Metabolic adverse events associated with systemic corticosteroid therapy—a systematic review and meta-analysis

Objectives To assess the risk of new-onset or worsening hyperglycaemia, hypertension, weight gain and hyperlipidaemia with systemic corticosteroid therapy (CST) as reported in published randomised control trial (RCT) studies.Data sources Literature search using MEDLINE, EMBASE, Cochrane library, Web...

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Published in:BMJ Open
Main Authors: Szilard Nemes, Veronica Phillips, Spoorthy Kulkarni, Hannah Durham, Luke Glover, Osaid Ather, Leslie Cousens, Parmis Blomgran, Philip Ambery
Format: Article
Language:English
Published: BMJ Publishing Group 2022-12-01
Online Access:https://bmjopen.bmj.com/content/12/12/e061476.full
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author Szilard Nemes
Veronica Phillips
Spoorthy Kulkarni
Hannah Durham
Luke Glover
Osaid Ather
Leslie Cousens
Parmis Blomgran
Philip Ambery
author_facet Szilard Nemes
Veronica Phillips
Spoorthy Kulkarni
Hannah Durham
Luke Glover
Osaid Ather
Leslie Cousens
Parmis Blomgran
Philip Ambery
author_sort Szilard Nemes
collection DOAJ
container_title BMJ Open
description Objectives To assess the risk of new-onset or worsening hyperglycaemia, hypertension, weight gain and hyperlipidaemia with systemic corticosteroid therapy (CST) as reported in published randomised control trial (RCT) studies.Data sources Literature search using MEDLINE, EMBASE, Cochrane library, Web of Science and ScopusStudy eligibility criteria Published articles on results of RCT with a systemic CST arm with numerical data presented on adverse effect (AE).Participants and interventions Reports of hyperglycaemia, hypertension, weight gain and hyperlipidaemia associated with systemic CST in patients or healthy volunteer’s ≥17 years of age.Study appraisal methods Risk of bias tool, assessment at the level of AE and key study characteristics.Results A total of 5446 articles were screened to include 118 studies with 152 systemic CST arms (total participants=17 113 among which 8569 participants treated with CST). Pooled prevalence of hyperglycaemia in the CST arms within the studies was 10% (95% CI 7% to 14%), with the highest prevalence in respiratory illnesses at 22% (95% CI 9% to 35%). Pooled prevalence of severe hyperglycaemia, hypertension, weight gain and hyperlipidaemia within the corticosteroid arms was 5% (95% CI 2% to 9%), 6% (95% CI 4% to 8%), 13% (95% CI 8% to 18%), 8% (95% CI 4% to 17%), respectively. CST was significantly associated hyperglycaemia, hypertension and weight gain as noted in double-blinded placebo-controlled parallel-arms studies: OR of 2.13 (95% CI 1.66 to 2.72), 1.68 (95% CI 0.96 to 2.95) and 5.20 (95% CI 2.10 to 12.90), respectively. Intravenous therapy posed higher risk than oral therapy: OR of 2.39 (95% CI 1.16 to 4.91).Limitations There was significant heterogeneity in the AE definitions and quality of AE reporting in the primary studies and patient populations in the studies. The impact of cumulative dose effect on incidental AE could not be calculated.Conclusions and implications of key findings Systemic CST use is associated with increased risk of metabolic AEs, which differs for each disease group and route of administration.PROSPERO registration number CRD42020161270.
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spelling doaj-art-6eb2e2ebbd7147fba6472f7b607dfc942025-08-20T02:15:58ZengBMJ Publishing GroupBMJ Open2044-60552022-12-01121210.1136/bmjopen-2022-061476Metabolic adverse events associated with systemic corticosteroid therapy—a systematic review and meta-analysisSzilard Nemes0Veronica Phillips1Spoorthy Kulkarni2Hannah Durham3Luke Glover4Osaid Ather5Leslie Cousens6Parmis Blomgran7Philip Ambery8Data Science & AI, R&D BioPharmaceuticals, AstraZeneca, Gothenburg, SwedenMedical Library, School of Clinical Medicine, University of Cambridge, Cambridge, UKClinical Pharmacology and Therapeutics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UKDepartment of Urology, Imperial College Healthcare NHS Trust, London, UKDepartment of Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UKStructural & Chemical Biology, The Francis Crick Institute, London, UKRespiratory & Immunology, AstraZeneca R&D Boston, Waltham, Massachusetts, USAEarly Respiratory & Immunology, AstraZeneca R&D Gothenburg, Mölndal, SwedenClinical Late Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, SwedenObjectives To assess the risk of new-onset or worsening hyperglycaemia, hypertension, weight gain and hyperlipidaemia with systemic corticosteroid therapy (CST) as reported in published randomised control trial (RCT) studies.Data sources Literature search using MEDLINE, EMBASE, Cochrane library, Web of Science and ScopusStudy eligibility criteria Published articles on results of RCT with a systemic CST arm with numerical data presented on adverse effect (AE).Participants and interventions Reports of hyperglycaemia, hypertension, weight gain and hyperlipidaemia associated with systemic CST in patients or healthy volunteer’s ≥17 years of age.Study appraisal methods Risk of bias tool, assessment at the level of AE and key study characteristics.Results A total of 5446 articles were screened to include 118 studies with 152 systemic CST arms (total participants=17 113 among which 8569 participants treated with CST). Pooled prevalence of hyperglycaemia in the CST arms within the studies was 10% (95% CI 7% to 14%), with the highest prevalence in respiratory illnesses at 22% (95% CI 9% to 35%). Pooled prevalence of severe hyperglycaemia, hypertension, weight gain and hyperlipidaemia within the corticosteroid arms was 5% (95% CI 2% to 9%), 6% (95% CI 4% to 8%), 13% (95% CI 8% to 18%), 8% (95% CI 4% to 17%), respectively. CST was significantly associated hyperglycaemia, hypertension and weight gain as noted in double-blinded placebo-controlled parallel-arms studies: OR of 2.13 (95% CI 1.66 to 2.72), 1.68 (95% CI 0.96 to 2.95) and 5.20 (95% CI 2.10 to 12.90), respectively. Intravenous therapy posed higher risk than oral therapy: OR of 2.39 (95% CI 1.16 to 4.91).Limitations There was significant heterogeneity in the AE definitions and quality of AE reporting in the primary studies and patient populations in the studies. The impact of cumulative dose effect on incidental AE could not be calculated.Conclusions and implications of key findings Systemic CST use is associated with increased risk of metabolic AEs, which differs for each disease group and route of administration.PROSPERO registration number CRD42020161270.https://bmjopen.bmj.com/content/12/12/e061476.full
spellingShingle Szilard Nemes
Veronica Phillips
Spoorthy Kulkarni
Hannah Durham
Luke Glover
Osaid Ather
Leslie Cousens
Parmis Blomgran
Philip Ambery
Metabolic adverse events associated with systemic corticosteroid therapy—a systematic review and meta-analysis
title Metabolic adverse events associated with systemic corticosteroid therapy—a systematic review and meta-analysis
title_full Metabolic adverse events associated with systemic corticosteroid therapy—a systematic review and meta-analysis
title_fullStr Metabolic adverse events associated with systemic corticosteroid therapy—a systematic review and meta-analysis
title_full_unstemmed Metabolic adverse events associated with systemic corticosteroid therapy—a systematic review and meta-analysis
title_short Metabolic adverse events associated with systemic corticosteroid therapy—a systematic review and meta-analysis
title_sort metabolic adverse events associated with systemic corticosteroid therapy a systematic review and meta analysis
url https://bmjopen.bmj.com/content/12/12/e061476.full
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