Electronic Medical Record Cancer Incidence over Six Years Comparing New Users of Glargine with New Users of NPH Insulin

Background: Recent studies suggested that insulin glargine use could be associated with increased risk of cancer. We compared the incidence of cancer in new users of glargine versus new users of NPH in a longitudinal clinical cohort with diabetes for up to 6 years. Methods and Findings: From all patients who had been regularly followed at Massachusetts General Hospital from 1/01/2005 to 12/31/2010, 3,680 patients who had a medication record for glargine or NPH usage were obtained from the electronic medical record (EMR). From those we selected 539 new glargine users (age: 60.1±13.6 years, BMI: 32.7±7.5 kg/m2) and 343 new NPH users (61.5±14.1 years, 32.7±8.3 kg/m2) who had no prevalent cancer during 19 months prior to glargine or NPH initiation. All incident cancer cases were ascertained from the EMR requiring at least 2 ICD-9 codes within a 2 month period. Insulin exposure time and cumulative dose were validated. The statistical analysis compared the rates of cancer in new glargine vs. new NPH users while on treatment, adjusted for the propensity to receive one or the other insulin. There were 26 and 28 new cancer cases in new glargine and new NPH users for 1559 and 1126 person-years follow-up, respectively. There were no differences in the propensity-adjusted clinical characteristics between groups. The adjusted hazard ratio for the cancer incidence comparing glargine vs. NPH use was 0.65 (95% CI: 0.36–1.19). Conclusions: Insulin glargine is not associated with development of cancers when compared with NPH in this longitudinal and carefully retrieved EMR data

Baseline unadjusted and propensity score weighted characteristics of new glargine and NPH insulin users.

<p>Note: Only patients with nonmissing values for all covariates are included. All variables were included in the logistic regression for propensity score.</p><p>Baseline unadjusted and propensity score weighted characteristics of new glargine and NPH insulin users.</p

Comparison of cancer incidence between new glargine and NPH users (Intent-to-Treat Analysis).

<p>CI, confidence interval; HR, hazard ratio. Note: Unadjusted HR and 95% CI were obtained from a Cox proportional hazards model adjusting for treatment only. Adjusted HR and 95% CI were obtained from a Cox proportional hazards model that adjusted for all variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109433#pone-0109433-t001" target="_blank">table 1</a> using inverse probability of treatment weights. Patients were followed until the first occurrence of one of the following events: the patient developed cancer, death, the study ended, or one year after the patient’s last visit in the database.</p><p>Comparison of cancer incidence between new glargine and NPH users (Intent-to-Treat Analysis).</p

Cancer free survival curves in new glargine and NPH insulin users.

<p>Cancer free survival curves in new glargine and NPH insulin users.</p

Association between long-acting insulin use and cancer for new users by dose category (As-Treated Analysis).

<p>Hazard ratios and their 95% CIs were obtained from Cox proportional hazards models adjusted for gender and age at the start of the dose category.</p><p>CI, confidence interval; HR, hazard ratio; IR, incidence rate per 100 person-years.</p><p>Patients were followed until the first occurrence of one of the following events: the patient switched treatments or augmented with another long-acting insulin, the patient developed cancer, death, the study ended, or one year after the patient’s last visit in the database.</p><p>Only patients with dose data for the insulin treatment that they initiated are included in this analysis.</p><p>Association between long-acting insulin use and cancer for new users by dose category (As-Treated Analysis).</p