Exenatide and dapagliflozin combination improves markers of liver steatosis and fibrosis in patients with type 2 diabetes.

Authors

• Amalia Gastaldelli
• Enrico Repetto
• Cristian Guja
• Elise Hardy
• Jenny Han
• Serge A Jabbour
• Ele Ferrannini

Publication/Presentation Date

3-1-2020

Abstract

AIM: To assess the efficacy of exenatide (EXE) once weekly + dapagliflozin once daily (DAPA) versus each drug alone in reducing biomarkers of fatty liver/steatosis and fibrosis in a post hoc analysis of DURATION-8, a 104-week study in 695 patients with type 2 diabetes uncontrolled by metformin monotherapy.

MATERIALS AND METHODS: We evaluated the impact of the study treatments on non-invasive markers of hepatic steatosis (fatty liver index [FLI] and non-alcoholic fatty liver disease [NAFLD] liver fat score), fibrosis (fibrosis-4 index [FIB-4]) and severe fibrosis (NAFLD fibrosis score), along with liver enzymes and insulin resistance, at weeks 28 and 52. All outcomes in this analysis were exploratory, with nominal P values reported.

RESULTS: At week 28, biomarkers of fatty liver/steatosis and fibrosis were reduced from baseline in all treatment groups. At week 28, EXE once weekly + DAPA effects for decrease in FLI were stronger than those of EXE once weekly + placebo (PLB; -2.92, 95% confidence interval [CI] -5.11, -0.73; P = 0.0092) or DAPA+PLB (-2.77 [95% CI -4.93, -0.62]; P = 0.0119), and stronger than those of EXE once weekly + PLB at week 52 (-3.23 [95% CI -5.79, -0.68]; P = 0.0134). FIB-4 showed reduction versus baseline only in the EXE once weekly + DAPA group at both week 28 (-0.06 [95% CI -0.11, -0.01]; P = 0.0135) and week 52 (-0.05 [95% CI -0.09, -0.004]; P = 0.0308).

CONCLUSIONS: The EXE once weekly + DAPA combination showed stronger effects than EXE once weekly + PLB or DAPA + PLB in ameliorating markers of hepatic steatosis and fibrosis in patients with type 2 diabetes. Prospective trials are needed to validate these findings.

Volume

22

Issue

3

First Page

393

Last Page

403

ISSN

1463-1326

Published In/Presented At

Gastaldelli, A., Repetto, E., Guja, C., Hardy, E., Han, J., Jabbour, S. A., & Ferrannini, E. (2020). Exenatide and dapagliflozin combination improves markers of liver steatosis and fibrosis in patients with type 2 diabetes. Diabetes, obesity & metabolism, 22(3), 393–403. https://doi.org/10.1111/dom.13907

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

31692226

Department(s)

Administration and Leadership

Document Type

Article