Pharmacotherapy of type 2 diabetes in patients with chronic liver disease: focus on nonalcoholic fatty liver disease

ABSTRACT

Introduction: Pharmacotherapy used to treat type 2 diabetes mellitus (T2DM) is facing a paradigm shift in clinical practice with recent cardiovascular (CV) outcome trials having a substantial impact on drug prescription with treatment having a more tailored approach. In patients with T2DM, the issue of chronic liver disease is multifaceted. However, a clinical evidence is emerging on the beneficial effect of antidiabetic medications on nonalcoholic fatty liver disease (NAFLD).

Areas covered: The authors provide a synopsis on the current and upcoming pharmacotherapy for NAFLD, including the challenges with their development, focusing on drugs for T2DM. Clinical data on the potential benefits and safety issues are assessed with the aim of proposing an individualized algorithm for patient management. Both MEDLINE and ClinicalTrials.Gov are used to derive the relevant information.

Expert opinion: Considering the pivotal role of insulin resistance in NAFLD, insulin sensitizers should be the treatment of choice. Accordingly, pioglitazone is the only drug with a significant effect on liver fibrosis, the driver of disease progression and long-term outcome. Among new glucose-lowering drugs, glucagon-like-peptide 1 receptor agonists or sodium-glucose cotransporter type 2 inhibitors have shown positive effects in phase II studies and are qualifying as potential candidates for NAFLD treatment in diabetes.

KEYWORDS:

• Nonalcoholic fatty liver disease
• type 2 diabetes
• chronic liver disease
• drug-induce liver injury
• treatment

Article highlights

• Nonalcoholic fatty liver disease (NAFLD) is a so-far neglected co-morbidity of type 2 diabetes mellitus (T2DM) without any approved pharmacotherapy.

• Patients with T2DM and definite NAFLD warrant a multidisciplinary approach focused on weight control (weight loss >10% body weight, ideally via non-pharmacological interventions), which is associated with improvement in fibrosis, the main driver of disease outcome.

• The new classes of glucose-lowering drugs are being exploited for NAFLD treatment, in the hope they might prevent or mitigate progressive liver disease, especially necro-inflammation and fibrosis.

• The current body of evidence (published and unpublished) shows promising results for the old class of thiazolidinediones, as well as for recent glucagon-like-peptide 1 receptor agonists and sodium-glucose cotransporter type 2 inhibitors.

• Tailored pharmacotherapy for NAFLD-associated T2DM is a present clinical challenge and both efficacy (on metabolic and liver-related parameters), as well as non-glucose-related benefits (reduced body weight and cardiovascular risk) and safety issues (urogenital tract infections and gastrointestinal discomfort) of new antidiabetic agents should drive the selection of optimal combinations.

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Declaration of interest

G Marchesini has served on the advisory boards of Gilead Sciences, Eli Lilly and Company, and AstraZeneca, and has taken part in clinical studies on NAFLD and T2DM sponsored by Sanofi, Eli Lilly, NovoNordisk, Janssen Pharmaceuticals, GlaxoSmithKline, Genfit SA, and Gilead Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded. Authors are supported by their employers, the University of Bologna.