Cancer Incidence Among Those Initiating Insulin Therapy With Glargine Versus Human NPH Insulin

  1. John B. Buse, MD, PHD8
  1. 1Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  2. 2Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  3. 3Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  4. 4General Medicine Division, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts
  5. 5Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Korea
  6. 6Department of Endocrinology, Ochsner Medical Center, New Orleans, Louisiana
  7. 7Inovalon, Inc., Bowie, Maryland
  8. 8Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
  1. Corresponding author: John B. Buse, jbuse{at}


OBJECTIVE To add to the evidence on comparative long-term effects of insulin analogue glargine versus human neutral protamine Hagedorn (NPH) insulin on the risk for cancer.

RESEARCH DESIGN AND METHODS We identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon MORE2 Registry between January 2003 and December 2010. Patients were required to have a second prescription of the same insulin within 180 days and to be free of cancer. We balanced cohorts on risk factors for cancer outcomes based on comorbidities, comedication, and health care use during the prior 12 months using inverse probability of treatment weighting. Incident cancer was defined as having two claims for cancer (any cancer) or the same cancer (breast, prostate, colon) within 2 months. We estimated adjusted hazard ratios (HRs) and their 95% CI using weighted Cox models censoring for stopping, switching, or augmenting insulin treatment, end of enrollment, and mortality.

RESULTS More patients initiated glargine (43,306) than NPH (9,147). Initiators of glargine were followed for 1.2 (1.1) years and 50,548 (10,011) person-years; 993 (178) developed cancer, respectively. The overall HR was 1.12 (95% CI 0.95–1.32). Results were consistent for breast cancer, prostate cancer, and colon cancer; various durations of treatment; and sensitivity analyses.

CONCLUSIONS Patients initiating insulin glargine rather than NPH do not seem to be at an increased risk for cancer. While our study contributes significantly to our evidence base for long-term effects, this evidence is very limited mainly based on actual dynamics in insulin prescribing.

  • Received January 31, 2013.
  • Accepted May 17, 2013.

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