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One More Benefit for SGLT-2 Inhibitors

May 5, 2018
 

Treatment method reduced the amount of liver fat more than standard treatment alone.

Non-alcoholic fatty liver disease (NAFLD) is a buildup of fat on the liver — though not related to drinking alcohol  — and is particularly common in diabetes. The results of the Effect of Empagliflozin on Liver Fat Content in Patients with Type 2 Diabetes Trial  (E-LIFT) showed that an oral SGLT2-inhibitor may provide substantial benefit to patients with type 2 diabetes and nonalcoholic fatty liver disease by aiding in the reduction of liver fat, according to findings from the trial.

NAFLD can progress to [nonalcoholic steatohepatitis], and subsequently to cirrhosis and even cancer of the liver, potentially fatal conditions. Medications to treat NAFLD/NASH are sorely needed.

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.

Prior to this study, the effect of empagliflozin, an oral SGLT-2 inhibitor, on human liver fat had not been evaluated. This study aimed to examine the effect of empagliflozin on liver fat in patients with type 2 diabetes and NAFLD, using MRI-derived proton density-fat fraction (MRI-PDFF) for liver fat quantification. MRI-PDFF is a robust, accurate and well-validated technique for measuring liver fat.

They randomly assigned patients to empagliflozin 10 mg plus their standard medical treatment for type 2 diabetes or standard medical treatment only.  At 20 weeks, the addition of empagliflozin yielded substantial reductions in liver fat, as measured by MRI-derived proton density fat fraction, with a mean difference of 4% between the two groups (P < .0001). End-of-treatment 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).

The researchers also observed a significant between-group difference in alanine aminotransferase (–10.9 IU/L, P = 0.005) and nonsignificant difference in aspartate aminotransferase (–7.7 IU/L; P = .212) and gamma-glutamyl transpeptidase (–11 IU/L; P = .057) over the study period.

The results showed that 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).  Also, 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). Plus 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)

The takeaway from the study is that 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 and the 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 and more research needs to be done.

Practice Pearls:

  • 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.

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