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Oral diabetes medication monotherapy and short-term mortality in individuals with type 2 diabetes and coronary artery disease
  1. Sridharan Raghavan1,2,3,
  2. Wenhui G Liu1,
  3. David R Saxon1,4,
  4. Gary K Grunwald1,5,
  5. Thomas M Maddox6,
  6. Jane E B Reusch1,4,
  7. Seth A Berkowitz7,
  8. Liron Caplan1,8
  1. 1 Section of Hospital Medicine, Veterans Affairs Eastern Colorado Healthcare System, Denver, Colorado, USA
  2. 2 Division of General Internal Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
  3. 3 Colorado Cardiovascular Outcomes Research Consortium, Aurora, Colorado, USA
  4. 4 Division of Endocrinology, University of Colorado School of Medicine, Aurora, Colorado, USA
  5. 5 Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado, USA
  6. 6 Division of Cardiology, Washington University School of Medicine, St Louis, Missouri, USA
  7. 7 Division of General Medicine and Clinical Epidemiology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
  8. 8 Division of Rheumatology, University of Colorado School of Medicine, Aurora, Colorado, USA
  1. Correspondence to DrSridharanRaghavan; sridharan.raghavan{at}ucdenver.edu

Abstract

Objective To determine whether sulfonylurea use, compared with non-sulfonylurea oral diabetes medication use, was associated with 2-year mortality in individuals with well-controlled diabetes and coronary artery disease (CAD).

Research design and methods We studied 5352 US veterans with type 2 diabetes, obstructive CAD on coronary angiography, hemoglobin A1c ≤7.5% at the time of catheterization, and taking zero or one oral diabetes medication (categorized as no medications, non-sulfonylurea medication, or sulfonylurea). We estimated the association between medication category and 2-year mortality using inverse probability of treatment-weighted (IPW) standardized mortality differences and IPW multivariable Cox proportional hazards regression.

Results 49%, 35%, and 16% of the participants were on no diabetes medications, non-sulfonylurea medications, and sulfonylureas, respectively. In individuals on no medications, non-sulfonylurea medications, and sulfonylureas, the unadjusted mortality rates were 6.6%, 5.2%, and 11.9%, respectively, and the IPW-standardized mortality rates were 5.9%, 6.5%, and 9.7%, respectively. The standardized absolute 2-year mortality difference between non-sulfonylurea and sulfonylurea groups was 3.2% (95% CI 0.7 to 5.7) (p=0.01). In Cox proportional hazards models, the point estimate suggested that sulfonylurea use might be associated with greater hazard of mortality than non-sulfonylurea medication use, but this finding was not statistically significant (HR 1.38 (95% CI 1.00 to 1.93), p=0.05). We did not observe significant mortality differences between individuals on no diabetes medications and non-sulfonylurea users.

Conclusions Sulfonylurea use was common (nearly one-third of those taking medications) and was associated with increased 2-year mortality in individuals with obstructive CAD. The significance of the association between sulfonylurea use and mortality was attenuated in fully adjusted survival models. Caution with sulfonylurea use may be warranted for patients with well-controlled diabetes and CAD, and metformin or newer diabetes medications with cardiovascular safety data could be considered as alternatives when individualizing therapy.

  • diabetes mellitus
  • coronary artery disease
  • oral diabetes treatment
  • metformin
  • sulfonylurea

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors SR, WGL, and DRS conceived of and designed the study; WGL and TMM contributed to data acquisition and availability; SR, WGL, and GKG contributed to analysis plan refinement and performed all data analyses. All authors contributed to interpretation of the results, as well as to drafting and critical revision of the manuscript. All authors approved of the version submitted for review and publication.

  • Funding SR is supported by a University of Colorado School of Medicine, Division of General Internal Medicine Small Grant and American Heart Association Award 17MCPRP33670728. DRS was supported by the VA Advanced Fellowship Program in HSR&D. LC is supported by VA HSR&D IIR 14-048-3. SAB is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number K23DK109200. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval The local VA Research and Development Committee and the Colorado Multiple Institutional Review Board provided approval for this study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement A limited dataset without identifiable participant data is available on request.

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