The Association of Long‐acting Insulin Analogue Use Versus Neutral Protamine Hagedorn Insulin Use and the Risk of Major Adverse Cardiovascular Events among Individuals with Type 2 Diabetes: A Population‐based Cohort Study

Aims To compare the risk of cardiovascular outcomes associated with long-acting insulin analogues versus neutral protamine Hagedorn (NPH) insulin among patients with type 2 diabetes. Materials and Methods We conducted a population-based retrospective cohort study using the UK Clinical Practice Research Datalink Aurum, linked with hospitalization and vital statistics data. Patients with type 2 diabetes who initiated basal insulin treatment between 2002 and 2018 were included in the study. Exposure was defined as current use of long-acting insulin analogues or NPH insulin, defined using a time-varying approach. The primary outcome was major adverse cardiovascular events (MACE; a composite endpoint of myocardial infarction, ischaemic stroke and cardiovascular death). We used a marginal structural Cox proportional hazards model to estimate the hazard ratio (HR) and 95% confidence interval (CI) for MACE with current use of long-acting insulin analogues versus NPH insulin, and in secondary analyses, by long-acting insulin molecule. Results Our cohort included 57 334 patients. A total of 3494 MACE occurred over a mean follow-up of 1.6 years (incidence rate 37.4, 95% CI 36.2 to 38.7 per 1000 person-years). Long-acting insulin analogues were associated with a decreased risk of MACE compared to NPH insulin (HR 0.89, 95% CI 0.83 to 0.96). Conclusions Current use of long-acting insulin analogues is associated with a modestly reduced risk of MACE compared to current use of NPH insulin among patients with type 2 diabetes. This study could have important implications for drug plan managers and guideline-writing committees for recommendations of insulin treatment for type 2 diabetes.