The Role of Metformin in the Management of NAFLD

Mazza, Angela; Fruci, Barbara; Garinis, Giorgia Anna; Giuliano, Stefania; Malaguarnera, Roberta; Belfiore, Antonino

doi:10.1155/2012/716404

Cited by 155 publications

(133 citation statements)

References 111 publications

(151 reference statements)

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“…While the prevalence of NAFLD ranges 10-24% in the general population, it may reach 60-95% and 28-55% in severely obese and diabetic patients, respectively [8] . In this context, it has be hypothesized that NAFLD may be considered as a new target for T2DM prevention and treatment [9] .…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Scheen

2014

Clin Pharmacokinet

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SUMMARYPatients with type 2 diabetes have an increased risk of chronic liver disease such as nonalcoholic fatty liver disease and steatohepatitis, and about one third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents, such as metformin and sulphonylureas, may be a concern in case of hepatic impairment (HI). New glucose-lowering agents targeting the incretin system are increasingly used for the management of type 2 diabetes. Incretin-based therapies comprise oral inhibitors of dipeptidyl peptidase-4 (DPP-4) (gliptins) or injectable glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review summarizes the available data regarding the use of both incretin-based therapies in patients with HI. In contrast to old glucose-lowering agents, they were evaluated in specifically designed acute pharmacokinetic studies in patients with various degrees of HI and -Obese patients with type 2 diabetes often have non-alcoholic fatty liver disease or steatohepatitis and the use of incretin-based therapies appears mostly favourable in these patients regarding both efficacy and safety.-There is no reported clinical experience with the use of either DPP-4 inhibitors or GLP-1 receptor agonists in diabetic patients with moderate to severe hepatic impairment, so that caution is required in patients with advanced cirrhosis.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Scheen

2014

Clin Pharmacokinet

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“…The authors explained the strict inclusion criteria with the histological definition of NAFLD or NASH, while only three RCTs were included as barriers to the meta-analysis with regards to the effect of metformin on NAFLD. However, several studies, including more recent RCT data, and an additional review have shown that metformin may improve metabolic variables in NAFLD patients, especially in patients meeting the diagnostic criteria of metabolic syndrome (18). Therefore, the aim of this systematic review and meta-analysis was to further assess the beneficial and harmful effects of metformin on NAFLD.…”

Section: Metformin In Non-alcoholic Fatty Liver Diseasementioning

confidence: 99%

Metformin in non-alcoholic fatty liver disease: A systematic review and meta-analysis

et al. 2012

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Abstract. Non-alcoholic fatty liver disease (NAFLD) related to insulin resistance (IR) is a growing global health concern. Recent studies have indicated that metformin could improve IR and may be beneficial in the treatment of NAFLD. This study aimed to assess the beneficial or harmful effects of metformin in NAFLD. We searched Medline and four other databases during April 2012. Selection criteria were randomized clinical trials comparing metformin with placebo or other interventions for treating NAFLD patients. The primary outcome was histological response. The secondary outcomes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), homeostasis model assessment of IR (HOMA-IR), body mass index (BMI) and adverse events. Dichotomous data were reported as odds ratio (OR), while continuous data were calculated as the mean difference (MD), both with 95% confidence intervals (CI). Random and fixed effects meta-analyses were performed. Nine studies were included, involving 417 participants, and conducted for a time period ranging from 4 to 12 months. In the treated participants, improvements were observed in ALT (MD, -8.12 U/l; P=0.03), AST (MD, -4.52 U/l; P=0.04), HOMA-IR (MD, -0.61; P=0.005) and BMI (MD, -0.82 kg/m 2 ; P=0.04), but not in histological response: steatosis (P=0.66), inflammation (P=0.91), hepatocellular ballooning (P= 0.25) and fibrosis (P= 0.90). Sub-analysis of non-alcoholic fatty steatohepatitis showed that metformin failed to improve any pooled outcome. Adverse events were poorly reported. Current information indicates that metformin improves liver function, HOMA-IR and BMI to some extent, but not histological response in NAFLD patients. This finding could serve as a stimulus for future studies investigating issues such as dose-responsiveness, safety and patient tolerance to metformin therapy.

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“…Especially no increased risk of lactic acidosis has been reported. Metformin may potentially exert beneficial effects in patients with NAFLD, although the evidence remains rather scarce [59][60][61].…”

Section: Metformin In Patients With Hepatic Dysfunctionmentioning

confidence: 99%

Metformin revisited: A critical review of the benefit–risk balance in at-risk patients with type 2 diabetes

Scheen

Paquot

2013

Diabetes & Metabolism

150

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Metformin is unanimously considered as the first-line glucose-lowering agent. Theoretically, however, it cannot be prescribed in a large proportion of patients with type 2 diabetes because of the presence of numerous contraindications corresponding to situations that may increase the risk of lactic acidosis. Various observational data from real life showed that many diabetic patients considered as "at risk" still receive metformin, often without appropriate dose adjustment, apparently without any harm, especially no increased risk of lactic acidosis. More interestingly, recent data suggest that type 2 diabetes patients who are considered as being "at risk" because of the presence of traditional contraindications still take benefit from metformin therapy, with a reduction of morbidity and mortality compared with other glucose-lowering agents, more particularly sulfonylureas. The present review analyzes the benefit-risk balance of metformin therapy in special populations, namely patients with stable coronary artery disease, acute coronary syndrome or myocardial infarction, congestive heart failure, renal impairment or chronic kidney disease, hepatic dysfunction and chronic respiratory insufficiency, all conditions that may theoretically increase the risk of lactic acidosis. A special attention will be devoted to elderly patients with type 2 diabetes. Indeed, this population is growing rapidly and older patients may cumulate several comorbidities

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The Role of Metformin in the Management of NAFLD

Cited by 155 publications

References 111 publications

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Metformin in non-alcoholic fatty liver disease: A systematic review and meta-analysis

Metformin revisited: A critical review of the benefit–risk balance in at-risk patients with type 2 diabetes

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