Mortality among veterans with type 2 diabetes initiating metformin, sulfonylurea or rosiglitazone monotherapy
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Despite oral hypoglycaemic medications being the most commonly used pharmacological treatments for type 2 diabetes, research is limited on their comparative safety, particularly their effects on overall mortality. We compared mortality risk with monotherapy initiation of four oral hypoglycaemic medications in a nationwide cohort of US veterans with type 2 diabetes.
We identified new users of oral hypoglycaemic medication monotherapy between 2004 and 2009 who received care for at least 1 year from the Veterans Health Administration. Patients were followed until initial monotherapy discontinuation, addition of another diabetes pharmacotherapy, death or end of follow-up. Mortality HRs were estimated using Cox regression adjusted for potential confounding factors.
Among new users of metformin, sulfonylureas and rosiglitazone (185,360 men, 7,812 women), 4,256 (2.2%) died during follow-up. Average duration of medication use ranged from 1.4 to 1.7 years. Significantly higher mortality risk was seen for glibenclamide (known as glyburide in the USA and Canada) (HR 1.38, 95% CI 1.27, 1.50) or glipizide (HR 1.55, 95% CI 1.43, 1.67) compared with metformin monotherapy, and for glipizide compared with rosiglitazone (HR 1.27, 95% CI 1.01, 1.59) or glibenclamide monotherapy (HR 1.12, 95% CI 1.02, 1.23). A significant sex–rosiglitazone interaction was seen (p = 0.034) compared with metformin monotherapy, with women having a higher HR (HR 4.36, 95% CI 1.34, 14.20) than men (HR 1.19, 95% CI 0.95, 1.49).
Significantly higher mortality was associated with glibenclamide, glipizide and rosiglitazone use compared with metformin, and with glipizide use compared with rosiglitazone or glibenclamide. The potential for residual confounding by indication should be considered in interpreting these results.
KeywordsCohort study Diabetes mellitus Monotherapy Mortality Oral hypoglycaemic medication Pharmacoepidemiology Veterans
Epidemiologic Research and Information Center
Veterans Health Administration
Veterans Integrated Service Network
The Seattle Epidemiologic Research and Information Center (ERIC) is part of the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development, Washington, DC, USA. The content of this article does not necessarily represent the views of the Department of Veterans Affairs or the US Government. We are grateful to S. E. Kahn, VA Puget Sound in Seattle, for his careful reading of and suggestions for this manuscript.
This work was supported by the ERIC of VA Puget Sound in Seattle, and by facilities and services provided by the Diabetes Research Center (DK-17047) at the University of Washington. VA Puget Sound Health Care System provided support for the involvement of E. J. Boyko, N. L. Smith and S. Wheeler in this research. J. S. Floyd was supported by National Heart, Lung and Blood Institute training grant T32 HL007902.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
SW and EJB made substantial contributions to the conception and design of the study, drafted the article and provided approval for the final version. KM and KR acquired the data, revised the article critically for important intellectual content and provided approval for the final version. CWF, JSF and NLS analysed and interpreted the data, revised the article critically for important intellectual content and provided approval for the final version. EJB and SW had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
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