Patients with nonalcoholic fatty liver disease and concomitant type 2 diabetes mellitus are at an increased risk of disease progression, leading to cirrhosis and hepatocellular carcinoma. Lifestyle interventions leading to weight loss, including a Mediterranean diet and increased physical activity, are key to improving outcomes in this group of patients. A pharmacological therapeutic approach that could reduce liver steatosis, inflammation, and consequent fibrosis is still not defined. Pioglitazone, an insulin sensitizer, can be considered in these patients for achieving adequate glycemic control, as current evidence suggests a benefit in terms of histological improvement. Many candidate pharmacological agents, including other insulin sensitizers, lipid-lowering drugs, and antioxidants, are currently being tested to treat NAFLD. Targeting anti-inflammatory, anti-fibrotic, and anti-apoptotic pathways as well as bile acid metabolism and gut microbiota is also under investigation. Better quality evidence for treating NAFLD, especially in type 2 diabetes patients, is needed and should be available in the foreseeable future.
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