All-Cause and Cause-Specific Mortality among Users of Basal Insulins NPH, Detemir, and Glargine

PLoS One. 2016 Mar 31;11(3):e0151910. doi: 10.1371/journal.pone.0151910. eCollection 2016.

Abstract

Background: Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown.

Objective: To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland.

Methods: 23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006-2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years).

Results: 2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30-0.50) for detemir, and 0.55 (95% CI, 0.44-0.69) for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54-0.93) among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses.

Conclusion: In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / mortality
  • Cause of Death
  • Cohort Studies
  • Databases, Factual
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Finland
  • Gastrointestinal Diseases / epidemiology
  • Gastrointestinal Diseases / mortality
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Glargine / therapeutic use*
  • Insulin, Isophane / therapeutic use*
  • Insulin, Long-Acting / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasms / epidemiology
  • Neoplasms / mortality
  • Risk

Substances

  • Hypoglycemic Agents
  • Insulin, Long-Acting
  • Insulin Glargine
  • Insulin, Isophane

Grants and funding

Retrieval of national register data by EPID Research was financially supported by Novo Nordisk Pharma. AYS’s research is supported by the Gustaf V and Queen Victoria Frimurarestiftelse. FH, SC, JH and PK are employed by EPID Research and received funding in the form of salaries. The specific roles of these authors are articulated in the 'Author Contributions' section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.