Évaluation de l’adhésion et de la persistance aux antidiabétiques, et de l’effet de la non-adhésion à la metformine sur la mortalité de toutes causes, sur l’utilisation et les coûts directs des soins de santé

Introduction: Optimal drug therapy in type 2 diabetes is critical, given the rising prevalence of diabetes, the impact of diabetes complications on the individual patient and its considerable public health burden. In this regard, three studies were designed 1) to estimate persistence rate, re-initiation rate after discontinuation, and adherence level among incident users of antidiabetics, and to investigate predictors of non-persistence and non-adherence; 2) to investigate the relationship between adherence level to metformin therapy and all-cause mortality over 10 years in incident metformin users; and 3) to describe healthcare utilization and direct costs over the 3 years following initiation of metformin therapy, and explore whether they differ according to the level of adherence to metformin therapy. Materials and Methods: A cohort of patients aged 45–85 years who initiated an antidiabetic in 2000- 2009, was extracted from the Quebec healthcare insurance databases. Persistence rate, re-initiation after discontinuation, and adherence level were assessed for all antidiabetic classes over 2 years. Then, a nested case-control study was conducted among patients initiating metformin therapy to investigate the relationship between adherence level and all-cause mortality. At last, healthcare utilization and direct costs were assessed over 3 years for all-cause hospitalizations, emergency department (ED) visits, and outpatient visits among patients initiating metformin therapy. For all three studies, adherence was assessed using the ‘medication possession ratio’ (MPR) over the follow-up duration. Patients with MPR ≥ 80% were deemed ‘adherent.’ Results: Inadequate use of antidiabetics in real-life settings is frequent among 160,231 incident metformin users. One year after antidiabetic initiation, persistence rate was 51% and adherence level 67%. Among those deemed non-persistent, 81% re-initiated antidiabetic therapy within 12 months of discontinuation. Moreover, the likelihood for non-persistence and non-adherence fluctuates according to antidiabetic class, economic status, comorbidities and comedications. Besides, investigating effectiveness in real-life of metformin therapy revealed decreased mortality risks after long-term adherence to metformin among 82,720 incident metformin users. Specifically, Rate Ratios were 0.84 [95% confidence intervals: 0.71- 0.98] and 0.69 [0.57-0.85] after 4 to 6 and ≥ 6 years of being adherent to metformin, respectively. Survival benefits were observed across all subgroups, and most particularly in patients using neither antihypertensive/cardiovascular drugs nor statins. Lastly, healthcare utilization and direct costs over the first years following initiation of metformin were substantial, and exploratory analyses suggested that individuals who were adherent had lower healthcare utilization and costs. Conclusions: Using a large population-based cohort, estimating medication usage in a real-life context highlights that inadequate treatment adherence is common among new antidiabetic users. Besides, longterm adherence to metformin (≥ 4 years) is associated with better survival in incident metformin users. Our findings emphasize the importance of conducting research aiming to improve long-term adherence to antidiabetics.

Keyphrases: observance, Antidiabetic, Hypoglycemic agents, Metformin, Adherence, Compliance, Persistence, All-cause mortality, Cost, Healthcare utilization