Selection and Warning of Evidence-Based Antidiabetic Medications for Patients With Chronic Liver Disease

Abstract

The global prevalence of chronic liver disease and diabetes mellitus (DM) has gradually increased potentially due to changes in diet and lifestyle. The choice of antidiabetic medications for patients with coexisting DM and chronic liver disease is complicated. Severe liver injury may decrease the metabolism of antidiabetic medications, resulting in elevated drug concentrations and adverse effects. The choice of antidiabetic medications in patients with chronic liver disease has not been well studied. The long-term outcomes of antidiabetic medications in patients with chronic liver disease have gained attention recently. Herein, we reviewed relevant articles to extend our understanding on the selection and warning of antidiabetic medications for patients with chronic liver disease.

Autoimmune liver diseases and diabetes

“…Possible explanations suggested by the authors include corticosteroid treatment in patients with AIH resulting in postprandial hyperglycaemia; pro-inflammatory cytokines likely to be released in AIH causing insulin resistance in adipose tissue, skeletal muscle, and liver by inhibiting insulin signal transduction; and finally, diabetes and hyperglycaemia being a complication of chronic liver diseases. Another possible explanation for the more frequent insulin treatment in the patients with T2D and AIH could be the presence of liver cirrhosis in a proportion of the AIH patients, as insulin is a strongly recommended treatment of T2D in patients with liver cirrhosis [45][46][47][48][49].…”

“…Treatment regimens include several different classes of oral and injectable antidiabetic medications and take into account potential comorbidity [101][102][103]. A detailed summary of diabetes treatment in chronic liver disease patients is beyond the scope of this review and has previously been discussed thoroughly [47][48][49]104]; however, we want to address some overall considerations on the topic.…”

“…Generally, both oral and injectable glucose-lowering medication is considered safe in patients with noncirrhotic chronic liver disease, including patients with autoimmune liver disease [47][48][49]104]. Indeed, improvement in NAFLD has been demonstrated with the example of dipeptidyl peptidase-4 inhibitors [105][106][107] and GLP-1 receptor agonists [108,109]; drugs that could be used in combination with the specific treatments for autoimmune liver disease.…”

“…For instance, patients with liver cirrhosis have reduced liver parenchymal function for the metabolization of drugs [110], potential portosystemic and intrahepatic shunting resulting in decreased first-pass clearance in the liver [87], reduced albumin concentration and albumin function potentially reducing the ability to bind drugs [111], and chronic kidney disease potentially reducing drug elimination [87,112]. Therefore, caution to oral glucose-lowering drugs is generally recommended in patients with liver cirrhosis, and in the case of decompensation, insulin is considered the main treatment [45][46][47][48][49]. In any case, close monitoring of blood glucose is necessary as insulin sensitivity and metabolization within the liver may vary with varying degrees of reduced liver function increasing the risk of hypo-and hyper-glycaemia during insulin treatment [47][48][49].…”

Investigation of the pathogenesis of liver cirrhosis associated with type 2 diabetes mellitus via bioinformatic analysis

“…Therefore, insulin resistance is more severe in patients with liver cirrhosis associated with T2DM. Considerably high insulin resistance is the main factor affecting the development and prognosis of liver cirrhosis associated with T2DM [24]. However, there are no clinical treatments that may be considered the best therapy for patients with liver cirrhosis associated with T2DM.…”