{"title":"Differential Effects of SGLT-2 Inhibitors on Liver Function and Nocturia in Patients with Type 2 Diabetes: A Randomized Controlled Trial.","authors":"Tetsuya Kawahara, Mikio Toda, Maiko Kanagawa, Nagahiro Toyama, Gen Suzuki, Chie Kawahara, Tetsuya Inazu","doi":"10.2147/DMSO.S547088","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This study investigated whether sodium-glucose cotransporter-2 inhibitors (SGLT-2is) improve liver function as a class effect and evaluated their effect on nocturia in patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD).</p><p><strong>Methods: </strong>A total of 135 patients with type 2 diabetes and MASLD were randomly assigned to receive tofogliflozin (20 mg/day), dapagliflozin (5 mg/day), or empagliflozin (10 mg/day). Primary outcomes included changes in liver function and fibrosis markers-various transferases, fibrosis-4 index, mac-2 binding protein glycan isomer, and shear wave speed-along with nocturia frequency. Secondary outcomes were glycemic control, body weight, and lipid profiles. Patients were followed for seven months.</p><p><strong>Results: </strong>The participants had a mean age of 61 years; 43% were female, HbA1c level was 8.7%, and the frequency of nocturia was 0.6 times. All three SGLT-2is significantly improved liver function markers, with no differences between groups. However, nocturia frequency significantly increased with empagliflozin (1.7 times) and dapagliflozin (1.9 times; both <i>p</i> < 0.001) but not with tofogliflozin (0.8 times; <i>p</i> = 0.503). Tofogliflozin resulted in a significantly smaller nocturia increase than the other two drugs (<i>p</i> < 0.001). However, this significant difference persisted up to 1 month; from 3 months onward, urinary frequency improved in all groups, and the difference was not observed. Glycemic control, body weight, and lipid profiles improved similarly across all groups.</p><p><strong>Conclusion: </strong>SGLT-2is improve liver function as a class effect, but their impact on nocturia frequency differs. Tofogliflozin, likely due to its shorter half-life, has the most favorable nocturia profile and may be preferable for patients at risk. The UMIN Clinical Trial Registry number for this study is UMIN000054278; Clinical Trials Registry date 28/04/2024.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"2611-2622"},"PeriodicalIF":3.0000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12319161/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DMSO.S547088","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: This study investigated whether sodium-glucose cotransporter-2 inhibitors (SGLT-2is) improve liver function as a class effect and evaluated their effect on nocturia in patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD).
Methods: A total of 135 patients with type 2 diabetes and MASLD were randomly assigned to receive tofogliflozin (20 mg/day), dapagliflozin (5 mg/day), or empagliflozin (10 mg/day). Primary outcomes included changes in liver function and fibrosis markers-various transferases, fibrosis-4 index, mac-2 binding protein glycan isomer, and shear wave speed-along with nocturia frequency. Secondary outcomes were glycemic control, body weight, and lipid profiles. Patients were followed for seven months.
Results: The participants had a mean age of 61 years; 43% were female, HbA1c level was 8.7%, and the frequency of nocturia was 0.6 times. All three SGLT-2is significantly improved liver function markers, with no differences between groups. However, nocturia frequency significantly increased with empagliflozin (1.7 times) and dapagliflozin (1.9 times; both p < 0.001) but not with tofogliflozin (0.8 times; p = 0.503). Tofogliflozin resulted in a significantly smaller nocturia increase than the other two drugs (p < 0.001). However, this significant difference persisted up to 1 month; from 3 months onward, urinary frequency improved in all groups, and the difference was not observed. Glycemic control, body weight, and lipid profiles improved similarly across all groups.
Conclusion: SGLT-2is improve liver function as a class effect, but their impact on nocturia frequency differs. Tofogliflozin, likely due to its shorter half-life, has the most favorable nocturia profile and may be preferable for patients at risk. The UMIN Clinical Trial Registry number for this study is UMIN000054278; Clinical Trials Registry date 28/04/2024.
期刊介绍：
An international, peer-reviewed, open access, online journal. The journal is committed to the rapid publication of the latest laboratory and clinical findings in the fields of diabetes, metabolic syndrome and obesity research. Original research, review, case reports, hypothesis formation, expert opinion and commentaries are all considered for publication.
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