Metformin discontinuation in patients beginning second-line glucose-lowering therapy: results from the global observational DISCOVER study programme

Objectives To evaluate the extent to which patients with type 2 diabetes discontinue metformin therapy when initiating second-line treatment and factors associated with metformin discontinuation, using baseline data from the DISCOVER study programme.Design DISCOVER is a 3-year, prospective, observat...

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Main Authors: Peter Fenici, Niklas Hammar, Linong Ji, Fengming Tang, Hirotaka Watada, Antonio Nicolucci, Wolfgang Rathmann, Iichiro Shimomura, Marilia B Gomes, Mikhail Kosiborod, Stuart Pocock, Marina V Shestakova, Hungta Chen, Javier Cid-Ruzafa
Format: Article
Language:English
Published: BMJ Publishing Group 2020-08-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/10/8/e034613.full
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author Peter Fenici
Niklas Hammar
Linong Ji
Fengming Tang
Hirotaka Watada
Antonio Nicolucci
Wolfgang Rathmann
Iichiro Shimomura
Marilia B Gomes
Mikhail Kosiborod
Stuart Pocock
Marina V Shestakova
Hungta Chen
Javier Cid-Ruzafa
author_facet Peter Fenici
Niklas Hammar
Linong Ji
Fengming Tang
Hirotaka Watada
Antonio Nicolucci
Wolfgang Rathmann
Iichiro Shimomura
Marilia B Gomes
Mikhail Kosiborod
Stuart Pocock
Marina V Shestakova
Hungta Chen
Javier Cid-Ruzafa
author_sort Peter Fenici
collection DOAJ
description Objectives To evaluate the extent to which patients with type 2 diabetes discontinue metformin therapy when initiating second-line treatment and factors associated with metformin discontinuation, using baseline data from the DISCOVER study programme.Design DISCOVER is a 3-year, prospective, observational study programme including data from 38 countries across 6 continents from 2014 to 2019.Setting Primary and secondary healthcare centres, hospitals and specialist diabetes centres in both urban and rural locations.Participants A total of 15 992 patients with type 2 diabetes initiating second-line glucose-lowering therapy.Primary and secondary outcome measures The proportion of patients who discontinued metformin as a second-line therapy and the factors associated with this treatment change.Results Of the 14 668 patients (from 37 countries) with valid treatment data, 11 837 (80.7%) received metformin as first-line glucose-lowering therapy; 8488 (71.7%) received metformin monotherapy and 3349 (28.3%) received metformin as part of a combination therapy. Overall, treatment with metformin was discontinued in 15.1% (1782) of patients who received first-line metformin (14.1% (1194) and 17.6% (588) in those who received metformin as monotherapy and as part of a combination, respectively); this proportion varied across regions from 6.9% (54) in Africa to 20.6% (628) in South-East Asia. On metformin discontinuation, 73.6% (1311) of patients received a non-insulin monotherapy at second line. Factors associated with an increased odds of metformin discontinuation were older age (≥75 years) and having a history of chronic kidney disease. The probability of metformin monotherapy discontinuation was lower in patients from Africa than in those from Europe.Conclusions A substantial number of patients discontinued taking metformin when beginning second-line therapy. Most of these patients subsequently received a non-insulin monotherapy at second line, in contradiction to international guidelines and potentially leaving them at an increased risk of hyperglycaemia and associated adverse outcomes.Trial registration numbers NCT02322762 and NCT02226822.
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spelling doaj-art-3fa27abaed344ef894964068e1189e222025-08-20T02:38:55ZengBMJ Publishing GroupBMJ Open2044-60552020-08-0110810.1136/bmjopen-2019-034613Metformin discontinuation in patients beginning second-line glucose-lowering therapy: results from the global observational DISCOVER study programmePeter Fenici0Niklas Hammar1Linong Ji2Fengming Tang3Hirotaka Watada4Antonio Nicolucci5Wolfgang Rathmann6Iichiro Shimomura7Marilia B Gomes8Mikhail Kosiborod9Stuart Pocock10Marina V Shestakova11Hungta Chen12Javier Cid-Ruzafa13AstraZeneca, Cambridge, UK2 Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, ChinaDepartment of Cardiovascular research, Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, USAJuntendo University School of Medicine Graduate School of Medicine, Bunkyo-ku, JapandiabetologistInstitute for Biometrics and Epidemiology, German Diabetes Center Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Dusseldorf, GermanyMetabolic Medicine, Osaka University Graduate School of Medicine Faculty of Medicine Division of Medicine, Suita, Osaka, JapanDepartment of Internal Medicine, Rio de Janeiro State University, Rio de Janeiro, RJ, BrazilDepartment of Internal Medicine, University of Missouri Kansas City, Kansas City, Missouri, USADepartment of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UKFeberal Scientific Centre of Endocrinology, Endocrinology Research Centre, Moscow, Russian FederationMedical/Payer Evidence Statistics, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Maryland, USAEvidera, Barcelona, SpainObjectives To evaluate the extent to which patients with type 2 diabetes discontinue metformin therapy when initiating second-line treatment and factors associated with metformin discontinuation, using baseline data from the DISCOVER study programme.Design DISCOVER is a 3-year, prospective, observational study programme including data from 38 countries across 6 continents from 2014 to 2019.Setting Primary and secondary healthcare centres, hospitals and specialist diabetes centres in both urban and rural locations.Participants A total of 15 992 patients with type 2 diabetes initiating second-line glucose-lowering therapy.Primary and secondary outcome measures The proportion of patients who discontinued metformin as a second-line therapy and the factors associated with this treatment change.Results Of the 14 668 patients (from 37 countries) with valid treatment data, 11 837 (80.7%) received metformin as first-line glucose-lowering therapy; 8488 (71.7%) received metformin monotherapy and 3349 (28.3%) received metformin as part of a combination therapy. Overall, treatment with metformin was discontinued in 15.1% (1782) of patients who received first-line metformin (14.1% (1194) and 17.6% (588) in those who received metformin as monotherapy and as part of a combination, respectively); this proportion varied across regions from 6.9% (54) in Africa to 20.6% (628) in South-East Asia. On metformin discontinuation, 73.6% (1311) of patients received a non-insulin monotherapy at second line. Factors associated with an increased odds of metformin discontinuation were older age (≥75 years) and having a history of chronic kidney disease. The probability of metformin monotherapy discontinuation was lower in patients from Africa than in those from Europe.Conclusions A substantial number of patients discontinued taking metformin when beginning second-line therapy. Most of these patients subsequently received a non-insulin monotherapy at second line, in contradiction to international guidelines and potentially leaving them at an increased risk of hyperglycaemia and associated adverse outcomes.Trial registration numbers NCT02322762 and NCT02226822.https://bmjopen.bmj.com/content/10/8/e034613.full
spellingShingle Peter Fenici
Niklas Hammar
Linong Ji
Fengming Tang
Hirotaka Watada
Antonio Nicolucci
Wolfgang Rathmann
Iichiro Shimomura
Marilia B Gomes
Mikhail Kosiborod
Stuart Pocock
Marina V Shestakova
Hungta Chen
Javier Cid-Ruzafa
Metformin discontinuation in patients beginning second-line glucose-lowering therapy: results from the global observational DISCOVER study programme
BMJ Open
title Metformin discontinuation in patients beginning second-line glucose-lowering therapy: results from the global observational DISCOVER study programme
title_full Metformin discontinuation in patients beginning second-line glucose-lowering therapy: results from the global observational DISCOVER study programme
title_fullStr Metformin discontinuation in patients beginning second-line glucose-lowering therapy: results from the global observational DISCOVER study programme
title_full_unstemmed Metformin discontinuation in patients beginning second-line glucose-lowering therapy: results from the global observational DISCOVER study programme
title_short Metformin discontinuation in patients beginning second-line glucose-lowering therapy: results from the global observational DISCOVER study programme
title_sort metformin discontinuation in patients beginning second line glucose lowering therapy results from the global observational discover study programme
url https://bmjopen.bmj.com/content/10/8/e034613.full
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