The Skinny on Reducing Liver Fat with Empagliflozin in Type 2 Diabetes

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Summary 

• Empagliflozin leads to substantial reductions in liver fat in patients with type 2 diabetes mellitus (T2DM).
• Empagliflozin also leads to a significant decrease in the liver function test alanine aminotransferase (ALT).
• Levels of aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) were also reduced, although not significantly with empagliflozin treatment in patients T2DM.

Non-alcoholic fatty liver disease (NAFLD) is a build up of fat on the liver, but not related to drinking alcohol.

Mabrish Mithal, MD, of Medanta-The Medicity Hospital in Delhi, India states, “NAFLD can progress to [non-alcoholic steatohepatitis, NASH], and subsequently to cirrhosis and even cancer of the liver, potentially fatal conditions. NAFLD is particularly common in diabetes. Medications to treat NAFLD/NASH are sorely needed.”

Empagliflozin is a sodium glucose cotransporter-2 (SGLT-2) inhibitor that has been shown in rodent models to reduce liver fat. Empagliflozin and other SGLT-2 inhibitors are used to lower blood sugar in adults with T2DM.

Dr. Mithal and colleagues from Medanta-The Medicity Hospital hoped to determine if empagliflozin could reduce liver fat in T2DM patients with NAFLD; they presented their E-LIFT trial as a late breaking abstract at the ENDO 2018 annual meeting in Chicago, Illinois.

The Study

The E-LIFT trial is a single-center, prospective, open-label, randomized controlled trial looking at 50 patients with T2DM and NAFLD. Subjects were randomized to receive standard treatment for T2DM plus empagliflozin or standard treatment without empagliflozin. The primary outcome was liver fat change over 20 weeks.

The Results

• Empagliflozin combined with standard treatment reduced the amount of liver fat more than standard treatment alone (4%; p<.0001).
• At the end of 20 weeks MRI-derived proton density fat fraction was 11.3% vs 16.2% at baseline in the empagliflozin group (P<.0001) and 15.5% vs 16.4%, respectively, in the standard-treatment group (P=.057).
• ALT, AST, and GGT were lowered in the empagliflozin group (–10.9 IU/L, P=0.005, –7.7 IU/L; P=.212 and –11 IU/L; P=.057 respectively). 
• There were no significant differences between fasting plasma glucose and HbA1C between the empagliflozin and control groups at 20 weeks (p=0.850; HbA1C, p=0.880 respectively).

Implication for Physicians 

• Adding empagliflozin to standard treatment for T2DM significantly reduced liver fat at 20 weeks compared to standard treatment alone.
• No significant differences between groups were found with regards to HbA1c or fasting glucose levels.
• “While our findings do not prove that empagliflozin will help treat NAFLD or prevent NASH, the initial results are promising and open up the possibility that empagliflozin may provide additional benefits for patients with diabetes,” Dr. Mithal stated. 

References:

Kuchay MS, Krishan S, Mishra SK, Mithal A. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT trial). Paper presented at The Endocrine Society Annual Meeting (ENDO 2018); March 2018; Chicago, IL.