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Randomized Controlled Trial
. 2024 Apr 1;47(4):668-675.
doi: 10.2337/dc23-1646.

Empagliflozin Reduces Liver Fat in Individuals With and Without Diabetes

Siham Abdelgani  1 , Ahmed Khattab  1 , John Adams  1 , Gozde Baskoy  1 , Marissa Brown  1 , Geoff Clarke  1 , Olga Larvenenko  1 , Ralph A DeFronzo  1 , Muhammad Abdul-Ghani  1
Affiliations
Randomized Controlled Trial

Empagliflozin Reduces Liver Fat in Individuals With and Without Diabetes

Siham Abdelgani et al. Diabetes Care. .

Abstract

Objective: To examine the effect of empagliflozin on liver fat content in individuals with and without type 2 diabetes (T2D) and the relationship between the decrease in liver fat and other metabolic actions of empagliflozin.

Research design and methods: Thirty individuals with T2D and 27 without were randomly assigned to receive in double-blind fashion empagliflozin or matching placebo (2:1 ratio) for 12 weeks. Participants underwent 75-g oral glucose tolerance testing and measurement of liver fat content with MRS before therapy and at study end. Hepatic glucose production before the start of therapy was measured with 3-3H-glucose.

Results: Empagliflozin caused an absolute reduction of 2.39% ± 0.79% in liver fat content compared with an increase of 0.91% ± 0.64% in participants receiving placebo (P < 0.007 with ANOVA). The decrease in liver fat was comparable in both individuals with diabetes and those without (2.75% ± 0.81% and 1.93% ± 0.78%, respectively; P = NS). The decrease in hepatic fat content caused by empagliflozin was strongly correlated with baseline liver fat content (r = -0.62; P < 0.001), decrease in body weight (r = 0.53; P < 0.001), and improvement in insulin sensitivity (r = -0.51; P < 0.001) but was not related to the decrease in fasting plasma glucose or HbA1c or the increase in hepatic glucose production.

Conclusions: Empagliflozin is effective in reducing liver fat content in individuals with and without T2D. The decrease in liver fat content is independent of the decrease in plasma glucose concentration and is strongly related to the decrease in body weight and improvement in insulin sensitivity.

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Conflict of interest statement

Duality of Interest. R.A.D. receives grant support from AstraZeneca and Merck; is a member of the advisory boards of AstraZeneca, Intarcia, Boehringer Ingelheim, Renalytix, and Novo Nordisk; and is a member of the AstraZeneca speakers’ bureaus. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
A: Absolute change in liver fat content (LFC; %) in patients with T2D and in individuals without diabetes receiving empagliflozin (EMPA) or placebo (PLC). B: Relationship between the decrease in hepatic fat content and baseline liver fat in patients with T2D and in individuals without diabetes. Open circles represent individuals without diabetes, and closed circles represent patients with T2D. C: Decrease in LFC in participants with baseline LFC >7% (in patients with T2D [n = 11] and those without diabetes [n = 11]) and in participants with baseline liver fat <7% (n = 9 and n = 7, respectively). Asterisks represent statistical significance as follows: *P < 0.05, **P < 0.01.
Figure 2
Figure 2
A: Relationship between the absolute change from baseline to week 12 in hepatic fat content in participants receiving empagliflozin (n = 38; closed circles) and placebo (n = 19; open circles) and percentage decrease in body weight (r = 0.52; P < 0.001). B: Increase in the Matsuda index of insulin sensitivity (r = −0.51; P < 0.001). C: Change in the insulin clearance rate (r = −0.46; P < 0.01).
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