New anti-diabetic agents for the treatment of non-alcoholic fatty liver disease: a systematic review and network meta-analysis of randomized controlled trials

Kongmalai, Tanawan; Srinonprasert, Varalak; Anothaisintawee, Thunyarat; Kongmalai, Pinkawas; McKay, Gareth; Attia, John; Thakkinstian, Ammarin

doi:10.3389/fendo.2023.1182037

Cited by 20 publications

(7 citation statements)

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“…Studies indicate that sitagliptin can significantly improve liver function and reduce liver fat, as evidenced by advanced imaging methods such as magnetic resonance spectroscopy. 87 The drug works by reducing cell death in liver cells, decreasing fat production in the liver, and managing oxidative stress and related inflammation. 88 In one clinical trial, researchers explored the effectiveness of combining sitagliptin with insulin glargine for treating NAFLD in T2DM patients, comparing it to the combination of liraglutide and metformin.…”

Section: Resultsmentioning

confidence: 99%

Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis

Hegazi,

Alalalmeh,

Shahwan

et al. 2024

DMSO

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Background Non-alcoholic fatty liver disease (NAFLD) is a common disease and has been increasing in recent years. To date, no FDA-approved drug specifically targets NAFLD. Methods The terms “Non-alcoholic Fatty Liver Disease” and “NAFLD” were used in a search of ClinicalTrials.gov on August 24, 2023. Two evaluators independently examined the trials using predetermined eligibility criteria. Studies had to be interventional, NAFLD focused, in Phase IV, and completed to be eligible for this review. Results The ClinicalTrials.gov database was searched for trials examining pharmacotherapeutics in NAFLD. The search revealed 1364 trials, with 31 meeting the inclusion criteria. Out of these, 19 were finalized for evaluation. The dominant intervention model was Parallel. The most prevalent studies were in Korea (26.3%) and China (21.1%). The most common intervention was metformin (12.1%), with others like Exenatide and Pioglitazone accounting for 9.1%. Conclusion Therapeutics used to manage NAFLD are limited. However, various medications offer potential benefits. Further investigations are definitely warranted.

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Section: Resultsmentioning

confidence: 99%

Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis

Hegazi,

Alalalmeh,

Shahwan

et al. 2024

DMSO

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“…Contrasting with SGLT2 inhibitors and thiazolidinediones, the association between NAFLD regression and DPP-4 inhibitors remains unclear . DPP-4 inhibitors are not significantly associated with weight change .…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease

Jang,

Kim,

Lee

et al. 2024

JAMA Intern Med

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ImportanceSeveral oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking.ObjectiveTo investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D).Design, Setting, and ParticipantsThis retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD.ExposuresReceiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days.Main Outcomes and MeasuresThe main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks.ResultsIn total, 80 178 patients (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) were followed up for 219 941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas.Conclusions and RelevanceThe results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.

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“…Hence, the management of MASLD/MASH focuses on improving body metabolic functions and reducing body weight. Antidiabetic and antiobesity drugs do improve and delay the effects of MASLD [ 96 ]. Studies are now also exploring the possibility of plant-based MNPs to reverse obesity and MASLD.…”

Section: Phytonanotherapy For Masld/mashmentioning

confidence: 99%

Phytonanotherapy for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease

Nendouvhada,

Sibuyi,

Fadaka

et al. 2024

IJMS

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Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease, is a steatotic liver disease associated with metabolic syndrome (MetS), especially obesity, hypertension, diabetes, hyperlipidemia, and hypertriglyceridemia. MASLD in 43–44% of patients can progress to metabolic dysfunction-associated steatohepatitis (MASH), and 7–30% of these cases will progress to liver scarring (cirrhosis). To date, the mechanism of MASLD and its progression is not completely understood and there were no therapeutic strategies specifically tailored for MASLD/MASH until March 2024. The conventional antiobesity and antidiabetic pharmacological approaches used to reduce the progression of MASLD demonstrated favorable peripheral outcomes but insignificant effects on liver histology. Alternatively, phyto-synthesized metal-based nanoparticles (MNPs) are now being explored in the treatment of various liver diseases due to their unique bioactivities and reduced bystander effects. Although phytonanotherapy has not been explored in the clinical treatment of MASLD/MASH, MNPs such as gold NPs (AuNPs) and silver NPs (AgNPs) have been reported to improve metabolic processes by reducing blood glucose levels, body fat, and inflammation. Therefore, these actions suggest that MNPs can potentially be used in the treatment of MASLD/MASH and related metabolic diseases. Further studies are warranted to investigate the feasibility and efficacy of phytonanomedicine before clinical application.

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New anti-diabetic agents for the treatment of non-alcoholic fatty liver disease: a systematic review and network meta-analysis of randomized controlled trials

Cited by 20 publications

References 78 publications

Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis

Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis

Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease

Phytonanotherapy for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease

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