Empagliflozin Reduces Liver Fat Content Regardless of T2DM, Study Finds

Siham Abdelgani, MD, MPH

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Empagliflozin is equally effective for reducing liver fat content in patients with type 2 diabetes mellitus (T2DM) and in nondiabetic individuals, according to findings from a double-blind randomized trial.

Results presented at The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD) in Boston this weekend by Siham Abdelgani, MD, MPH, of the University of Texas at San Antonio, showed decreases in liver fat content were independent of changes in plasma glucose concentration but were associated with decreased body weight and improvement in insulin sensitivity.¹

Since initial approval in 2014 for the treatment of T2DM, empafgliflozin has carved a role for itself in the management of cardiometabolic conditions. This has culminated in additional approvals for treating heart failure, reducing cardiovascular death in adults with T2DM, and, its most recent approval in September 2023, for treating chronic kidney disease.²

The present study was not the only research about treating fatty liver presented in Boston this weekend. An additional analysis of a recent 48-week, phase 2 obesity trial of retatrutide was also presented at The Liver Meeting, with data showing the novel triple agonist therapy was effective for reducing liver fat in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

To examine the effect of empagliflozin on liver fat content and the relationship between the decrease in liver fat and other metabolic actions of empagliflozin, investigators randomly assigned 57 patients in a 2:1 ratio to receive treatment with empagliflozin or matching placebo. Among the cohort, 30 participants had T2DM and 27 were nondiabetic.¹

Patients received 75 g oral glucose tolerance tests and liver fat content was measured with MRI spectroscopy before and at the end of therapy. Hepatic glucose production at the start of therapy was measured with 3H-glucose infusion.¹

Among participants with T2DM, treatment with empagliflozin caused -2.75% absolute reduction in liver fat content compared to -1.93% among those without diabetes. Patients with T2DM who received placebo experienced +0.9% absolute change in liver fat content. Investigators pointed out nondiabetic participants in the placebo group experienced a similar result with a +0.8% increase in liver fat content (P < .05 for both groups).¹

Upon analysis, the decrease in hepatic fat content was strongly influenced by baseline liver fat content and was related to the decrease in body weight (r = 0.53; P < .001) and improvement in insulin sensitivity caused by empagliflozin (r = -0.51; P < .001). However, investigators noted the decrease in hepatic fat content was not influenced by the decrease in fasting plasma glucose, HbA1c, or the increase in hepatic glucose production.¹

“Empagliflozin is equally effective in reducing liver fat content in T2DM patients and in nondiabetic individuals. The decrease in liver fat content is independent of the decrease in plasma glucose concentration but is strongly related to the decrease in body weight and improvement in insulin sensitivity,” concluded investigators.¹

References:

1. Abdelgani S, et al. 151: EMPAGLIFLOZIN IS EQUALLY EFFECTIVE IN REDUCING LIVER FAT CONTENT IN T2DM PATIENTS AND IN NON-DIABETIC INDIVIDUALS, A RANDOMIZED TRIAL. Paper presented at: The Liver Meeting. Boston, MA. November 10 - 14, 2023.
2. Stewart G. Jardiance FDA Approval History. FDA History. September 24, 2023. Accessed November 15, 2023. https://www.drugs.com/history/jardiance.html