Skip to main content
SpringerLink
Log in

Appraisal of guidelines for managing contrast medium in patients with metformin: consensuses, controversies, and gaps

  • Cardiac
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

The current guidelines contain substantial inconsistency regarding the use of metformin concomitantly with contrast media. The objective of this study is to appraise the guidelines and summarize the agreements and differences among recommendations.

Methods

Our search focused on English language guidelines published between 2018 and 2021. Guidelines for the management of contrast media in patients with continuous metformin were included. Guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation II instrument.

Results

Six guidelines out of 1134 fulfilled the inclusion criteria with an AGREE II score of 79.2% (IQR 72.7 to 85.1%). There was good overall quality of the guidelines, with six considered “strongly recommended.” CPGs scored poorly in “Clarity of Presentation” and “Applicability,” with scores of 75.9% and 76.4%, respectively. The intraclass correlation coefficients were excellent in each domain. There are some guidelines (33.3%) that recommend discontinuation of metformin in patients with an eGFR of < 30 mL/min/1.73 m2, while some guidelines (16.7%) suggest the threshold of renal function should be eGFR < 40 mL/min/1.73 m2.

Conclusions

Most guidelines recommend withdrawing metformin before using contrast agents in diabetic patients with severely impaired kidney function but disagree on the renal function thresholds. Furthermore, the gaps regarding discontinuing metformin with moderate renal impairment (30 mL/min/1.73 m2 < eGFR < 60 mL/min/1.73 m2) must be considered in future studies.

Key Points

• Guidelines involving metformin and contrast agents are reliable and optimal.

• Most guidelines advocate discontinuing metformin before using contrast agents in diabetic patients with advanced renal failure, but there are controversial suggestions regarding kidney function thresholds.

• The gaps regarding the time of discontinuation of the metformin with moderate renal impairment (30 mL/min/1.73 m2 < eGFR < 60 mL/min/1.73 m2) must be considered in the extensive RCT studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

ACR:

American College of Radiology

CA:

Coronary angiography

CAD:

Coronary artery disease

CAR:

Canadian Association of Radiologists

CI-AKI:

Contrast-induced acute kidney injury

CKD:

Chronic kidney disease

COI:

Conflict of interest

CPGs:

Clinical practice guidelines

EACTS:

European Association for Cardio-Thoracic Surgery

EASD:

European Association for the Study of Diabetes

ESC:

The European Society of Cardiology

ESUR:

European Society of Urogenital Radiology

ICC:

Intraclass correlation

ICM:

Iodinated contrast media

JCS:

Japanese Circulation Society

JRS:

Japan Radiological Society

JSN:

Japanese Society of Nephrology

MALA:

Metformin-associated lactic acidosis

PCI:

Percutaneous coronary intervention

RANZCR:

Royal Australian and New Zealand College of Radiologists

RCR:

Royal College of Radiologists

RCTs:

Randomized controlled trials

RSTN:

Radiological Society of the Netherlands

sCr:

Serum creatinine

References

  1. Bashier A , Hussain AB, Abdelgadir E, Alawadi F, Sabbour H, Chilton R (2019) Consensus recommendations for management of patients with type 2 diabetes mellitus and cardiovascular diseases. Diabetol Metab Syndr 11:80

  2. Maruthur NM, Tseng E, Hutfless S et al (2016) Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 164:740

  3. 2019 ESC Guidelines on diabetes (2020) pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). Rev Esp Cardiol Engl Ed 73:404

    Google Scholar 

  4. Posma RA, Lexis CHP, Lipsic E et al (2015) Effect of metformin on renal function after primary percutaneous coronary intervention in patients without diabetes presenting with ST-elevation myocardial infarction: data from the GIPS-III trial. Cardiovasc Drugs Ther 29:451–459

  5. Fähling M, Seeliger E, Patzak A, Persson PB (2017) Understanding and preventing contrast-induced acute kidney injury. Nat Rev Nephrol 13:169–180

    Article  PubMed  Google Scholar 

  6. van der Molen AJ, Reimer P, Dekkers IA et al (2018) Post-contrast acute kidney injury. Part 2: risk stratification, role of hydration and other prophylactic measures, patients taking metformin and chronic dialysis patients. Eur Radiol 28:2856–2869

  7. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK (2014) Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA 312:2668–2675

    Article  PubMed  PubMed Central  Google Scholar 

  8. Fan Y, Zhang G, Zhang Z et al (2022) Critical appraisal of guidelines for antithrombotic therapy in atrial fibrillation post-percutaneous coronary intervention. Glob Heart 17:14

  9. Neumann F-J, Suosa-Uva M, Ahlsson A  et al (2018) 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 40:87–165

  10. American College of Radiology (2020) Manual on contrast media, http://www.acr.org. (American College of Radiology)

  11. Isaka Y, Hayashi H, Aonuma K et al (2019) Guideline on the use of iodinated contrast media in patients with kidney disease 2018. Jpn J Radiol 38:3–46

  12. Doyle M (2018) Iodinated Contrast Media Guideline 41:14

    Google Scholar 

  13. Mikdashi J (2022) The meaningful role of patients, and other stakeholders in clinical practice guideline development. Rheum Dis Clin N Am 48:691–703

    Article  Google Scholar 

  14. Grimshaw JM, Russell IT (2003) Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet 342:1317–1322

  15. Lancet T (2019) Managing conflicts of interests in clinical guidelines. Lancet 394:710

    Article  Google Scholar 

  16. Dyer O (2020) WHO retracts opioid guidelines after accepting that industry had an influence. BMJ 368:m105

    Article  PubMed  Google Scholar 

  17. McDonald JS, Leake CB, McDonald RJ et al (2016) Acute kidney injury after intravenous versus intra-arterial contrast material administration in a paired cohort. Invest Radiol 51(12):804–809

  18. Tong GE, Kumar S, Chong KC et al (2016) Risk of contrast-induced nephropathy for patients receiving intravenous vs. intra-arterial iodixanol administration. Abdom Radiol (NY) 41(1):91–9

    Article  PubMed  Google Scholar 

  19. Kooiman J, Le Haen PA, Gezgin G et al (2013) Contrast-induced acute kidney injury and clinical outcomes after intra-arterial and intravenous contrast administration: risk comparison adjusted for patient characteristics by design. Am Heart J. 165(5):793-99, 799.e1

  20. Karlsberg RP, Dohad SY, Sheng R (2011) Iodixanol peripheral computed tomographic angiography study investigator panel Contrast medium-induced acute kidney injury: comparison of intravenous and intraarterial administration of iodinated contrast medium. J Vasc Interv Radiol 22(8):1159–65

    Article  PubMed  Google Scholar 

  21. Kao T-W, Lee K-H, Chan WP, Fan K-C, Liu C-W, Huang Y-C (2022) Continuous use of metformin in patients receiving contrast medium: what is the evidence? A systematic review and meta-analysis. Eur Radiol 32:3045–3055

  22. Orloff J, Min JY, Mushlin A, Flory J (2021) Safety and effectiveness of metformin in patients with reduced renal function: a systematic review. Diabetes Obes Metab 23:2035–2047

    Article  CAS  PubMed  Google Scholar 

  23. Prabhu RA, Mareddy AS, Nagaraju SP, Rangaswamy D, Guddattu V (2019) Lactic acidosis due to metformin in type 2 diabetes mellitus and chronic kidney disease stage 3–5: is it significant? Int Urol Nephrol 51:1229–1230

    Article  PubMed  Google Scholar 

  24. Lee EY, Hwang S, Lee YH et al (2017) Association between metformin use and risk of lactic acidosis or elevated lactate concentration in type 2 diabetes. Yonsei Med J 58:312

  25. Lazarus B, Wu A, Shin J-I et al (2018) Association of metformin use with risk of lactic acidosis across the range of kidney function. JAMA Intern Med 178:903

  26. Misbin RI (2007) The phantom of lactic acidosis due to metformin in patients with diabetes. Diabetes Care 27:1791–1793

    Article  Google Scholar 

  27. Goergen SK, Rumbold G, Compton G, Harris C (2009) Systematic review of current guidelines, and their evidence base, on risk of lactic acidosis after administration of contrast medium for patients receiving metformin. Radiology 254:261–269

    Article  Google Scholar 

  28. Yu Q, Zhu J-J, Liu W-X (2020) Effect of continuous use of metformin on kidney function in diabetes patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. 9. https://doi.org/10.1186/s12872-020-01474-5

  29. Grimshaw JM, Russell IT (1993) Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet 342:1317–1322. https://doi.org/10.1016/0140-6736(93)92244-n

Download references

Funding

The authors state that this work has not received any funding.

Author information

Author notes

  1. Yongqiang Fan and Qingqing Cai contributed equally to the study.

Authors and Affiliations

  1. Department of Cardiology, DongGuan Tungwah Hospital, DongGuan, China

    Yongqiang Fan, Shunhua Chen & Yixun Zhang

  2. Department of Cardiology, Sun Yat-Sen University, Guangzhou, Guangdong, China

    Yongqiang Fan

  3. Department of Cardiology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, No. 23, Beijie Road, Jiangmen, 529000, Guangdong, China

    Qingqing Cai, Bin Zhang & Gaoxing Zhang

  4. Department of Cardiology, GuangDong Medical University, Zhanjiang, China

    Qingqing Cai

  5. Department of Cardiology, KaiPing Second People’s Hospital, No. 22, Shixi Road, Jiangmen, 529300, Guangdong, China

    Jinhuan Zhen

Authors
  1. Yongqiang Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qingqing Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shunhua Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yixun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jinhuan Zhen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gaoxing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jinhuan Zhen or Gaoxing Zhang.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Gaoxing Zhang.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was not required for this study.

Ethical approval

This article does not involve examinations performed on human beings or animals. Therefore, ethical approval was not necessary.

Methodology

• Appraisal using Agree-II tool

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 190 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fan, Y., Cai, Q., Chen, S. et al. Appraisal of guidelines for managing contrast medium in patients with metformin: consensuses, controversies, and gaps. Eur Radiol 33, 6290–6298 (2023). https://doi.org/10.1007/s00330-023-09611-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-023-09611-2

Keywords

Search

Navigation