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Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder and is associated with various metabolic diseases, including type 2 diabetes mellitus. There are no approved drugs for NAFLD, and the only approved treatment option is weight reduction. As insulin resistance plays an important role in the development of NAFLD, many anti-diabetic drugs have been evaluated for the treatment of NAFLD. Improvement of liver enzymes has been demonstrated by many anti-diabetic drugs, but histological assessment still remains insufficient. Pioglitazone could become the first-line therapy for T2DM patients with NAFLD, based on evidence of histological improvement in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liraglutide, another promising alternative, is not yet recommended in patients with NAFLD/NASH due to limited evidence. Therefore, well-designed randomized controlled trials should be performed in the near future to demonstrate if and how anti-diabetic drugs can play a role in the treatment of NAFLD.

SUBMITTER: Kim KS

PROVIDER: S-EPMC7641556 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease.

Kim Kyung-Soo KS Lee Byung-Wan BW

Clinical and molecular hepatology 20200814 4

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder and is associated with various metabolic diseases, including type 2 diabetes mellitus. There are no approved drugs for NAFLD, and the only approved treatment option is weight reduction. As insulin resistance plays an important role in the development of NAFLD, many anti-diabetic drugs have been evaluated for the treatment of NAFLD. Improvement of liver enzymes has been demonstrated by many anti-diabetic drugs, but histolo ...[more]

PMID: 32791578

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Project description:BACKGROUND:Fatty liver is associated with obesity, type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. While there are no approved drugs for the treatment of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis, strategies to ameliorate fatty liver often target these related diseases. We sought to determine if any medications approved by the US Food and Drug Administration to treat diabetes are helpful in reducing weight and improving steatohepatitis in patients with NAFLD. METHODS:We conducted a systematic review of published and unpublished studies evaluating the comparative effectiveness and harms of diabetes medications for the treatment of NAFLD. We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials through 3rd quarter, 2019 using terms for included drugs and indications. RESULTS:We screened 1591 citations and included 18 trials of diabetes drugs to treat NAFLD. Studies of metformin found no difference from placebo in steatosis, fibrosis, NAFLD activity score, or resolution of NASH. While weight and glucose control were improved with metformin, it did not substantially impact liver disease. Studies of pioglitazone in NASH patients found benefits in liver function, liver fat, and NASH resolution, though significant increases in weight may be cause for concern. Evidence for other thiazolinediones was more limited and had somewhat mixed results, but findings were generally consistent with those for pioglitazone: liver fat and function and glucose measures improved, but weight also increased. We found some evidence that liraglutide improves liver fat, liver function, and HbA1c and is effective at resolving NASH and reducing weight. Exenatide performed less well but also resulted in significant reductions in liver fat and weight. CONCLUSIONS:Consistent with existing clinical practice guidelines, which recommend lifestyle intervention and treatment for comorbidities related to fatty liver disease as first-line treatment, trial evidence supports the efficacy of some diabetes drugs (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with some diabetes drugs may warrant caution. Larger trials are needed to better characterize the efficacy and harms of diabetes pharmacotherapy in these patients.

Project description:The prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be 26.3% among the US population. A subset of this population exhibits an aggressive histological phenotype, nonalcoholic steatohepatitis (NASH) with ≥ stage 2 fibrosis, which may progress to cirrhosis. The definition of NAFLD excludes excessive alcohol intake, which is well known to cause alcoholic liver disease and will not be discussed here. Most NAFLD clinical trials use ~14 drinks per week as the cutoff for excessive alcohol intake. Alcohol consumption below this threshold, which we define as moderate alcohol consumption, is common in the US. According to the 2012 Behavioral Risk Factor Surveillance System (BRFSS), 56% of the US adult population consume alcohol, but only 8.2% report drinking heavily and 18.3% report binge drinking. The American Association for the Study of Liver Diseases (AASLD) Practice Guidance of 2018 states that there are insufficient data to make a recommendation with regard to moderate alcohol consumption in patients with NAFLD, citing a lack of longitudinal studies that examine the impact of moderate alcohol consumption on disease progression and its extrahepatic harms versus benefits, specifically in individuals with established NAFLD. NAFLD prevalence studies have generally noted a negative correlation between modest alcohol consumption and NAFLD. However, prevalence studies have limited application to patients with established NAFLD who present to the clinic. There can also be many confounding factors, because modest alcohol consumption is also negatively associated with some NAFLD risk factors, and those risk factors may not be adequately adjusted for in analyses. The prevalence of NASH with significant fibrosis (≥ F2) is more important because this is the group that is believed to have progressive disease. Thus, cohort studies of disease progression are more important from the patient's standpoint. Because these patients have already developed NAFLD or NASH, their interest lies in their odds of disease progression if they have moderate alcohol consumption compared to abstinence. It is also noteworthy that cardiovascular disease is the most important cause of death among patients with NAFLD. Moderate alcohol consumption has been associated with a reduction in overall mortality, but mostly in cardiovascular mortality. However, this protective effect has not been demonstrated specifically in patients with NAFLD.

Project description:BackgroundNicotinamide has been reported to protect against liver steatosis and metabolic imbalances in nonalcoholic fatty liver disease (NAFLD) in animal models.ObjectivesThe objective was to investigate the efficacy and safety of nicotinamide supplementation in diabetic NAFLD patients.DesignThis is a prospective randomized controlled open label study.MethodsSeventy diabetic NAFLD patients were randomly assigned either to the nicotinamide group (n = 35) who received nicotinamide 1000 mg once daily for 12 weeks in addition to their antidiabetic therapy or the control group (n = 35) who received their antidiabetic therapy only. The primary outcome was improvement in steatosis score, while secondary outcomes included assessment of liver stiffness, liver enzymes, lipid profile, insulin resistance, serum malondialdehyde, serum adiponectin, and patients' quality of life (QOL).ResultsOnly 61 patients completed the study; 31 in the nicotinamide group and 30 in the control group. Comparisons between groups and within groups revealed nonsignificant changes in steatosis and fibrosis scores. However, significant reduction was observed in liver enzymes with a median decrease in alanine transaminase of 26.6% versus 0.74% in nicotinamide and control groups, respectively. After 12 weeks of treatment, the nicotinamide group showed significantly lower levels of low-density lipoprotein cholesterol (p value = 0.004), total cholesterol (p value = 0.006), and insulin resistance marker (p value = 0.005) compared with control. Serum triglycerides, malondialdehyde, and adiponectin levels were all comparable between the two groups. Regarding QOL, a significant improvement was detected in the total scores and the activity and fatigue domains scores.ConclusionNicotinamide at a dose of 1000 mg daily was tolerable, improved metabolic abnormalities and QOL of diabetic NAFLD patients with no effect on liver fibrosis or steatosis.Trial registrationThe study was registered at clinicaltrials.gov and given the ID number: 'NCT03850886'. https://clinicaltrials.gov/ct2/show/NCT03850886.

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Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease.

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Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease.

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