Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM

Objective To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.Design Federated pharmacoepidemiological evaluation in LEGEND-T2DM.Setting 10 US and seven non-US electronic health record and administrative claims databas...

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Main Authors: Rohan Khera, Jing Li, Katherine Simon, Yuan Lu, Joseph S Ross, Talita Duarte-Salles, Michael E Matheny, Harlan Krumholz, Kenneth KC Man, Carlen Reyes, Paul Nagy, Nigam Shah, Martijn J Schuemie, Daniel R Morales, Scott L DuVall, Seng Chan You, Jose D Posada, George Hripcsak, Marc A Suchard, Patrick B Ryan, Anna Ostropolets, Michael Cook, Evan Minty, Andrea Pistillo, Clair Blacketer, Arya Aminorroaya, Thomas Falconer, Nestoras Mathioudakis, Jin J Zhou, Can Yin, Kelly Li, Lovedeep Singh Dhingra, Faaizah Arshad, Mary G Bowring, Fan Bu, David A Dorr, Tina E French, Elizabeth E Hanchrow, Scott Horban, Wallis CY Lau, Yuntian Liu, Michael F McLemore, Akihiko Nishimura, Nicole Pratt, Sarah Seager, Eric YF Wan, Jianxiao Yang
Format: Article
Language:English
Published: BMJ Publishing Group 2023-10-01
Series:BMJ Medicine
Online Access:https://bmjmedicine.bmj.com/content/2/1/e000651.full
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author Rohan Khera
Jing Li
Katherine Simon
Yuan Lu
Joseph S Ross
Talita Duarte-Salles
Michael E Matheny
Harlan Krumholz
Kenneth KC Man
Carlen Reyes
Paul Nagy
Nigam Shah
Martijn J Schuemie
Daniel R Morales
Scott L DuVall
Seng Chan You
Jose D Posada
George Hripcsak
Marc A Suchard
Patrick B Ryan
Anna Ostropolets
Michael Cook
Evan Minty
Andrea Pistillo
Clair Blacketer
Arya Aminorroaya
Thomas Falconer
Nestoras Mathioudakis
Jin J Zhou
Can Yin
Kelly Li
Lovedeep Singh Dhingra
Faaizah Arshad
Mary G Bowring
Fan Bu
David A Dorr
Tina E French
Elizabeth E Hanchrow
Scott Horban
Wallis CY Lau
Yuntian Liu
Michael F McLemore
Akihiko Nishimura
Nicole Pratt
Sarah Seager
Eric YF Wan
Jianxiao Yang
author_facet Rohan Khera
Jing Li
Katherine Simon
Yuan Lu
Joseph S Ross
Talita Duarte-Salles
Michael E Matheny
Harlan Krumholz
Kenneth KC Man
Carlen Reyes
Paul Nagy
Nigam Shah
Martijn J Schuemie
Daniel R Morales
Scott L DuVall
Seng Chan You
Jose D Posada
George Hripcsak
Marc A Suchard
Patrick B Ryan
Anna Ostropolets
Michael Cook
Evan Minty
Andrea Pistillo
Clair Blacketer
Arya Aminorroaya
Thomas Falconer
Nestoras Mathioudakis
Jin J Zhou
Can Yin
Kelly Li
Lovedeep Singh Dhingra
Faaizah Arshad
Mary G Bowring
Fan Bu
David A Dorr
Tina E French
Elizabeth E Hanchrow
Scott Horban
Wallis CY Lau
Yuntian Liu
Michael F McLemore
Akihiko Nishimura
Nicole Pratt
Sarah Seager
Eric YF Wan
Jianxiao Yang
author_sort Rohan Khera
collection DOAJ
description Objective To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.Design Federated pharmacoepidemiological evaluation in LEGEND-T2DM.Setting 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021.Participants 4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments.Exposure The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort.Main outcomes measures The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated.Results 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease.Conclusions Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.
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spelling doaj-art-cd277362d5684feaa32b34690f64437c2025-08-20T03:09:42ZengBMJ Publishing GroupBMJ Medicine2754-04132023-10-012110.1136/bmjmed-2023-000651Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DMRohan Khera0Jing Li1Katherine Simon2Yuan Lu3Joseph S Ross4Talita Duarte-Salles5Michael E Matheny6Harlan Krumholz7Kenneth KC Man8Carlen Reyes9Paul Nagy10Nigam Shah11Martijn J Schuemie12Daniel R Morales13Scott L DuVall14Seng Chan You15Jose D Posada16George Hripcsak17Marc A Suchard18Patrick B Ryan19Anna Ostropolets20Michael Cook21Evan Minty22Andrea Pistillo23Clair Blacketer24Arya Aminorroaya25Thomas Falconer26Nestoras Mathioudakis27Jin J Zhou28Can Yin29Kelly Li30Lovedeep Singh Dhingra31Faaizah Arshad32Mary G Bowring33Fan Bu34David A Dorr35Tina E French36Elizabeth E Hanchrow37Scott Horban38Wallis CY Lau39Yuntian Liu40Michael F McLemore41Akihiko Nishimura42Nicole Pratt43Sarah Seager44Eric YF Wan45Jianxiao Yang46Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT, USAObstetrics & Gynaecology, The University of British Columbia, Vancouver, British Columbia, CanadaResearch, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USASection of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT, USADepartment of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USAFundació Institut Universitari per a la recerca a l`Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), IDIAP Jordi Gol, Barcelona, Catalunya, SpainTennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, USASection of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT, USAResearch Department of Practice and Policy, School of Pharmacy, University College London, London, UKFundació Institut Universitari per a la recerca a l`Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), IDIAP Jordi Gol, Barcelona, Catalunya, SpainDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USACenter for Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA, USAEpidemiology, Office of the Chief Medical Officer, Johnson & Johnson, Titusville, NJ, USADivision of Population Health and Genomics, University of Dundee, Dundee, UKVeterans Affairs Informatics and Computing Infrastructure, United States Department of Veterans Affairs, Salt Lake City, UT, USADepartment of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea (aka South Korea)Systems Engineering and Computing, School of Engineering, Universidad del Norte, Barranquilla, ColombiaDepartment of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USADepartment of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USAJohnson & Johnson LLC, Raritan, New Jersey, USADepartment of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USAJohns Hopkins University School of Medicine, Baltimore, MD, USAFaculty of Medicine, O`Brien Institute for Public Health, University of Calgary, Calgary, AB, CanadaReal-World Epidemiology Research Group, Fundació Institut Universitari per a la recerca a l`Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, SpainObservational Health Data Analytics, Janssen Research and Development, Titusville, NJ, USASection of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT, USADepartment of Biomedical Informatics, Columbia University, New York, NY, USADivision of Endocrinology, Diabetes, and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USAData Transformation, Analytics, and Artificial Intelligence, Real World Solutions, IQVIA Inc, Durham, NC, USADepartment of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USASection of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT, USADepartment of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USAJohns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USADepartment of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University School of Medicine, Portland, OR, USATennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, USATennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, USADivision of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UKResearch Department of Practice and Policy, School of Pharmacy, University College London, London, UKSection of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, CT, USATennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, USADepartment of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USAQuality Use of Medicines and Pharmacy Research Centre, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA, AustraliaData Transformation, Analytics, and Artificial Intelligence, Real World Solutions, IQVIA Inc, Durham, NC, USACentre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, ChinaDepartment of Computational Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USAObjective To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.Design Federated pharmacoepidemiological evaluation in LEGEND-T2DM.Setting 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021.Participants 4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments.Exposure The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort.Main outcomes measures The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated.Results 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease.Conclusions Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.https://bmjmedicine.bmj.com/content/2/1/e000651.full
spellingShingle Rohan Khera
Jing Li
Katherine Simon
Yuan Lu
Joseph S Ross
Talita Duarte-Salles
Michael E Matheny
Harlan Krumholz
Kenneth KC Man
Carlen Reyes
Paul Nagy
Nigam Shah
Martijn J Schuemie
Daniel R Morales
Scott L DuVall
Seng Chan You
Jose D Posada
George Hripcsak
Marc A Suchard
Patrick B Ryan
Anna Ostropolets
Michael Cook
Evan Minty
Andrea Pistillo
Clair Blacketer
Arya Aminorroaya
Thomas Falconer
Nestoras Mathioudakis
Jin J Zhou
Can Yin
Kelly Li
Lovedeep Singh Dhingra
Faaizah Arshad
Mary G Bowring
Fan Bu
David A Dorr
Tina E French
Elizabeth E Hanchrow
Scott Horban
Wallis CY Lau
Yuntian Liu
Michael F McLemore
Akihiko Nishimura
Nicole Pratt
Sarah Seager
Eric YF Wan
Jianxiao Yang
Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM
BMJ Medicine
title Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM
title_full Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM
title_fullStr Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM
title_full_unstemmed Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM
title_short Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM
title_sort multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups federated pharmacoepidemiological evaluation in legend t2dm
url https://bmjmedicine.bmj.com/content/2/1/e000651.full
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