Impact of Dipeptidyl Peptidase-4 Inhibitors on Aminotransferases Levels in Patients with Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trial

Background: Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are highly prevalent diseases that constitute enormous public health problems. The efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors in blood glucose control in T2DM patients with NAFLD has been established,...

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Main Authors: Gang Ma, MD, Song Zhang, MD, Baozhong Yu, MD
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Current Therapeutic Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0011393X24000389
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author Gang Ma, MD
Song Zhang, MD
Baozhong Yu, MD
author_facet Gang Ma, MD
Song Zhang, MD
Baozhong Yu, MD
author_sort Gang Ma, MD
collection DOAJ
description Background: Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are highly prevalent diseases that constitute enormous public health problems. The efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors in blood glucose control in T2DM patients with NAFLD has been established, but little is known about its effect on liver enzyme levels. Objective: This meta-analysis aimed to evaluate the influences of DPP-4 inhibitors on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with T2DM and NAFLD. Methods: To identify the relevant studies, we searched PubMed, Embase, the Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. Means differences in liver enzymes and metabolic outcomes were meta-analyzed using a random-effects model, with subgroup analyses by gender, age, area, follow-up duration, and type of DPP-4 inhibitor. Quality assessment of the included studies was conducted using the revised Cochrane risk of bias tool. Results: A total of 1323 patients from 16 studies were included in this meta-analysis. The results of analysis of DPP-4 inhibitors showed that the mean difference was –6.19 (95% confidence interval [CI]: –9.45 to –2.92) for ALT and –5.17 (95% CI: –8.10 to –2.23) for AST; this effect was statistically significant from the placebo group which indicates the beneficial effect on liver enzymes. Subgroup analysis revealed that while there were no significant gender differences in enzyme reductions, individuals over 55 years old experienced more pronounced decreases in ALT. Notably, Asian studies showed significant reductions in liver enzymes, contrasting with the minor variations observed in Euramerican regions, and the effectiveness of DPP-4 inhibitors was particularly pronounced during shorter follow-up periods, with effects diminishing over time. Regarding secondary outcomes, there was a notable improvement in gamma-glutamyl transpeptidase, with a mean reduction, and in HbA1c levels, indicating improved glycemic control. Homeostatic model assessment for insulin resistance levels also improved, reflecting better insulin sensitivity. Additionally, adverse event analysis confirmed that DPP-4 inhibitors were well-tolerated with a favorable safety profile. Conclusions: DPP-4 inhibitors appear to enhance glycemic control and improve liver enzyme levels, suggesting a potentially effective therapeutic approach for managing T2DM/NAFLD and highlighting their broader metabolic benefits.
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spelling doaj-art-9ba274c07f084e6a9fe8f59e7fbf936f2025-08-20T03:10:47ZengElsevierCurrent Therapeutic Research0011-393X2025-01-0110210076810.1016/j.curtheres.2024.100768Impact of Dipeptidyl Peptidase-4 Inhibitors on Aminotransferases Levels in Patients with Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled TrialGang Ma, MD0Song Zhang, MD1Baozhong Yu, MD2Department of hepatobiliary surgery, The First People's Hospital of Guangyuan, Guangyuan, Sichuan, China; Address correspondence to: Gang Ma, 490 Juguo Road, Lizhou District, Guangyuan, 628013 Sichuan, China.Departmant of Pharmacy, The First People's Hospital of Guangyuan, Guangyuan, Sichuan, ChinaClinical trial institutions, The First People's Hospital of Guangyuan, Guangyuan, Sichuan, ChinaBackground: Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are highly prevalent diseases that constitute enormous public health problems. The efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors in blood glucose control in T2DM patients with NAFLD has been established, but little is known about its effect on liver enzyme levels. Objective: This meta-analysis aimed to evaluate the influences of DPP-4 inhibitors on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with T2DM and NAFLD. Methods: To identify the relevant studies, we searched PubMed, Embase, the Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. Means differences in liver enzymes and metabolic outcomes were meta-analyzed using a random-effects model, with subgroup analyses by gender, age, area, follow-up duration, and type of DPP-4 inhibitor. Quality assessment of the included studies was conducted using the revised Cochrane risk of bias tool. Results: A total of 1323 patients from 16 studies were included in this meta-analysis. The results of analysis of DPP-4 inhibitors showed that the mean difference was –6.19 (95% confidence interval [CI]: –9.45 to –2.92) for ALT and –5.17 (95% CI: –8.10 to –2.23) for AST; this effect was statistically significant from the placebo group which indicates the beneficial effect on liver enzymes. Subgroup analysis revealed that while there were no significant gender differences in enzyme reductions, individuals over 55 years old experienced more pronounced decreases in ALT. Notably, Asian studies showed significant reductions in liver enzymes, contrasting with the minor variations observed in Euramerican regions, and the effectiveness of DPP-4 inhibitors was particularly pronounced during shorter follow-up periods, with effects diminishing over time. Regarding secondary outcomes, there was a notable improvement in gamma-glutamyl transpeptidase, with a mean reduction, and in HbA1c levels, indicating improved glycemic control. Homeostatic model assessment for insulin resistance levels also improved, reflecting better insulin sensitivity. Additionally, adverse event analysis confirmed that DPP-4 inhibitors were well-tolerated with a favorable safety profile. Conclusions: DPP-4 inhibitors appear to enhance glycemic control and improve liver enzyme levels, suggesting a potentially effective therapeutic approach for managing T2DM/NAFLD and highlighting their broader metabolic benefits.http://www.sciencedirect.com/science/article/pii/S0011393X24000389AminotransferasesDipeptidyl peptidase-4 inhibitorsMeta-analysisNonalcoholic fatty liver diseaseType 2 diabetes mellitus
spellingShingle Gang Ma, MD
Song Zhang, MD
Baozhong Yu, MD
Impact of Dipeptidyl Peptidase-4 Inhibitors on Aminotransferases Levels in Patients with Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trial
Current Therapeutic Research
Aminotransferases
Dipeptidyl peptidase-4 inhibitors
Meta-analysis
Nonalcoholic fatty liver disease
Type 2 diabetes mellitus
title Impact of Dipeptidyl Peptidase-4 Inhibitors on Aminotransferases Levels in Patients with Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trial
title_full Impact of Dipeptidyl Peptidase-4 Inhibitors on Aminotransferases Levels in Patients with Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trial
title_fullStr Impact of Dipeptidyl Peptidase-4 Inhibitors on Aminotransferases Levels in Patients with Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trial
title_full_unstemmed Impact of Dipeptidyl Peptidase-4 Inhibitors on Aminotransferases Levels in Patients with Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trial
title_short Impact of Dipeptidyl Peptidase-4 Inhibitors on Aminotransferases Levels in Patients with Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trial
title_sort impact of dipeptidyl peptidase 4 inhibitors on aminotransferases levels in patients with type 2 diabetes mellitus with nonalcoholic fatty liver disease a meta analysis of randomized controlled trial
topic Aminotransferases
Dipeptidyl peptidase-4 inhibitors
Meta-analysis
Nonalcoholic fatty liver disease
Type 2 diabetes mellitus
url http://www.sciencedirect.com/science/article/pii/S0011393X24000389
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