Evidence map›Paper›PMID 42730863›Full record

ArticleClinical drug investigation2026

Dose-Dependent Association of Long-Term Metformin Use and Diabetic Nephropathy Risk in Patients with Type 2 Diabetes Mellitus: A Nationwide Population-Based Study in Taiwan.

Kuang-Hua Huang, Shuo-Yan Gau, Yu-Chia Chang, Zong-Han Lin, Tung-Han Tsai, Ya-Lan Chang, Chien-Ying Lee

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Article in Clinical drug investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Kuang-Hua Huang *Department of Health Services Administration, China Medical University, Taichung, Taiwan.
Shuo-Yan Gau *Department of Medical Education, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
Yu-Chia ChangDepartment of Long Term Care, College of Health and Nursing, National Quemoy University, Kinmen, Taiwan.
Zong-Han LinSchool of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Tung-Han TsaiDepartment of Health Services Administration, China Medical University, Taichung, Taiwan.
Ya-Lan Chang *Department of Pharmacology, Chung Shan Medical University, No.110, Sec.1, Jianguo N. Rd., Taichung, 40201, Taiwan.
Chien-Ying Lee *Department of Pharmacology, Chung Shan Medical University, No.110, Sec.1, Jianguo N. Rd., Taichung, 40201, Taiwan. cshd015@csmu.edu.tw.ORCID http://orcid.org/0000-0001-8159-4645

Funding

China Medical University, Taiwan CMU114-ASIA-15Chung Shan Medical University Hospital CSH-2023-C-003Chung Shan Medical University Hospital CSH-2024-C-002Chung Shan Medical University Hospital CSH-2025-C-003
6 · The paper itself

Abstract

backgroundDiabetic nephropathy (DN) is one of the most serious chronic microvascular complications of diabetes. Animal and clinical studies on the renoprotective effects of metformin have reported inconsistent results.

objectiveThis study investigated the relationship between long-term metformin use and DN risk in patients with type 2 diabetes mellitus (T2DM), to determine whether this relationship exhibits a dose-dependent pattern.

methodsThis was a retrospective cohort study using data from a nationally representative database in Taiwan. Patients given a diagnosis of new-onset T2DM between 2002 and 2013 were divided into 2 groups: metformin and sulfonylurea treatment. We evaluated DN risk after a 5-year follow-up period. Using the Cox proportional hazard model, we estimated DN risk in correlation with the cumulative defined daily dose (cDDDs) of metformin, with adjustment for sex, age, income, urbanization level, diabetes severity, and various comorbidities.

resultsIn the metformin-treated group, the DN incidence rates were 7.02%, 8.09%, 9.24%, and 10.75% for metformin administered at cDDDs of < 3 0, 30 to 120, 120 to 240, and > 240, respectively. After adjustments for relevant variables, relative to sulfonylurea-treated patients, patients who received metformin at cDDDs of < 30, 30 to 120, 120 to 240, and > 240 exhibited adjusted hazard ratios (95% CIs) for DN of 1.06 (1.03-1.09), 1.24 (1.21-1.27), 1.45 (1.41-1.49), and 1.72 (1.65-1.80), respectively.

conclusionsIn patients with T2DM, metformin treatment exhibited a dose-dependent relationship with an increased DN risk after 5 years of follow-up. Further large-scale prospective studies are warranted to confirm these findings and elucidate the biological mechanisms underlying this observed association.

Identifiers

PMID42730863

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