Skip to main content
Top
Published in: Arthritis Research & Therapy 1/2019

Open Access 01-12-2019 | Knee Osteoarthritis | Research article

Association between metformin use and disease progression in obese people with knee osteoarthritis: data from the Osteoarthritis Initiative—a prospective cohort study

Authors: Yuanyuan Wang, Sultana Monira Hussain, Anita E. Wluka, Yuan Z. Lim, François Abram, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Flavia M. Cicuttini

Published in: Arthritis Research & Therapy | Issue 1/2019

Login to get access

Abstract

Objective

To examine whether metformin use was associated with knee cartilage volume loss over 4 years and risk of total knee replacement over 6 years in obese individuals with knee osteoarthritis.

Methods

This study analysed the Osteoarthritis Initiative participants with radiographic knee osteoarthritis (Kellgren-Lawrence grade ≥ 2) who were obese (body mass index [BMI] ≥ 30 kg/m2). Participants were classified as metformin users if they self-reported regular metformin use at baseline, 1-year and 2-year follow-up (n = 56). Non-users of metformin were defined as participants who did not report the use of metformin at any visit from baseline to 4-year follow-up (n = 762). Medial and lateral cartilage volume (femoral condyle and tibial plateau) were assessed using magnetic resonance imaging at baseline and 4 years. Total knee replacement over 6 years was assessed. General linear model and binary logistic regression were used for statistical analyses.

Results

The rate of medial cartilage volume loss was lower in metformin users compared with non-users (0.71% vs. 1.57% per annum), with a difference of − 0.86% per annum (95% CI − 1.58% to − 0.15%, p = 0.02), after adjustment for age, gender, BMI, pain score, Kellgren-Lawrence grade, self-reported diabetes, and weight change over 4 years. Metformin use was associated with a trend towards a significant reduction in risk of total knee replacement over 6 years (odds ratio 0.30, 95% CI 0.07–1.30, p = 0.11), after adjustment for age, gender, BMI, Kellgren-Lawrence grade, pain score, and self-reported diabetes.

Conclusions

These data suggest that metformin use may have a beneficial effect on long-term knee joint outcomes in those with knee osteoarthritis and obesity. Randomised controlled trials are needed to confirm these findings and determine whether metformin would be a potential disease-modifying drug for knee osteoarthritis with the obese phenotype.
Literature
1.
go back to reference GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016, 388:1545–1602. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016, 388:1545–1602.
2.
go back to reference van der Esch M, Knoop J, van der Leeden M, Roorda LD, Lems WF, Knol DL, Dekker J. Clinical phenotypes in patients with knee osteoarthritis: a study in the Amsterdam osteoarthritis cohort. Osteoarthr Cartil. 2015;23:544–9.CrossRefPubMed van der Esch M, Knoop J, van der Leeden M, Roorda LD, Lems WF, Knol DL, Dekker J. Clinical phenotypes in patients with knee osteoarthritis: a study in the Amsterdam osteoarthritis cohort. Osteoarthr Cartil. 2015;23:544–9.CrossRefPubMed
3.
go back to reference Knoop J, van der Leeden M, Thorstensson CA, Roorda LD, Lems WF, Knol DL, Steultjens MP, Dekker J. Identification of phenotypes with different clinical outcomes in knee osteoarthritis: data from the osteoarthritis initiative. Arthritis Care Res (Hoboken). 2011;63:1535–42.CrossRef Knoop J, van der Leeden M, Thorstensson CA, Roorda LD, Lems WF, Knol DL, Steultjens MP, Dekker J. Identification of phenotypes with different clinical outcomes in knee osteoarthritis: data from the osteoarthritis initiative. Arthritis Care Res (Hoboken). 2011;63:1535–42.CrossRef
4.
go back to reference Thijssen E, van Caam A, van der Kraan PM. Obesity and osteoarthritis, more than just wear and tear: pivotal roles for inflamed adipose tissue and dyslipidaemia in obesity-induced osteoarthritis. Rheumatology (Oxford). 2015;54:588–600.CrossRef Thijssen E, van Caam A, van der Kraan PM. Obesity and osteoarthritis, more than just wear and tear: pivotal roles for inflamed adipose tissue and dyslipidaemia in obesity-induced osteoarthritis. Rheumatology (Oxford). 2015;54:588–600.CrossRef
5.
go back to reference Berenbaum F, Eymard F, Houard X. Osteoarthritis, inflammation and obesity. Curr Opin Rheumatol. 2013;25:114–8.CrossRefPubMed Berenbaum F, Eymard F, Houard X. Osteoarthritis, inflammation and obesity. Curr Opin Rheumatol. 2013;25:114–8.CrossRefPubMed
6.
go back to reference Puenpatom RA, Victor TW. Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data. Postgrad Med. 2009;121:9–20.CrossRefPubMed Puenpatom RA, Victor TW. Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data. Postgrad Med. 2009;121:9–20.CrossRefPubMed
7.
go back to reference Dawson LP, Fairley JL, Papandony MC, Hussain SM, Cicuttini FM, Wluka AE. Is abnormal glucose tolerance or diabetes a risk factor for knee, hip, or hand osteoarthritis? A systematic review. Semin Arthritis Rheum. 2018;48:176–89.CrossRefPubMed Dawson LP, Fairley JL, Papandony MC, Hussain SM, Cicuttini FM, Wluka AE. Is abnormal glucose tolerance or diabetes a risk factor for knee, hip, or hand osteoarthritis? A systematic review. Semin Arthritis Rheum. 2018;48:176–89.CrossRefPubMed
8.
go back to reference Saisho Y. Metformin and inflammation: its potential beyond glucose-lowering effect. Endocr Metab Immune Disord Drug Targets. 2015;15:196–205.CrossRefPubMed Saisho Y. Metformin and inflammation: its potential beyond glucose-lowering effect. Endocr Metab Immune Disord Drug Targets. 2015;15:196–205.CrossRefPubMed
9.
go back to reference Mohammed MM, Al-Shamma K, Jasim NA. Evaluation of the anti-inflammatory effect of metformin as adjuvant therapy to NSAID (meloxicam) in patients with knee osteoarthritis. Int J Sci Nature. 2014;5:277–82. Mohammed MM, Al-Shamma K, Jasim NA. Evaluation of the anti-inflammatory effect of metformin as adjuvant therapy to NSAID (meloxicam) in patients with knee osteoarthritis. Int J Sci Nature. 2014;5:277–82.
10.
go back to reference Mohammed MM, Al-Shamma KJ, Jassim NA. Evaluation of the clinical use of metformin or pioglitazone in combination with meloxicam in patients with knee osteoarthritis; using knee injury and osteoarthritis outcome score. Iraqi J Pharm Sci. 2014;23:13–23. Mohammed MM, Al-Shamma KJ, Jassim NA. Evaluation of the clinical use of metformin or pioglitazone in combination with meloxicam in patients with knee osteoarthritis; using knee injury and osteoarthritis outcome score. Iraqi J Pharm Sci. 2014;23:13–23.
11.
go back to reference Lu CH, Chung CH, Lee CH, Hsieh CH, Hung YJ, Lin FH, Tsao CH, Hsieh PS, Chien WC. Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: a nationwide, retrospective, matched-cohort study in Taiwan. PLoS One. 2018;13:e0191242.CrossRefPubMedPubMedCentral Lu CH, Chung CH, Lee CH, Hsieh CH, Hung YJ, Lin FH, Tsao CH, Hsieh PS, Chien WC. Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: a nationwide, retrospective, matched-cohort study in Taiwan. PLoS One. 2018;13:e0191242.CrossRefPubMedPubMedCentral
12.
go back to reference Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15:1833–40.PubMed Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15:1833–40.PubMed
13.
go back to reference Dodin P, Pelletier JP, Martel-Pelletier J, Abram F. Automatic human knee cartilage segmentation from 3D magnetic resonance images. IEEE Trans Biomed Eng. 2010;57:2699–711.CrossRef Dodin P, Pelletier JP, Martel-Pelletier J, Abram F. Automatic human knee cartilage segmentation from 3D magnetic resonance images. IEEE Trans Biomed Eng. 2010;57:2699–711.CrossRef
14.
go back to reference Barnett LA, Jordan KP, Edwards JJ, van der Windt DA. Does metformin protect against osteoarthritis? An electronic health record cohort study. Prim Health Care Res Dev. 2017;18:623–8.CrossRefPubMed Barnett LA, Jordan KP, Edwards JJ, van der Windt DA. Does metformin protect against osteoarthritis? An electronic health record cohort study. Prim Health Care Res Dev. 2017;18:623–8.CrossRefPubMed
15.
go back to reference Pelletier JP, Cooper C, Peterfy C, Reginster JY, Brandi ML, Bruyere O, Chapurlat R, Cicuttini F, Conaghan PG, Doherty M, et al. What is the predictive value of MRI for the occurrence of knee replacement surgery in knee osteoarthritis? Ann Rheum Dis. 2013;72:1594–604.CrossRefPubMed Pelletier JP, Cooper C, Peterfy C, Reginster JY, Brandi ML, Bruyere O, Chapurlat R, Cicuttini F, Conaghan PG, Doherty M, et al. What is the predictive value of MRI for the occurrence of knee replacement surgery in knee osteoarthritis? Ann Rheum Dis. 2013;72:1594–604.CrossRefPubMed
16.
go back to reference Kang KY, Kim YK, Yi H, Kim J, Jung HR, Kim IJ, Cho JH, Park SH, Kim HY, Ju JH. Metformin downregulates Th17 cells differentiation and attenuates murine autoimmune arthritis. Int Immunopharmacol. 2013;16:85–92.CrossRefPubMed Kang KY, Kim YK, Yi H, Kim J, Jung HR, Kim IJ, Cho JH, Park SH, Kim HY, Ju JH. Metformin downregulates Th17 cells differentiation and attenuates murine autoimmune arthritis. Int Immunopharmacol. 2013;16:85–92.CrossRefPubMed
17.
go back to reference Son HJ, Lee J, Lee SY, Kim EK, Park MJ, Kim KW, Park SH, Cho ML. Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis. Mediat Inflamm. 2014;2014:973986.CrossRef Son HJ, Lee J, Lee SY, Kim EK, Park MJ, Kim KW, Park SH, Cho ML. Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis. Mediat Inflamm. 2014;2014:973986.CrossRef
18.
go back to reference Stannus O, Jones G, Cicuttini F, Parameswaran V, Quinn S, Burgess J, Ding C. Circulating levels of IL-6 and TNF-alpha are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults. Osteoarthr Cartil. 2010;18:1441–7.CrossRefPubMed Stannus O, Jones G, Cicuttini F, Parameswaran V, Quinn S, Burgess J, Ding C. Circulating levels of IL-6 and TNF-alpha are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults. Osteoarthr Cartil. 2010;18:1441–7.CrossRefPubMed
19.
go back to reference Davies-Tuck ML, Wang Y, Wluka AE, Berry PA, Giles GG, English DR, Cicuttini FM. Increased fasting serum glucose concentration is associated with adverse knee structural changes in adults with no knee symptoms and diabetes. Maturitas. 2012;72:373–8.CrossRefPubMed Davies-Tuck ML, Wang Y, Wluka AE, Berry PA, Giles GG, English DR, Cicuttini FM. Increased fasting serum glucose concentration is associated with adverse knee structural changes in adults with no knee symptoms and diabetes. Maturitas. 2012;72:373–8.CrossRefPubMed
20.
go back to reference Davies-Tuck ML, Hanna F, Davis SR, Bell RJ, Davison SL, Wluka AE, Adams J, Cicuttini FM. Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women - a prospective cohort study. Arthritis Res Ther. 2009;11:R181.CrossRefPubMedPubMedCentral Davies-Tuck ML, Hanna F, Davis SR, Bell RJ, Davison SL, Wluka AE, Adams J, Cicuttini FM. Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women - a prospective cohort study. Arthritis Res Ther. 2009;11:R181.CrossRefPubMedPubMedCentral
Metadata
Title
Association between metformin use and disease progression in obese people with knee osteoarthritis: data from the Osteoarthritis Initiative—a prospective cohort study
Authors
Yuanyuan Wang
Sultana Monira Hussain
Anita E. Wluka
Yuan Z. Lim
François Abram
Jean-Pierre Pelletier
Johanne Martel-Pelletier
Flavia M. Cicuttini
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2019
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-019-1915-x

Other articles of this Issue 1/2019

Arthritis Research & Therapy 1/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.