Long-term adherence to glucose-lowering therapy and cardiovascular risk in type 2 diabetes: a nationwide cohort study
Summary Background Type 2 diabetes is a major risk factor for cardiovascular disease, and reducing this excess risk is a central goal of clinical management. Sustained adherence to glucose-lowering medication is considered a key component of this strategy. However, long-term patterns of medication-taking behavior in real-world settings, and their relationship with cardiovascular outcomes, remain insufficiently characterized. Methods We conducted a nationwide cohort study of Danish adults with newly diagnosed type 2 diabetes who initiated non-insulin glucose-lowering medication between 2005 and 2012. Medication adherence was estimated from pharmacy dispensing data, and group-based trajectory modeling was used to identify longitudinal adherence patterns. The primary outcome was a composite cardiovascular outcome including ischemic heart disease, stroke, or heart failure. Associations between adherence trajectories and cardiovascular outcomes over 10 years of follow-up were assessed with Cox proportional-hazards models. Findings Among 79,510 individuals with newly diagnosed type 2 diabetes (median age, 61 (IQR: 52–69); 57% men), we identified three long-term adherence trajectories defined by high (n = 32,912; 41%), intermediate (n = 25,822; 33%), and low (n = 20,776; 26%) adherence. During follow-up, 15,276 cardiovascular events occurred. Compared with the high-adherence group, adjusted hazard ratios for the composite cardiovascular outcome were 1.07 (95% CI, 1.03–1.12) and 1.27 (95% CI, 1.21–1.33) in the intermediate- and low-adherence groups, respectively. Participants with high adherence remained free of cardiovascular events for an average of 220 more days (95% CI, 204–237) over 10 years. Associations were largely driven by ischemic heart disease, with no significant associations for heart failure. Interpretation Long-term adherence to glucose-lowering medication was associated with lower cardiovascular rate and longer event-free survival time among individuals with newly diagnosed type 2 diabetes. Funding Novo Nordisk Foundation and the European Innovation Council.