Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Its prevalence ranges 10–24% in the general population, reaching 60–95% and 28–55% in obese and diabetic patients, respectively. Although the etiology of NAFLD is still unclear, several lines of evidences have indicated a pathogenetic role of insulin resistance in this disorder. This concept has stimulated several clinical studies where antidiabetic drugs, such as insulin sensitizers including metformin, have been evaluated in insulin-resistant, NAFLD patients. These studies indicate that metformin might be of benefit in the treatment of NAFLD, also in nondiabetic patients, when associated to hypocaloric diet and weight control. However, the heterogeneity of these studies still prevents us from reaching firm conclusions about treatment guidelines. Moreover, metformin could have beneficial tissue-specific effects in NAFLD patients irrespective of its effects as insulin sensitizer.

Objective: We aimed at evaluating whether the addition of low-dose metformin to dietary treatment could be an effective approach in nondiabetic patients with nonalcoholic fatty liver disease (NAFLD). Methods: We carried out a 6-month prospective study in a series of overweight or obese patients with ultrasonographic diagnosis of hepatic steatosis. In total, 50 patients were enrolled and randomized into two groups: the first group (n ¼ 25) was given metformin (1 g per day) plus dietary treatment and the second group (n ¼ 25) was given dietary treatment alone. Results: At the end of the study, the proportion of patients with echographic evidence of fatty liver was reduced in both the metformin (Po0.0001) and the diet group (P ¼ 0.029). Moreover, patient body mass index and waist circumference significantly decreased in both groups (Po0.001). Fasting glucose, insulin resistance (evaluated as homeostasis model assessment of insulin resistance (HOMA-IR)) and serum adiponectin decreased in both groups, although these changes reached statistical significance only in the metformin group. In this group, HOMA-IR decreased from 3.3±1.6 to 2.4±1.2 (P ¼ 0.003), whereas it decreased from 3.2 ± 1.6 to 2.8 ± 1.1 (not significant, NS) in the diet group. Similarly, the proportion of patients with impaired fasting glucose declined from 35 to 5% (P ¼ 0.04) in the metformin and from 32 to 12% (NS) in the diet group. At baseline, B40% of patients in both groups met the diagnostic criteria of metabolic syndrome. This proportion decreased to 20% in the metformin group (P ¼ 0.008) and to 32% in the diet group (NS). Conclusions: In our 6-month prospective study, both low-dose metformin and dietary treatment alone ameliorated liver steatosis and metabolic derangements in patients with NAFLD. However, metformin was more effective than dietary treatment alone in normalizing several metabolic parameters in these patients.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Several lines of evidence have indicated a pathogenic role of insulin resistance, and a strong association with type 2 diabetes (T2MD) and metabolic syndrome. Importantly, NAFLD appears to enhance the risk for T2MD, as well as worsen glycemic control and cardiovascular disease in diabetic patients. In turn, T2MD may promote NAFLD progression. The opportunity to take into account NAFLD in T2MD prevention and care has stimulated several clinical studies in which antidiabetic drugs, such as metformin, thiazolidinediones, GLP-1 analogues and DPP-4 inhibitors have been evaluated in NAFLD patients. In this review, we provide an overview of preclinical and clinical evidences on the possible efficacy of antidiabetic drugs in NAFLD treatment. Overall, available data suggest that metformin has beneficial effects on body weight reduction and metabolic parameters, with uncertain effects on liver histology, while pioglitazone may improve liver histology. Few data, mostly preclinical, are available on DPP4 inhibitors and GLP-1 analogues. The heterogeneity of these studies and the small number of patients do not allow for firm conclusions about treatment guidelines, and further randomized, controlled studies are needed.

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The 5.6% prevalence of bilateral foci in sMTC suggests that total thyroidectomy should remain the standard of care for initial surgery, as less complete thyroid surgery may fail to address fully the primary site of disease. Whether ipsilateral tumor focality should be an independent factor determining the need for completion thyroidectomy when sMTC is diagnosed after hemithyroidectomy remains to be determined.

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