A nationwide cohort study for comparative vascular safety of long-acting insulin analogue versus intermediate-acting human insulin in type 2 diabetes

Little is known about the comparative vascular safety of basal insulins (intermediate-acting human insulin [IAHI] or long-acting insulin analogue [LAIA]) in type 2 diabetes (T2D). This study sought to examine the vascular and hypoglycemic effects associated with IAHI versus LAIA in real-world patients with T2D. We utilized Taiwan’s National Health Insurance Research Database to identify T2D patients who stably used IAHI (N = 11,521) or LAIA (N = 37,651) in the period 2004–2012. A rigorous three-step matching algorithm that considered the initiation date of basal insulin, previous exposure of antidiabetic treatments, comorbidities, diabetes severity and complications, and concomitant medications was applied to achieve the between-group comparability. Study outcomes, including cardiovascular diseases (CVDs), microvascular diseases (MVDs), and hypoglycemia, were assessed up to the end of 2013. Compared with LAIA, the use of IAHI was associated with greater risks of composite CVDs (adjusted hazard ratio [aHR]: 1.79; 95% confidence interval [CI] 1.20–2.67) and hospitalized hypoglycemia (aHR: 1.82; 95% CI 1.51–2.20), but a lower risk of composite MVDs (aHR: 0.88; 95% CI 0.84–0.91). Subgroup and sensitivity analyses showed a consistent trend of results with that in the primary analyses. In summary, although the use of IAHI versus LAIA among T2D patients in usual practice may be associated with a lower risk of MVDs, strategies should be optimized for minimizing the risks of hypoglycemia and CVDs in this population.