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Permanent link (DOI): https://doi.org/10.7939/R31S9H

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Antidiabetic agents and cancer outcomes: Are there differences between agents? Open Access

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Other title
Subject/Keyword
type 2 diabetes mellitus
cancer
antidiabetic agents
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Bowker, Samantha Lyndsey
Supervisor and department
Johnson, Jeff (Department of Public Health Sciences, University of Alberta)
Yasui, Yutaka (Department of Public Health Sciences, University of Alberta)
Veugelers, Paul (Department of Public Health Sciences, University of Alberta)
Examining committee member and department
Brancati, Fredrick (School of Medicine, Johns Hopkins University)
Lynd, Larry (Faculty of Pharmaceutical Sciences, University of British Columbia)
Johnson, Jeff (Department of Public Health Sciences, University of Alberta)
Veugelers, Paul (Department of Public Health Sciences, University of Alberta)
Voaklander, Don (Department of Public Health Sciences, University of Alberta)
Yasui, Yutaka (Department of Public Health Sciences, University of Alberta)
Department
Department of Public Health Sciences
Specialization

Date accepted
2009-09-22T20:09:20Z
Graduation date
2009-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
There is substantial evidence of the elevated risk of cancer among individuals with type 2 diabetes. Very little is known, however, about the role that antidiabetic therapies play in this relationship. The objective of this program of research was to examine whether there is a therapeutic risk associated with antidiabetic therapies that increase circulating insulin levels, such as sulfonylureas and exogenous insulin, or a therapeutic benefit associated with antidiabetic therapies that reduce insulin resistance, such as metformin and the glitazones. This objective was achieved through four related population-based cohort studies using the administrative databases from Saskatchewan Health. The first study looked at the effect of the older antidiabetic therapies metformin and sulfonylureas on cancer mortality. The focus of the second study was to explore more closely the effect of metformin and sulfonylurea by using a time-varying Cox regression to define drug exposures. The third study looked more closely at the effect of exogenous insulin therapy and cancer mortality, and the last study focused on the more recently available antidiabetic therapy the glitazones and cancer mortality. We found that individuals with type 2 diabetes exposed to sulfonylurea monotherapy had a significantly increased risk of cancer-related mortality, compared to patients exposed to metformin. We also observed a dose-response gradient with exogenous insulin therapy and cancer mortality, whereby individuals exposed to higher levels of insulin had a higher risk of cancer mortality. In the last study, we found that the newer class of antidiabetic therapies, the glitazones, were associated with a decreased risk of cancer mortality. These finding add further support that antidiabetic therapies may play a moderating role in the relationship between type 2 diabetes and cancer outcomes. However, it is unclear whether the increased risk of cancer mortality we observed was related to a toxic effect of sulfonylureas and exogenous insulin or a protective effect of metformin and glitazones, or due to some unmeasured effect related to both choice of drug therapy and cancer risk. Future research should incorporate a non-diabetes control cohort for comparison and examine the more proximal outcome measure cancer incidence.
Language
English
DOI
doi:10.7939/R31S9H
Rights
License granted by Samantha Bowker (sbowker@ualberta.ca) on 2009-09-22T19:58:50Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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