Empagliflozin Eyed for Fatty Liver Disease in Type 2 Diabetes

Christine Wiebe

March 22, 2018

CHICAGO, Illinois — The type 2 diabetes drug empagliflozin (Jardiance, Lilly/Boehringer Ingelheim) has shown promise in the treatment of nonalcoholic fatty liver disease (NAFLD) in the small E-LIFT study, presented here March 19 at ENDO 2018: The Endocrine Society Annual Meeting.

Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reduced liver fat from 16.2% to 11.3% compared with a control in a trial of just under 50 patients who also had type 2 diabetes, reported Mohammad Shafi Kuchay, MD, Medanta, Gurgaon, India.

"This is the first study that shows this SGLT2 inhibitor reduces liver fat," he said. "We don't know if it reduces inflammation, or if it reduces cardiovascular risk later on." Larger studies are needed to determine that, he said. However, he added that reducing liver fat is believed to be the first step in improving liver disease.

Half of Patients With Type 2 Diabetes Have Fatty Livers

Shafi Kuchay explained that the prevalence of fatty liver in patients with type 2 diabetes is estimated to be 50% and higher, leading to numerous trials looking for new drugs to treat NAFLD.

Finding a glucose-lowering drug that also treats NAFLD would be particularly appealing, as would weight loss (which accompanies some glucose-lowering agents), because obesity is often also associated with NAFLD.

According to a review of the topic (Aliment Pharmacol Ther. 2017;46:494-507), studies in patients with type 2 diabetes have demonstrated improvement in the liver enzyme alanine aminotransferase (ALT) and weight loss with the SGLT2 inhibitors ipragliflozin (Suglat, Astellas) and canagliflozin (Invokana, Janssen), as well as a reduction in fatty liver index score.

And in a recent trial (J Clin Endocrinol Metab. 2017;102:407-415) with another class of type 2 diabetes drug, the injectable glucagonlike peptide-1 (GLP-1) receptor agonist liraglutide (Victoza, Novo Nordisk), a dose of 1.2 mg daily was associated with significant decreases in body weight and HbA1c, and a marked relative reduction in liver fat content of 31% (P < .0001) in a similar patient population.

The current study included 22 patients treated with empagliflozin 10 mg daily for 20 weeks who were compared with 20 patients who received standard treatment for type 2 diabetes without empagliflozin. Liver fat was measured using an MRI-derived proton density fat fraction technique. Liver function was measured using serum aspartate aminotransferase (AST), ALT, and gamma-glutamyl transpeptidase (GGT) levels.

Only improvements in ALT were significantly better in those taking empagliflozin compared with the control group.

Overall, 25% of the control group had an increase in liver fat during the study, half had no change, and 25% had a reduction.

In the empagliflozin group, no patients had increased liver fat, 23% remained stable, and 77% experienced a decrease in liver fat.

Both groups saw some improvement in HbA1c levels, but the difference between groups was not significant, Shafi Kuchay reported.

Some participants in the treatment group had no weight loss but still showed a decrease in liver fat, he observed. In response to delegates' questions about this, he said different mechanisms of action may be at play in the way an SGLT-2 inhibitor reduces liver fat and lowers blood glucose.

Shafi Kuchay noted that other trials are ongoing with glucose-lowering agents in patients with type 2 diabetes and NAFLD.

A trial in Malaysia, for instance, is recruiting patients with NAFLD to receive empagliflozin 25 mg daily for 6 months. Patients will then undergo another liver biopsy to determine treatment effect.

Other diabetes agents being studied in NAFLD include another SGLT2 inhibitor, tofogliflozin (Chugai Pharmaceuticals), and the GLP-1 agonist exenatide (Bydureon, AstraZeneca).

Shafi Kuchay has reported no relevant financial relationships.

ENDO 2018. March 19, 2018; Chicago, Illinois. Abstract OR27-2

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