Comparative vascular safety of basal long-acting insulin analogue versus intermediate-acting human insulin in real-world patients with type 2 diabetes: a nationwide population-based cohort study

Background: Little is known about the comparative vascular safety of basal insulin (intermediate-acting human insulin [IAHI] or long-acting insulin analogue [LAIA]) in type 2 diabetes. We sought to examine the vascular and hypoglycemic effects associated with IAHI versus LAIA in real-world patients with type 2 diabetes. Methods: We conducted a nationwide population-based, retrospective cohort study using Taiwan’s National Health Insurance Research Database to include patients with type 2 diabetes who stably used an 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 composite cardiovascular diseases (CVDs), composite microvascular diseases (MVDs), and hypoglycemia, were assessed up to the end of 2013. Results: Baseline patient characteristics were balanced with the application of the matching scheme. Compared with LAIA, the use of IAHI was associated with greater risks of composite CVDs (adjusted hazard ratio: 1,79; 95% confidence interval: 1.20-2.67) and hospitalized hypoglycemia (1.82; 1.51-2.20), but a lower risk of composite MVDs (0.88; 0.84-0.91). Subgroup and sensitivity analyses showed a consistent trend of results with that in the primary analyses. Conclusions: The use of a basal insulin with IAHI versus LAIA among patients with type 2 diabetes in usual practice may be associated with a lower risk of MVDs, and strategies should be optimized for minimizing the risks of hypoglycemia and CVDs in this population.