Effect of different methods for estimating persistence and adherence to new glucose-lowering drugs: results of an observational, inception cohort study in Portugal

Abstract

Purpose

Several methods have been developed for assessing medication-taking behavior; understanding the determinants and variability in estimates obtained is crucial in interpreting results. We estimated persistence and adherence levels to new glucose-lowering drugs (GLDs) in type 2 diabetes mellitus (T2DM) patients using different methods: through the collection of pharmacy records and combining pharmacy records with self-reported data.

Methods

We conducted a prospective observational cohort study of T2DM patients initiating a new GLD. Data were collected at baseline through interviews (demographic and clinical data). Follow-up data included pharmacy records (refill dates and medication possession) and telephone questionnaires (self-declared monitored GLD refill in another pharmacy, reasons for drug withdrawal). The cohort was divided into incident and prevalent new users. Persistence and adherence (proportion of days covered) were estimated for patients using pharmacy records exclusively (Method 1) and ≥1 self-declared statement of being persistent (Method 2). Log-rank tests were used to compare Kaplan–Meier curves of time to nonpersistence.

Results

A total of 1,328 patients were recruited. When considering Method 1, 38.7% (95% confidence interval [95% CI]: 36.0–41.5) of patients were persistent, whereas combining with self-reported information, this estimate increased to 65.6% (95% CI: 62.9–68.2). Using Method 1, the risk of persistence failure was associated with using an oral GLD, living alone and living in a suburban/urban setting. Three hundred and twenty-seven (24.8%) patients stopped to use the inception GLD.

Conclusion

Regardless of the method used, results indicated low levels of persistence and adherence to a new GLD; however, when combining self-reported information, higher estimates were obtained. Considering pharmacy records exclusively, prevalent new users, who were more complex patients in terms of T2DM disease but more likely to be pharmacy-loyal patients, were significantly more adherent than the incident new users. Barriers and reasons leading to GLD withdrawal, namely adverse drug event management, should be addressed, since they represent half of the reasons for treatment switching or discontinuation.

Keywords:

• type 2 diabetes mellitus
• medication use behavior
• discontinuation
• daily practice

Supplementary material

Figure S1 Study flow diagram.

Notes: Patients were allowed to fill in a questionnaire even if they had not completed the previous one. Among the eligible patients (1,328), 63.86% (n=848) started one DPP-4 alone or in fixed-dose combination with metformin, 11.07% (n=147) one GLP-1 and 23.19% (n=308) dapagliflozin. For 25 participants, two different inception GLDs were prescribed simultaneously (17 out of 25 started dapagliflozin with DPP-4 [alone or in fixed-dose combination with metformin]); these patients could stop the inception GLD in different moments. A total of 328 inception-monitored GLDs were stopped (24.4% [n=207] DPP-4 alone or in fixed-dose combination with metformin, 28.9% [n=89] dapagliflozin and 21.8% [n=32] GLP-1).

Abbreviations: DPP-4, dipeptidyl peptidase-4 inhibitor; GLD, glucose-lowering drug; GLP-1, glucagon-like peptide-1; INU, incident new user; PNU, prevalent new user.

Acknowledgments

The authors acknowledge all the community pharmacists and patients who voluntarily agreed to participate in this study.

Author contributions

CT was responsible for the implementation of the study, data analysis and drafting the manuscript. APM and HL had the original idea for the manuscript; they conducted and supervised the study and helped drafting the manuscript. JG and PL participated in data collection, analysis and revision of the manuscript. JFR participated in the collection of additional literature, contributed to the writing of the manuscript and revised it critically for important intellectual content. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work. All authors read and approved the final manuscript.

Disclosure

CT was working at CEFAR/National Association of Pharmacies (ANF) when the study was performed and is currently employed by the Portuguese Pharmaceutical Society and has no conflict of interest to declare. JFR has received honoraria for consultancy or giving lectures from Merck Sharp & Dohme, Lilly and Novo Nordisk over the last year. All costs associated with the development and implementation of this study were fully supported by the Portuguese ANF. ANF had no role in study protocol, data analysis or interpretation of this study. The authors report no other conflicts of interest in this work.