Risk of hypoglycemia associated with repaglinide combined with clopidogrel, a retrospective cohort study
Abstract Background Repaglinide is widely prescribed to reduce postprandial hyperglycemia and elevated glycated hemoglobin (HbA1c) levels associated with type 2 diabetes, and clopidogrel is a thienopyridine antiplatelet agent and widely used in cardiovascular and cerebrovascular diseases. It has bee...
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Journal of Pharmaceutical Health Care and Sciences |
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| Online Access: | http://link.springer.com/article/10.1186/s40780-020-00159-7 |
| _version_ | 1811324990774050816 |
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| author | Yuuki Akagi Akiko Iketaki Haruna Kimura Yuki Matsudaira Takami Yoshida Takahiro Nishimura Yohei Kawano Yasunari Mano Erina Shigematsu Makoto Ujihara |
| author_facet | Yuuki Akagi Akiko Iketaki Haruna Kimura Yuki Matsudaira Takami Yoshida Takahiro Nishimura Yohei Kawano Yasunari Mano Erina Shigematsu Makoto Ujihara |
| author_sort | Yuuki Akagi |
| collection | DOAJ |
| description | Abstract Background Repaglinide is widely prescribed to reduce postprandial hyperglycemia and elevated glycated hemoglobin (HbA1c) levels associated with type 2 diabetes, and clopidogrel is a thienopyridine antiplatelet agent and widely used in cardiovascular and cerebrovascular diseases. It has been suggested that the concomitant use of repaglinide with clopidogrel may inhibit repaglinide metabolism, because repaglinide is a substrate of cytochrome P450 2C8 (CYP2C8) and the main metabolite of clopidogrel acyl-β-D-glucuronide inhibits CYP2C8 activity. In this study, we retrospectively investigated the effect of clopidogrel with repaglinide on plasma glucose and the risk of hypoglycemia associated with the combination of both drugs. Method Patients were taking clopidogrel (75 mg/day) and started taking glinide (1.5 mg/day repaglinide or 30 mg/day mitiglinide) for the first time from April 2012 to March 2017. We targeted subjects who were hospitalized at the start of glinide and whose preprandial plasma glucose was measured by a nurse. The glucose levels were collected for up to 5 days before and after the glinide start date. Results Average fasting plasma glucose levels (before breakfast) in the repaglinide and clopidogrel group before and after starting repaglinide were 180.1±35.5 and 136.5 ± 44.1 mg/dL, with a mean decrease of 43.6 ± 33.6 mg/dL. In contrast, there was only a moderate decrease of 11.6 ± 30.0 mg/dL in the mitiglinide and clopidogrel group. Minimum plasma glucose levels in the repaglinide and clopidogrel group before and after starting repaglinide were 145.2 ± 42.9 and 93.3 ± 36.3 mg/dL, respectively. Decrease in minimum levels after starting glinide in the repaglinide and clopidogrel group (51.9 ± 47.5 mg/dL) was more significant than those in the mitiglinide and clopidogrel group (only 2.1 ± 29.1 mg/dL), and the repaglinide group (without clopidogrel, 15.5 ± 20.0 mg/dL). Hypoglycemia was observed in 6 of 15 patients in the repaglinide and clopidogrel group, but only 1 of 15 patients in the mitiglinide and clopidogrel group, and no patients in the repaglinide group. Conclusion These findings indicate that minimum plasma glucose levels were significantly decreased in patients taking repaglinide and clopidogrel. Considering the risk of hypoglycemia associated with taking repaglinide and clopidogrel, when a glinide is required in patients taking clopidogrel, mitiglinide may be a better choice. |
| first_indexed | 2024-04-13T14:25:20Z |
| format | Article |
| id | doaj.art-7d5302d459634e67b28c17c3e1918fab |
| institution | Directory Open Access Journal |
| issn | 2055-0294 |
| language | English |
| last_indexed | 2024-04-13T14:25:20Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Pharmaceutical Health Care and Sciences |
| spelling | doaj.art-7d5302d459634e67b28c17c3e1918fab2022-12-22T02:43:21ZengBMCJournal of Pharmaceutical Health Care and Sciences2055-02942020-03-01611710.1186/s40780-020-00159-7Risk of hypoglycemia associated with repaglinide combined with clopidogrel, a retrospective cohort studyYuuki Akagi0Akiko Iketaki1Haruna Kimura2Yuki Matsudaira3Takami Yoshida4Takahiro Nishimura5Yohei Kawano6Yasunari Mano7Erina Shigematsu8Makoto Ujihara9Department of Pharmacy, National Hospital Organization Yokohama Medical CenterDepartment of Pharmacy, National Hospital Organization Yokohama Medical CenterDepartment of Pharmacy, National Hospital Organization Yokohama Medical CenterDepartment of Pharmacy, National Hospital Organization Yokohama Medical CenterDepartment of Pharmacy, National Hospital Organization Yokohama Medical CenterDepartment of Pharmacy, National Cancer Center Hospital EastFaculty of Pharmaceutical Sciences, Tokyo University of ScienceFaculty of Pharmaceutical Sciences, Tokyo University of ScienceDepartment of Clinical Laboratory, National Hospital Organization Yokohama Medical CenterDepartment of Diabetes Endocrinology, National Hospital Organization Yokohama Medical CenterAbstract Background Repaglinide is widely prescribed to reduce postprandial hyperglycemia and elevated glycated hemoglobin (HbA1c) levels associated with type 2 diabetes, and clopidogrel is a thienopyridine antiplatelet agent and widely used in cardiovascular and cerebrovascular diseases. It has been suggested that the concomitant use of repaglinide with clopidogrel may inhibit repaglinide metabolism, because repaglinide is a substrate of cytochrome P450 2C8 (CYP2C8) and the main metabolite of clopidogrel acyl-β-D-glucuronide inhibits CYP2C8 activity. In this study, we retrospectively investigated the effect of clopidogrel with repaglinide on plasma glucose and the risk of hypoglycemia associated with the combination of both drugs. Method Patients were taking clopidogrel (75 mg/day) and started taking glinide (1.5 mg/day repaglinide or 30 mg/day mitiglinide) for the first time from April 2012 to March 2017. We targeted subjects who were hospitalized at the start of glinide and whose preprandial plasma glucose was measured by a nurse. The glucose levels were collected for up to 5 days before and after the glinide start date. Results Average fasting plasma glucose levels (before breakfast) in the repaglinide and clopidogrel group before and after starting repaglinide were 180.1±35.5 and 136.5 ± 44.1 mg/dL, with a mean decrease of 43.6 ± 33.6 mg/dL. In contrast, there was only a moderate decrease of 11.6 ± 30.0 mg/dL in the mitiglinide and clopidogrel group. Minimum plasma glucose levels in the repaglinide and clopidogrel group before and after starting repaglinide were 145.2 ± 42.9 and 93.3 ± 36.3 mg/dL, respectively. Decrease in minimum levels after starting glinide in the repaglinide and clopidogrel group (51.9 ± 47.5 mg/dL) was more significant than those in the mitiglinide and clopidogrel group (only 2.1 ± 29.1 mg/dL), and the repaglinide group (without clopidogrel, 15.5 ± 20.0 mg/dL). Hypoglycemia was observed in 6 of 15 patients in the repaglinide and clopidogrel group, but only 1 of 15 patients in the mitiglinide and clopidogrel group, and no patients in the repaglinide group. Conclusion These findings indicate that minimum plasma glucose levels were significantly decreased in patients taking repaglinide and clopidogrel. Considering the risk of hypoglycemia associated with taking repaglinide and clopidogrel, when a glinide is required in patients taking clopidogrel, mitiglinide may be a better choice.http://link.springer.com/article/10.1186/s40780-020-00159-7RepaglinideClopidogrelDrug-drug interactionHypoglycemiaCytochrome P450 2C8Mitiglinide |
| spellingShingle | Yuuki Akagi Akiko Iketaki Haruna Kimura Yuki Matsudaira Takami Yoshida Takahiro Nishimura Yohei Kawano Yasunari Mano Erina Shigematsu Makoto Ujihara Risk of hypoglycemia associated with repaglinide combined with clopidogrel, a retrospective cohort study Journal of Pharmaceutical Health Care and Sciences Repaglinide Clopidogrel Drug-drug interaction Hypoglycemia Cytochrome P450 2C8 Mitiglinide |
| title | Risk of hypoglycemia associated with repaglinide combined with clopidogrel, a retrospective cohort study |
| title_full | Risk of hypoglycemia associated with repaglinide combined with clopidogrel, a retrospective cohort study |
| title_fullStr | Risk of hypoglycemia associated with repaglinide combined with clopidogrel, a retrospective cohort study |
| title_full_unstemmed | Risk of hypoglycemia associated with repaglinide combined with clopidogrel, a retrospective cohort study |
| title_short | Risk of hypoglycemia associated with repaglinide combined with clopidogrel, a retrospective cohort study |
| title_sort | risk of hypoglycemia associated with repaglinide combined with clopidogrel a retrospective cohort study |
| topic | Repaglinide Clopidogrel Drug-drug interaction Hypoglycemia Cytochrome P450 2C8 Mitiglinide |
| url | http://link.springer.com/article/10.1186/s40780-020-00159-7 |
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