Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 26, 2021; 9(33): 10198-10207
Published online Nov 26, 2021. doi: 10.12998/wjcc.v9.i33.10198
Impacts of statin and metformin on neuropathy in patients with type 2 diabetes mellitus: Korean Health Insurance data
Hong Ki Min, Se Hee Kim, Jong Han Choi, Kyomin Choi, Hae-Rim Kim, Sang-Heon Lee
Hong Ki Min, Se Hee Kim, Jong Han Choi, Department of Internal Medicine, Konkuk University Medical Center, Seoul KS013, South Korea
Kyomin Choi, Department of Neurology, Konkuk University Medical Center, Seoul KS013, South Korea
Hae-Rim Kim, Sang-Heon Lee, Division of Rheumatology, Department of Internal Medicine, Konkuk University School of Medicine, Seoul KS013, South Korea
Author contributions: Min HK and Kim SH designed the research study; Min HK, Kim SH, Choi JH, Choi K and Kim HR performed the research; Min HK contributed analytic tools; Min HK analyzed the data and wrote the manuscript; all authors have read and approve the final manuscript.
Supported by the Konkuk University Medical Center Research Grant 2020.
Institutional review board statement: This study was approved by the Institutional Review Board of Konkuk University Medical Center (approval number: 2021-01-004).
Informed consent statement: The HIRA database is accessible to all researchers and holds anonymized patient information to protect the privacy of individuals. The HIRA database can be accessed by any researchers whose study protocols have been approved by an official review committee, and Informed consent of HIRA data is omitted. Therefore, written informed consent for enrollment was waived because the data were provided by HIRA.
Conflict-of-interest statement: The authors have no potential conflicts of interest to disclose.
Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sang-Heon Lee, MD, Professor, Division of Rheumatology, Department of Internal Medicine, Konkuk University School of Medicine, 120 Neung-dong Ro, Gwangjin-gu, Seoul KS013, South Korea. shlee@kuh.ac.kr
Received: July 9, 2021
Peer-review started: July 9, 2021
First decision: August 8, 2021
Revised: August 9, 2021
Accepted: September 10, 2021
Article in press: September 10, 2021
Published online: November 26, 2021
Abstract
BACKGROUND

Neuropathy is a common chronic complication in type 2 diabetes mellitus (T2DM). Statin and metformin are commonly used medications in T2DM patients, and some studies showed statin- or metformin-induced neuropathy.

AIM

To evaluate the incidence of neuropathy among patients with T2DM associated with statin and metformin therapies.

METHODS

Korean Health Insurance Review and Assessment national patient sample data from 2016 and 2017 were used. Patients with T2DM and no complications were divided into statin/metformin/statin + metformin users and non-users. Neuropathy incidence was defined by International Statistical Classification of Diseases and Related Health Problems, 10th revision codes and concomitant prescriptions for anticonvulsants or antidepressants. Logistic regression analyses were conducted to examine the associations between statin/metformin/statin + metformin therapies and the incidence of neuropathy. Propensity score (PS) matching was performed on the basis of age, sex and comorbidities.

RESULTS

Overall, 34964 and 35887 patients with T2DM and no complications were included in the Korean Health Insurance Review and Assessment national patient sample datasets from 2016 and 2017, respectively. Statin therapy was associated with increased risks of neuropathy in 2016 and 2017 [PS-matched odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.08-1.38; PS-matched OR = 1.17, 95%CI: 1.03-1.33, respectively]. Metformin therapy was associated with reduced risks of neuropathy in 2016 and 2017 (PS-matched OR = 0.30, 95%CI: 0.21-0.42; PS-matched OR = 0.44, 95%CI: 0.32-0.60, respectively). Combined statin + metformin therapy was not significantly associated with neuropathy in 2016 or 2017 (PS-matched OR = 0.85, 95%CI: 0.61-1.19; PS-matched OR = 0.95, 95%CI: 0.66-1.38, respectively).

CONCLUSION

Statin therapy was associated with enhanced risk of new-onset neuropathy in patients with T2DM, but metformin therapy showed the opposite association.

Keywords: Diabetes mellitus, Neuropathies, Hydroxymethylglutaryl-CoA reductase inhibitors, Metformin

Core Tip: Diabetic neuropathy is one of the most common chronic complications in patients with type 2 diabetes mellitus. Statin is a commonly used lipid lowering agent in patients with type 2 diabetes mellitus, and metformin is background medication for type 2 diabetes mellitus. In some observational studies, statin and metformin were associated with an increased risk of neuropathy. In the present study using Korean Health Insurance Review and Assessment national patient sample data, the use of statin was associated with increased risk of diabetic neuropathy occurrence, whereas metformin use showed a negative association with diabetic neuropathy.