Does antihyperglycemic medication adherence reduce stroke hazard among Type 2 diabetes patients?

Background: Stroke is the third leading cause of mortality, affecting about 800.000 adults each year. Diabetes is a major stroke risk factor, and stroke mortality is doubled if diabetes is present. The empirical causal relationship between stroke and glycemic control remains speculative, although cross sectional and attributed associations are documented. We studied medication adherence vs. stroke risk using Taiwan's national, population-based, 10-year, longitudinal dataset from its single payer, nationwide universal coverage, single health plan system with comprehensive benefit package, low copayments and almost no access barriers. Significant stroke risk reduction findings can motivate diabetes patients for high adherence and motivate providers and health plans to aggressively pursue medication adherence among patients and dramatically reduce stroke morbidity, mortality and costs.

Objective: To examine whether adherence to antidiabetic medication confers protection from stroke among type 2 diabetes patients.

Methods: An all-medical care claims merged database of all Taiwanese patients with a diabetes diagnosis 2000-2009 was used. Newly diagnosed diabetes patients, diagnosed 2000-2008, followed up through 2009, 43,034 patients who suffered stroke 1+ years after diagnosis, and 173,468 matched controls (1:4) on month of diabetes diagnosis, age and gender, with at least one prescription filled for antihyperglycemic medication in the year prior to stroke/pseudo-event for matched controls. Adherence was measured as Proportion of Days Covered (PDC) by antihyperglycemic prescription refills in the year before stroke Time dependent proportional hazard regression was used to model stroke hazard using PDC (≥0.8, 0.4-0.79, <0.4) and Charlson Comorbidities (≤2, 3-5, 6+) as time dependent variables, adjusting for age, gender, Defined Daily Dose (DDD) for diabetes severity, hypertension, hyperlipidemia, urbanization, treating physician specialty and medical facility, and Diabetes Care Program participation. Results/ Conclusion: Stroke hazard ratio (annual exponential value) since diabetes diagnosis was 1.09 for PDC<0.4 and 1.05 for 0.4 < PDC < 0.8 vs. PDC 0.8, translating to hazard ratios of 2.31 and 1.61 respectively in Year 10. For Charlson Comorbidities, the corresponding ratios were 1.07 and 1.05 for >5 and 3-5 comorbidities vs. <2 group respectively, translating to 1.42 and 1.24 in Year 10. Participation in diabetes care program cut stroke risk in half. Antidiabetic medication adherence yields rich stroke reduction benefits, cutting stroke risk several-fold when cumulative hazard in all years is considered. Protection from medication adherence and diabetes care program participation exceed the risk from factors beyond patient control, namely co-morbidities. This study provides the first ever empirical evidence of long-term stroke protection from antihyperglycemic medication adherence.