Association of metformin with susceptibility to COVID-19 in people with type 2 diabetes

Jingya Wang; Jennifer M Cooper; Krishna Gokhale; Dionisio Acosta-Mena; Samir Dhalla; Nathan Byne; Joht Singh Chandan; Astha Anand; Kelvin Okoth; Anuradhaa Subramanian; Mansoor N Bangash; Thomas Jackson; Dawit Zemedikun; Tom Taverner; Wasim Hanif; Sandip Ghosh; Parth Narendran; Konstantinos A Toulis; Abd A Tahrani; Rajendra Surenthirakumaran; Nicola J Adderley; Shamil Haroon; Kamlesh Khunti; Christopher Sainsbury; G Neil Thomas; Krishnarajah Nirantharakumar

doi:10.1210/clinem/dgab067

Association of metformin with susceptibility to COVID-19 in people with type 2 diabetes

Jingya Wang, Jennifer M Cooper, Krishna Gokhale, Dionisio Acosta-Mena, Samir Dhalla, Nathan Byne, Joht Singh Chandan, Astha Anand, Kelvin Okoth, Anuradhaa Subramanian, Mansoor N Bangash, Thomas Jackson, Dawit Zemedikun, Tom Taverner, Wasim Hanif, Sandip Ghosh, Parth Narendran, Konstantinos A Toulis, Abd A Tahrani, Rajendra SurenthirakumaranNicola J Adderley, Shamil Haroon, Kamlesh Khunti, Christopher Sainsbury, G Neil Thomas, Krishnarajah Nirantharakumar

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Abstract

OBJECTIVE: Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes.

RESEARCH DESIGN AND METHODS: We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed.

RESULTS: There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding.

CONCLUSION: Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.

Original language	English
Article number	dgab067
Pages (from-to)	1255-1268
Number of pages	14
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	106
Issue number	5
Early online date	9 Feb 2021
DOIs	https://doi.org/10.1210/clinem/dgab067
Publication status	Published - May 2021

Bibliographical note

Keywords

Aged
COVID-19/complications
Cohort Studies
Diabetes Mellitus, Type 2/complications
Female
Humans
Hypoglycemic Agents/administration & dosage
Kaplan-Meier Estimate
Male
Metformin/administration & dosage
Middle Aged
Propensity Score
Retrospective Studies
SARS-CoV-2 infection
metformin
COVID-19
type 2 diabetes mellitus

ASJC Scopus subject areas

Biochemistry, medical
Endocrinology
Biochemistry
Clinical Biochemistry
Endocrinology, Diabetes and Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1210/clinem/dgab067Licence: Creative Commons: Attribution (CC BY)

WangJ2021AssociationFinal published version, 1.11 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

Wang, J., Cooper, J. M., Gokhale, K., Acosta-Mena, D., Dhalla, S., Byne, N., Chandan, J. S., Anand, A., Okoth, K., Subramanian, A., Bangash, M. N., Jackson, T., Zemedikun, D., Taverner, T., Hanif, W., Ghosh, S., Narendran, P., Toulis, K. A., Tahrani, A. A., ... Nirantharakumar, K. (2021). Association of metformin with susceptibility to COVID-19 in people with type 2 diabetes. Journal of Clinical Endocrinology and Metabolism, 106(5), 1255-1268. Article dgab067. Advance online publication. https://doi.org/10.1210/clinem/dgab067

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title = "Association of metformin with susceptibility to COVID-19 in people with type 2 diabetes",

abstract = "OBJECTIVE: Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes.RESEARCH DESIGN AND METHODS: We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed.RESULTS: There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding.CONCLUSION: Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.",

keywords = "Aged, COVID-19/complications, Cohort Studies, Diabetes Mellitus, Type 2/complications, Female, Humans, Hypoglycemic Agents/administration & dosage, Kaplan-Meier Estimate, Male, Metformin/administration & dosage, Middle Aged, Propensity Score, Retrospective Studies, SARS-CoV-2 infection, metformin, COVID-19, type 2 diabetes mellitus",

author = "Jingya Wang and Cooper, {Jennifer M} and Krishna Gokhale and Dionisio Acosta-Mena and Samir Dhalla and Nathan Byne and Chandan, {Joht Singh} and Astha Anand and Kelvin Okoth and Anuradhaa Subramanian and Bangash, {Mansoor N} and Thomas Jackson and Dawit Zemedikun and Tom Taverner and Wasim Hanif and Sandip Ghosh and Parth Narendran and Toulis, {Konstantinos A} and Tahrani, {Abd A} and Rajendra Surenthirakumaran and Adderley, {Nicola J} and Shamil Haroon and Kamlesh Khunti and Christopher Sainsbury and Thomas, {G Neil} and Krishnarajah Nirantharakumar",

note = "{\textcopyright} The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. ",

year = "2021",

month = may,

doi = "10.1210/clinem/dgab067",

language = "English",

volume = "106",

pages = "1255--1268",

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Wang, J , Cooper, JM , Gokhale, K, Acosta-Mena, D, Dhalla, S, Byne, N, Chandan, JS, Anand, A, Okoth, K, Subramanian, A, Bangash, MN, Jackson, T, Zemedikun, D, Taverner, T, Hanif, W, Ghosh, S, Narendran, P, Toulis, KA, Tahrani, AA, Surenthirakumaran, R, Adderley, NJ , Haroon, S, Khunti, K, Sainsbury, C, Thomas, GN & Nirantharakumar, K 2021, 'Association of metformin with susceptibility to COVID-19 in people with type 2 diabetes', Journal of Clinical Endocrinology and Metabolism, vol. 106, no. 5, dgab067, pp. 1255-1268. https://doi.org/10.1210/clinem/dgab067

TY - JOUR

T1 - Association of metformin with susceptibility to COVID-19 in people with type 2 diabetes

AU - Wang, Jingya

AU - Cooper, Jennifer M

AU - Gokhale, Krishna

AU - Acosta-Mena, Dionisio

AU - Dhalla, Samir

AU - Byne, Nathan

AU - Chandan, Joht Singh

AU - Anand, Astha

AU - Okoth, Kelvin

AU - Subramanian, Anuradhaa

AU - Bangash, Mansoor N

AU - Jackson, Thomas

AU - Zemedikun, Dawit

AU - Taverner, Tom

AU - Hanif, Wasim

AU - Ghosh, Sandip

AU - Narendran, Parth

AU - Toulis, Konstantinos A

AU - Tahrani, Abd A

AU - Surenthirakumaran, Rajendra

AU - Adderley, Nicola J

AU - Haroon, Shamil

AU - Khunti, Kamlesh

AU - Sainsbury, Christopher

AU - Thomas, G Neil

AU - Nirantharakumar, Krishnarajah

N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

PY - 2021/5

Y1 - 2021/5

N2 - OBJECTIVE: Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes.RESEARCH DESIGN AND METHODS: We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed.RESULTS: There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding.CONCLUSION: Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.

AB - OBJECTIVE: Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes.RESEARCH DESIGN AND METHODS: We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed.RESULTS: There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding.CONCLUSION: Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.

KW - Aged

KW - COVID-19/complications

KW - Cohort Studies

KW - Diabetes Mellitus, Type 2/complications

KW - Female

KW - Humans

KW - Hypoglycemic Agents/administration & dosage

KW - Kaplan-Meier Estimate

KW - Male

KW - Metformin/administration & dosage

KW - Middle Aged

KW - Propensity Score

KW - Retrospective Studies

KW - SARS-CoV-2 infection

KW - metformin

KW - COVID-19

KW - type 2 diabetes mellitus

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U2 - 10.1210/clinem/dgab067

DO - 10.1210/clinem/dgab067

M3 - Article

C2 - 33560344

SN - 0021-972X

VL - 106

SP - 1255

EP - 1268

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 5

M1 - dgab067

ER -

Association of metformin with susceptibility to COVID-19 in people with type 2 diabetes

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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Cite this