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

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2022-11, Vol.24 (11), p.2169-2181
• Main Authors: Brunetti, Vanessa C., Yu, Oriana Hoi Yun, Platt, Robert W., Filion, Kristian B.
• Format: Article
• Language: English
• Subjects: Cardiovascular diseases; Cerebral infarction; Cohort analysis; cohort study; Diabetes; Diabetes mellitus (non-insulin dependent); Insulin; insulin analogues; Ischemia; Myocardial infarction; Patients; pharmaco‐epidemiology; Population studies; Population-based studies; Protamine; Protamine sulfate; type 2 diabetes
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.14802

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.