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Impact of pioglitazone regulatory withdrawal on antidiabetic drug use and health in diabetic patients

  • Pharmacoepidemiology and Prescription
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Abstract

Purpose

In 2011, pioglitazone was withdrawn from the French market owing to a potential risk of bladder cancer. This study aimed at assessing the impact of this pioglitazone withdrawal (PW) considering (i) trends in antidiabetic uses and (ii) changes in hospitalization/death rates in diabetic patients following PW.

Methods

We first considered the general population of the Echantillon Généraliste des Bénéficiaires (EGB), a 1/97th representative sample of the French healthcare insurance system beneficiaries, for the 2010–2014 period. In this, for each non-insulinic antidiabetic drug class, changes within the numbers of monthly supplied drug units for 1000 subjects were studied through times series and Unobserved Component Models. Second, we identified from the EGB a cohort of patients who were delivered a non-insulinic antidiabetic between 01 April 2011 and 01 August 2011 (date of PW). In this, post-withdrawal incidences of all-cause hospitalization and death were compared amongst pioglitazone users and non-users using proportional subdistribution hazards models.

Results

PW was accompanied by an increase in metformin (+ 11.7; 95% CI 1.1–22.3) and glinide (+ 11.0; 95% CI 1.2–20.8) numbers of monthly supplied units for 1000 subjects. No significant change was found for GLP-1 agonists, DPP-4 inhibitors, sulphonylureas or alpha-glucosidase inhibitors. In the cohort of non-insulinic antidiabetic users at the time of PW (1093 pioglitazone users, 17,900 non-users), being a pioglitazone user at PW was not associated with a subsequently higher rate of hospitalization.

Conclusions

If PW was accompanied with significant changes in the use of some antidiabetics, no adverse impact of PW on hospitalization or death rates of diabetic type 2 patients was found.

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Acknowledgements

The present study is part of the Drugs Systematized Assessment in real-liFe Environment (DRUGS-SAFE) research program that is funded by the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM); grants received for the year 2015: 900,000 €). This program aims at providing an integrated system allowing the concomitant monitoring of drug use and safety in France. The potential impact of drugs (e.g. psychotropics), frailty of populations, and seriousness of risks drives the research program. This publication represents the views of the authors and does not necessarily represent the opinion of the French Medicines Agency.

Funding

The present study is part of the Drugs Systematized Assessment in real-liFe Environment (DRUGS-SAFE) research program that is funded by the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM); grants received for the year 2015: 900,000 €). University of Bordeaux—Initiative for Excellence IdEX—Health Determinants in Society (HEADS). Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM).

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Authors and Affiliations

  1. Inserm, Bordeaux Population Health Research Center, team Pharmacoepidemiology, UMR 1219, University of Bordeaux, 33000, Bordeaux, France

    Antoine Pariente, Yohann Mansiaux, Ana Jarné, Francesco Salvo, Cécile Pageot, Julien Bezin & Bernard Bégaud

  2. Pole de Sante Publique, Service de Pharmacologie Medicale, Centre de Pharmacovigilance, CHU de Bordeaux, 33000, Bordeaux, France

    Antoine Pariente, Cécile Pageot, Julien Bezin & Bernard Bégaud

  3. Direction de la Recherche Clinique et de l’Innovation, CHU de Bordeaux, 33400, Talence, France

    Francesco Salvo

  4. Centre Emile Durkheim, University of Bordeaux, 33000, Bordeaux, France

    Andy Smith

Authors
  1. Antoine Pariente
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  2. Yohann Mansiaux
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  3. Ana Jarné
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  4. Francesco Salvo
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  5. Cécile Pageot
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  6. Julien Bezin
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  7. Andy Smith
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  8. Bernard Bégaud
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Contributions

Antoine Pariente conceptualized and designed the study, interpreted the data, drafted the initial manuscript, approved the final version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Yohann Mansiaux, Ana Jarné, Mr. Mansiaux and Mrs. Jarné conceptualized and designed the study, acquired data and carried out the analysis, critically revised the manuscript, approved the final version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Francesco Salvo, Cécile Pageot, Julien Bezin, Andy Smith, Bernard Bégaud, Dr. Salvo, Dr. Pageot, Dr. Bezin, Pr. Smith and Pr. Bégaud conceptualized and designed the study, interpreted the data, critically revised the manuscript, approved the final version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Antoine Pariente.

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The authors declare that they have no conflict of interest.

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Pariente, A., Mansiaux, Y., Jarné, A. et al. Impact of pioglitazone regulatory withdrawal on antidiabetic drug use and health in diabetic patients. Eur J Clin Pharmacol 73, 1655–1663 (2017). https://doi.org/10.1007/s00228-017-2326-z

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  • DOI: https://doi.org/10.1007/s00228-017-2326-z

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