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Benefits and Harms of Deprescribing Antihyperglycemics for Adults With Type 2 Diabetes: A Systematic Review

  • ZhiDi Deng
    Affiliations
    Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
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  • Wade Thompson
    Affiliations
    Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada

    Research Unit of General Practice, University of Southern Denmark, Odense, Denmark

    Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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  • Clara Korenvain
    Affiliations
    Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada
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  • Iliana C. Lega
    Affiliations
    Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada

    Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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  • Barbara Farrell
    Affiliations
    Bruyère Research Institute, Ottawa, Ontario, Canada

    Department of Family Medicine, University of Ottawa, Ottawa, Ontario, Canada

    School of Pharmacy, University of Waterloo, Kitchener, Ontario, Canada
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  • Heather Lochnan
    Affiliations
    Department of Medicine, Division of Endocrinology and Metabolism–Riverside Campus, The Ottawa Hospital, Ottawa, Ontario, Canada
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  • Lisa M. McCarthy
    Correspondence
    Address for correspondence: Lisa M. McCarthy PharmD, MSc, Institute for Better Health, Trillium Health Partners, 100 Queensway West–Clinical Administrative Building, Mississauga, Ontario L5B 1B8, Canada.
    Affiliations
    Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

    Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada

    Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

    Bruyère Research Institute, Ottawa, Ontario, Canada

    School of Pharmacy, University of Waterloo, Kitchener, Ontario, Canada

    Institute for Better Health, Trillium Health Partners, Mississauga, Ontario, Canada
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Published:February 02, 2022DOI:https://doi.org/10.1016/j.jcjd.2022.01.009

      Abstract

      Objectives

      Contemporary guidelines suggest relaxed glycemic targets in populations with type 2 diabetes mellitus (T2DM) at risk of hypoglycemia, including people with multimorbidity, limited life expectancy, or frailty. However, overtreatment remains commonplace. To inform safe deprescribing, a previous systematic review investigated the benefits and harms of deprescribing antihyperglycemics, but identified only limited, very low-quality evidence. We sought to update that review and identify and describe newly published literature on the effects of deprescribing antihyperglycemics in older adults with T2DM.

      Methods

      We searched MEDLINE, EMBASE and the Cochrane Library (July 2015 to January 2021) for controlled studies published in English addressing the effects of deprescribing vs continuing antihyperglycemics in adults with T2DM. Two independent reviewers performed title, abstract and full-text screening, data extraction and risk-of-bias assessment. Cochrane’s risk-of-bias tools, RoB2 and ROBINS-I were used. The findings were summarised narratively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) was used to evaluate the evidence.

      Results

      We identified 4 additional investigations—2 randomized controlled trials and 2 retrospective cohort studies. After deprescribing, 3 studies reported no clinically significant changes in glucose control and 2 studies reported reductions in adverse events (e.g. hypoglycemia, all-cause mortality and nonspine fractures). However, based on GRADE assessment, we found very low certainty of the evidence due to concerns of risk of bias (e.g. unmeasured confounding), imprecision, and indirectness.

      Conclusions

      Deprescribing antihyperglycemic medications in older adults with T2DM is likely feasible and safe, and benefits may outweigh the harms. However, the evidence indicates very low certainty. Additional deprescribing studies are needed with rigourous methodologies and reporting.

      Résumé

      Objectifs

      Les lignes directrices contemporaines font état de valeurs cibles assouplies de la glycémie pour les populations atteintes du diabète sucré de type 2 (DST2) qui sont exposées au risque d’hypoglycémie, notamment les personnes qui présentent une multimorbidité, une espérance de vie limitée ou une fragilité, mais le surtraitement demeure courant. Pour orienter les cliniciens sur la déprescription sécuritaire, une revue systématique antérieure a porté sur les avantages et les inconvénients de la déprescription des antihyperglycémiants, mais a seulement permis de relever des données probantes limitées de très faible qualité. Nous avons cherché à actualiser cette revue, et à déterminer et à décrire la littérature récemment publiée sur les effets de la déprescription des antihyperglycémiants chez les personnes âgées atteintes du DST2.

      Méthodes

      Nous avons effectué des recherches dans MEDLINE, Embase et Cochrane Library (de juillet 2015 à janvier 2021) pour trouver des études comparatives publiées en anglais qui portaient sur les effets de la déprescription vs la poursuite des antihyperglycémiants chez les adultes atteints du DST2. Deux examinateurs indépendants ont effectué le filtrage des titres, des résumés et des textes intégraux, l’extraction des données et l’évaluation du risque de biais. Les outils d’évaluation du risque de biais de Cochrane, RoB2 et ROBINS-I, ont été utilisés. Les résultats ont fait l’objet d’une synthèse narrative. Le GRADE (Grading of Recommendations, Assessment, Development and Evaluations) a été utilisé pour évaluer les données probantes.

      Résultats

      Nous avons trouvé 4 autres études—2 essais comparatifs à répartition aléatoire et 2 études de cohorte rétrospectives. Après la déprescription, 3 études ne faisaient état d’aucun changement cliniquement significatif de la régulation de la glycémie et 2 études faisaient état d’une réduction des événements indésirables (p. ex. l’hypoglycémie, la mortalité toutes causes confondues et les fractures non vertébrales). Toutefois, selon l’évaluation GRADE, nous avons observé des données probantes de très faible certitude en raison des préoccupations sur le risque de biais (p. ex. les facteurs de confusion non mesurés), l’imprécision et le caractère indirect).

      Conclusions

      La déprescription des médicaments antihyperglycémiques chez les personnes âgées atteintes du DST2 est probablement faisable et sécuritaire, et les avantages peuvent l’emporter sur les inconvénients. Toutefois, les données probantes montrent une très faible certitude. D’autres études qui portent sur la déprescription et qui sont basées sur des méthodologies et des comptes rendus rigoureux sont nécessaires.

      Keywords

      Mots clés

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      References

        • ADVANCE Collaborative Group
        Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.
        N Engl J Med. 2008; 358: 2560-2572
        • Diabetes Canada Clinical Practice Guidelines Expert Committee
        Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada.
        Can J Diabetes. 2018; 42: S1-S325
        • American Diabetes Association
        12. Older adults: Standards of medical care in diabetes---2020.
        Diabetes Care. 2020; 43: S152-S162
        • AGS Choosing Wisely Workgroup
        American Geriatrics Society identifies five things that healthcare providers and patients should question.
        J Am Geriatr Soc. 2013; 61: 622-631
        • Niznik J.D.
        • Hunnicutt J.N.
        • Zhao X.
        • et al.
        Deintensification of diabetes medications among Veterans at the end of life in VA nursing homes.
        J Am Geriatr Soc. 2020; 68: 736-745
        • Bouillet B.
        • Vaillant G.
        • Petit J.
        • et al.
        Are elderly patients with diabetes being overtreated in French long-term-care homes?.
        Diabetes Metab. 2010; 36: 272-277
        • Lega I.C.
        • Campitelli M.A.
        • Matlow J.
        • et al.
        glycemic control and use of high-risk antihyperglycemic agents among nursing home residents with diabetes in Ontario, Canada.
        JAMA Intern Med. 2021; 181: 992-994
        • Meneilly G.S.
        • Berard L.D.
        • Cheng A.Y.
        • et al.
        Insights into the current management of older adults with type 2 diabetes in the Ontario primary care setting.
        Can J Diabetes. 2018; 42: 23-30
        • Makam A.N.
        • Nguyen O.K.
        An evidence-based medicine approach to antihyperglycemic therapy in diabetes mellitus to overcome overtreatment.
        Circulation. 2017; 135: 180-195
        • Spencer-Bonilla G.
        • Quiñones A.R.
        • Montori V.M.
        Assessing the burden of treatment.
        J Gen Intern Med. 2017; 32: 1141-1145
        • Bruyère Research Institute
        What is deprescribing? 2021.
        • Seidu S.
        • Kunutsor S.K.
        • Topsever P.
        • Hambling C.E.
        • Cos F.X.
        • Khunti K.
        Deintensification in older patients with type 2 diabetes: A systematic review of approaches, rates and outcomes.
        Diabetes Obes Metab. 2019; 21: 1668-1679
        • Black C.D.
        • Thompson W.
        • Welch V.
        • et al.
        Lack of evidence to guide deprescribing of antihyperglycemics: A systematic review.
        Diabetes Ther. 2017; 8: 23-31
        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration.
        J Clin Epidemiol. 2009; 62: e1-e34
      1. Higgins JPT, Savović J, Page MJ, Elbers RG, Sterne JAC. Chapter 8: Assessing risk of bias in a randomized trial. In: Higgins JPT, Thomas J, Chandler J, et al, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). 2021. www.training.cochrane.org/handbook. Accessed March 30, 2021.

      2. Sterne JAC, Hernán MA, McAleenan A, Reeves BC, Higgins JPT. Chapter 25: Assessing risk of bias in a non-randomized study. In: Higgins JPT, Thomas J, Chandler J, et al, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). 2021. www.training.cochrane.org/handbook. Accessed March 30, 2021.

      3. Higgins JPT, Thomas J, Chandler J, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). 2021. www.training.cochrane.org/handbook. Accessed March 30, 2021.

        • McMaster University
        (developed by Evidence Prime, Inc). GRADEpro Guideline Development Tool [software].
        (Accessed March 30, 2021)
        • Schwartz A.V.
        • Chen H.
        • Ambrosius W.T.
        • et al.
        Effects of TZD use and discontinuation on fracture rates in ACCORD bone study.
        J Clin Endocrinol Metab. 2015; 100: 4059-4066
        • Kamiyama H.
        • Aoki K.
        • Nakajima S.
        • et al.
        Effect of switching from sulphonylurea to repaglinide twice or three times daily for 4 months on glycemic control in Japanese patients with type 2 diabetes.
        Intern Med. 2016; 55: 1697-1703
        • Omori K.
        • Nomoto H.
        • Nakamura A.
        • et al.
        Reduction in glucose fluctuations in elderly patients with type 2 diabetes using repaglinide: A randomized controlled trial of repaglinide vs sulfonylurea.
        J Diabetes Investig. 2019; 10: 367-374
        • Hui R.L.
        • Chang C.C.
        • Niu F.
        • et al.
        Evaluation of a pharmacist-managed antidiabetic deprescribing program in an integrated health care system.
        J Manag Care Spec Pharm. 2019; 25: 927-934
        • Aspinall S.L.
        • Zhao X.
        • Good C.B.
        • et al.
        Intervention to decrease glyburide use in elderly patients with renal insufficiency.
        Am J Geriatr Pharmacother. 2011; 9: 58-68
        • Sjöblom P.
        • Löfgren U.
        • Lannering C.
        • et al.
        Can diabetes medication be reduced in elderly patients?: An observational study of diabetes drug withdrawal in nursing home patients with tight glycaemic control.
        Diabetes Res Clin Pract. 2008; 82: 197-202
      4. The GRADE Working Group. In: Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations. (updated October 2013). http://guidelinedevelopment.org/handbook. Accessed March 30, 2021.

        • Oktora M.P.
        • Kerr K.P.
        • Hak E.
        • Denig P.
        Rates, determinants and success of implementing deprescribing in people with type 2 diabetes: A scoping review.
        Diabetic Med. 2021; 38e14408
        • Aubert C.E.
        • Kerr E.A.
        • Maratt J.K.
        • Klamerus M.L.
        • Hofer T.P.
        Outcome measures for interventions to reduce inappropriate chronic drugs: A narrative review.
        J Am Geriatr Soc. 2020; 68: 2390-2398
        • Farrell B.
        • Black C.
        • Thompson W.
        • et al.
        Deprescribing antihyperglycemic agents in older persons: Evidence-based clinical practice guideline.
        Can Fam Physician. 2017; 63: 832-843
        • Secrest M.H.
        • Azoulay L.
        • Dahl M.
        • et al.
        A population-based analysis of antidiabetic medications in four Canadian provinces: Secular trends and prescribing patterns.
        Pharmacoepidemiol Drug Saf. 2020; 29: 86-92