Risk of Lactic Acidosis in Hospitalized Diabetic Patients Prescribed Biguanides in Japan: A Retrospective Total-Population Cohort Study

Takako Mohri; Sawako Okamoto; Yuichi Nishioka; Tomoya Myojin; Shinichiro Kubo; Tsuneyuki Higashino; Sadanori Okada; Yasuhiro Akai; Tatsuya Noda; Hitoshi Ishii; Tomoaki Imamura

doi:10.3390/ijerph20075300

Risk of Lactic Acidosis in Hospitalized Diabetic Patients Prescribed Biguanides in Japan: A Retrospective Total-Population Cohort Study

Int J Environ Res Public Health. 2023 Mar 29;20(7):5300. doi: 10.3390/ijerph20075300.

Authors

Affiliations

¹ Department of Diabetes and Endocrinology, Nara Medical University Hospital, Nara 634-8522, Japan.
² Department of Public Health, Health Management and Policy, Nara Medical University, Nara 634-8521, Japan.
³ Education Development Center, Nara Medical University, Nara 634-8521, Japan.
⁴ Healthcare and Wellness Division, Mitsubishi Research Institute Inc., Tokyo 100-8141, Japan.
⁵ Department of Community-Based Medicine, Nara Medical University, Nara 634-8521, Japan.
⁶ Department of Doctor-Patient Relationships, Nara Medical University, Nara 634-8521, Japan.

Abstract

Patient data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) are used to assess the effect of biguanide administration on rates of lactic acidosis (LA) in hospitalized diabetes mellitus (DM) patients. In this retrospective cohort study (from April 2013 to March 2016), we compare DM inpatients prescribed biguanides to DM inpatients who were not prescribed biguanides to quantify the association between biguanides and incidence of LA. In total, 8,111,848 DM patient records are retrieved from the NDB. Of the 528,768 inpatients prescribed biguanides, 782 develop LA. Of the 1,967,982 inpatients not prescribed biguanides, 1310 develop LA. The rate ratio of inpatients who develop LA and are administered biguanides to those who developed LA without receiving biguanides is 1.44 (95% CI, 1.32-1.58). Incidence rates and rate ratios for both sexes are elevated in the group prescribed biguanides for patients aged 70 years and older, markedly in those 80 years and older: 40.12 and 6.31 (95% CI, 4.75-8.39), respectively, for men and 34.96 and 5.40 (95% CI, 3.91-7.46), respectively, for women. Biguanides should be used conservatively in patients older than 70 years, particularly for those with comorbidities, and with caution in patients 80 years and older.

Keywords: biguanides; diabetes mellitus; lactic acidosis; population-based database; retrospective cohort study.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acidosis, Lactic* / chemically induced
Acidosis, Lactic* / epidemiology
Aged
Aged, 80 and over
Biguanides / therapeutic use
Cohort Studies
Diabetes Mellitus* / chemically induced
Diabetes Mellitus* / drug therapy
Diabetes Mellitus* / epidemiology
Female
Humans
Inpatients
Japan / epidemiology
Male
Metformin* / adverse effects
Retrospective Studies

Substances

Biguanides
Metformin

Grants and funding

This research was funded by a grant from the Japan Agency for Medical Research and Development (AMED) (Grant Number: JP16K1310001h0001), Health Science and Labor Research Grants (HSLRG) (Grant Number: H30-Iryou-Ippan-013) of the Ministry of Health, Labour and Welfare, and the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI): Grant Numbers JP18H04126, JP20H00623, and JP18K17390.