 당뇨병 환자의 순응도 및 지속도에 영향을 미치는 임상적 특징을 분석했다. 본 연구는 후향적 코호트 연구로 서울대학교병원(SNUH)의 Observational Medical Outcomes Partnership Common Data Model(OMOP CDM, 버전 5.3.1)로 변환된 전자 의무 기록을 사용했다. 2018년 1월 1일부터 2019년 12월 31일 사이에 Dulaglutide(0.75mg 또는 1.5mg)로 치료를 시작한 제2형 당뇨병 환자의 치료 시작 후 1년간 기록된 정보를 분석에 사용했다. 순응도는 proportion of days covered(PDC)와 adherence status(PDC≥0.8 또는 PDC<0.8)를 사용해 평가했다. 지속도는 60일을 초과하는 처방 공백 없이 지속적으로 치료받은 기간과 치료 중단 여부로 평가했다. 다변량 선형 회귀 및 다변량 로지스틱 회귀 분석을 사용해 연속 및 범주형 결과변수에 영향을 주는 요인을 분석했다. 또한 2 가지 이상의 심혈관질환(Cardiovascular disease, CVD) 위험 인자를 가진 환자를 대상으로 하위집단 분석을 수행했다. 마지막으로 민감도분석을 통해 결과의 강건성(robustness)을 평가했다. 총 236명의 환자가 분석에 포함됐다. 다변량 로지스틱 회귀분석 결과 연령 및 사구체 여과율이 높을수록 순응도 및 치료 지속도가 유의하게 증가했다. 반면 비만이 있거나 설포닐유레아 및 인슐린을 사용하는 환자는 치료 지속 가능성이 낮았다. 다변량 선형 회귀분석 결과, 연령 및 용량 변경, 신경병증이 PDC와 치료 기간을 유의하게 증가시켰다. 심혈관질환 고위험군을 대상으로 실시한 하위집단 분석 결과 심혈관질환 위험도는 Dulaglutide 순응도와 지속도에 통계적으로 유의한 영향을 주지 않았다. 본 연구 결과가 Dulaglutide로 치료받는 제2형 당뇨병 환자의 순응도 및 지속도를 향상시키고 궁극적으로 치료효과를 높이는데 활용되길 기대한다.