A look to the future in non‐alcoholic fatty liver disease: Are glucagon‐like peptide‐1 analogues or sodium‐glucose co‐transporter‐2 inhibitors the answer?

Abstract

The increasing prevalence of diabetes and non-alcoholic fatty liver disease (NAFLD) is a growing public health concern associated with significant morbidity, mortality and economic cost, particularly in those who progress to cirrhosis. Medical treatment is frequently limited, with no specific licensed treatments currently available for people with NAFLD. Its association with diabetes raises the possibility of shared mechanisms of disease progression and treatment. With the ever-growing interest in the non-glycaemic effects of diabetes medications, studies and clinical trials have investigated hepatic outcomes associated with the use of drug classes used for people with type 2 diabetes (T2D), such as glucagon-like peptide-1 (GLP-1) analogues or sodium-glucose co-transporter-2 (SGLT2) inhibitors. Studies exploring the use of GLP-1 analogues or SGLT2 inhibitors in people with NAFLD have observed improved measures of hepatic inflammation, liver enzymes and radiological features over short periods. However, these studies tend to have variable study populations and inconsistent reported outcomes, limiting comparison between drugs and drug classes. As these drugs appear to improve biomarkers of NAFLD, clinicians should consider their use in patients with NAFLD and T2D. However, further evidence with greater participant numbers and longer trial durations is required to support specific licensing for people with NAFLD. Larger trials would allow reporting of major adverse hepatic events, akin to cardiovascular and renal outcome trials, to be determined. This would provide a more meaningful evaluation of the impact of these drugs in NAFLD. Nevertheless, these drugs represent a future potential therapeutic avenue in this difficult-totreat population and may beget significant health and economic impacts.

Influence of cardiometabolic comorbidities on myocardial function, infarction, and cardioprotection: Role of cardiac redox signaling

“…Another novel antidiabetic drug class, SGLT2 inhibitors, are currently under consideration for the therapy of NAFLD/NASH [402]. Empagliflozin improved markers of liver fibrosis and steatosis in NAFLD patients with and without T2DM [403,404].…”

Glucagon-Like Peptide 1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors and Risk of Nonalcoholic Fatty Liver Disease Among Patients With Type 2 Diabetes

“…There has been a growing interest in the effects of second-line antidiabetes drugs, such as glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, on reducing hepatic fat content (7,8). In randomized controlled trials (RCTs), GLP-1 RAs have been associated with the resolution of established NASH compared with placebo (9,10).…”

Diabetes and NAFLD: a high-risk cohort with definite therapeutic potential

“…In conclusion, we are living a totally new era in the pharmacologic treatment of type 2 diabetes and patients with NAFLD are likely to take the greatest advantage from novel agents. The beneficial effects of GLP-1RAs and SGLT-2Is on metabolic outcomes extend well beyond the area of diabetes, namely to obesity, cardiovascular risk, heart failure and renal disease [93,94] , and might soon be available for NAFLD patients outside of T2DM [95,96] . Table 2.…”