Volume 108, Issue 5 p. 1010-1017
Article

Sulfonylureas and Metformin Were Not Associated With an Increased Rate of Serious Bleeding in Warfarin Users: A Self-Controlled Case Series Study

Young Hee Nam

Young Hee Nam

Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA

Search for more papers by this author
Xu Han

Xu Han

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Search for more papers by this author
Colleen M. Brensinger

Colleen M. Brensinger

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Search for more papers by this author
Warren B. Bilker

Warren B. Bilker

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Search for more papers by this author
Charles E. Leonard

Charles E. Leonard

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Search for more papers by this author
Sean Hennessy

Corresponding Author

Sean Hennessy

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Correspondence: Sean Hennessy ([email protected])

Search for more papers by this author
First published: 11 May 2020
Citations: 4

Abstract

Drug interactions between warfarin and sulfonylureas are suggested by pharmacokinetic information and prior studies. However, clinical evidence on the association of such interactions and the risk of bleeding is lacking. Using healthcare claims data from 5 US Medicaid programs from 1999–2011 and a self-controlled case series design with warfarin as an object drug, we calculated confounder-adjusted rate ratios (RRs) for concomitant use of sulfonylureas and metformin for 3 outcomes separately: (i) serious bleeding as a composite outcome of gastrointestinal bleeding (GIB) and nontraumatic intracranial hemorrhage (ICH); (ii) GIB; and (iii) ICH. In 6,463 warfarin users experiencing serious bleeding, an increased rate of serious bleeding was not associated with concomitant use of glimepiride (RR: 0.93; 95% confidence interval (CI) 0.75–1.15), glipizide (RR: 0.97; 95% CI 0.84–1.13), glyburide (RR: 0.89; 95% CI 0.76–1.06), or metformin (RR: 0.85; 95% CI 0.76–0.96), nor was the occurrence of the component outcomes of GIB or ICH. These results suggest that use of sulfonylureas or metformin was not associated with an increased rate of serious bleeding in warfarin users.

Conflict of Interest

S.H. consulted for Merck Research Laboratories and the Medullary Thyroid Cancer Consortium (Novo Nordisk Inc., AstraZeneca Pharmaceuticals LP, GlaxoSmithKline LLC, and Eli Lilly and Company) on topics unrelated to this submitted work, and leads a training program that receives support from Pfizer Inc., unrelated to this submitted work. C.E.L. serves on the executive committee of this training program that receives support from Pfizer Inc. All the other authors declared no conflict of interests.

Data Availability Statement

Medicaid and Medicare claims data are available via a data use agreement with the Centers for Medicare and Medicaid Services (CMS) (https://www.cms.gov/). The authors did not have any special access privileges that others would not have. The procedures to obtain access to these data are described in the CMS website (https://www.cms.gov/Research-Statistics-Data-and-Systems/Files-for-Order/Data-Disclosures-Data-Agreements/Researchers) and the Research Data Assistance Center (ResDAC) website (https://www.resdac.org/research-identifiable-files-rif-requests).