Incidence of type 2 diabetes mellitus and hyperlipidemia in patients prescribed dasatinib or nilotinib as first- or second-line therapy for chronic myelogenous leukemia in the US

Abstract

Objective: Evaluate the incidence of type 2 diabetes mellitus (T2DM) and hyperlipidemia (HLD) in CML patients initiating therapy with dasatinib or nilotinib.

Methods: Retrospective study using MarketScan claims from January 2006 to December 2014. The first analysis evaluated occurrence of T2DM, defined as ≥2 claims with a T2DM ICD-9 code or 1 diagnosis claim and an antidiabetic medication. The second analysis evaluated occurrence of HLD, defined as ≥2 claims with an HLD ICD-9 code, or 1 diagnosis claim and an anti-HLD medication. Incidence rates were computed as number of events divided by sum of person years (PY) at risk for all subjects. Multivariate Cox proportional hazards models estimated hazard ratios (HRs) for T2DM or HLD.

Results: There were 2004 and 1280 patients who met the criteria for the T2DM analysis (n = 1272 dasatinib, n = 732 nilotinib) and HLD analysis (n = 845 dasatinib, n = 435 nilotinib). The incidence rate of T2DM was 40.4 per 1000 PY (95% CI: 27.60, 56.98) for nilotinib and 17.6 per 1000 PY (95% CI: 11.14, 26.38) for dasatinib. HR for occurrence of T2DM was 2.77 (95% CI: 1.58, 4.86), indicating that patients on nilotinib had a significantly higher adjusted risk for incident T2DM. The incidence rate of HLD was 74.6 per 1000 PY (95% CI: 50.70, 105.94) for nilotinib and 46.4 per 1000 PY (95% CI: 33.00, 63.45) for dasatinib. HR for occurrence of HLD was 1.75 (95% CI: 1.07, 2.87) indicating that patients on nilotinib had a significantly higher adjusted risk for incident HLD.

Conclusions: Patients receiving nilotinib had significantly higher rates of incident T2DM or HLD than patients on dasatinib.

Keywords:

• CML
• metabolic outcomes
• tyrosine kinase inhibitors
• type 2 diabetes mellitus
• hyperlipidemia

Transparency

Declaration of funding

This study was funded by Bristol-Myers Squibb.

Author contributions: All authors were involved with the study conception and design, analysis interpretation, and writing and revising the manuscript critically for intellectual content. All authors are accountable for all aspects of this work.

Declaration of financial/other relationships

M.F. has disclosed that she is an employee of Franklin Pharmaceutical Consulting, which received funding from Bristol-Myers Squibb in connection with conducting this study and development of this manuscript. S.P. and D.Y. have disclosed that they are full time consultants to Bristol-Myers Squibb. L.B. and D.M. have disclosed that they are employees of Bristol-Myers Squibb and own stock in the company.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

The authors wish to thank Lisa Siegartel MPH, Bristol-Myers Squibb, Princeton, NJ for her assistance with revisions to the paper for intellectual content.