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Effect of Empagliflozin on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial (E-LIFT Trial)
Abstract
OBJECTIVE Sodium–glucose cotransporter 2 (SGLT-2) inhibitors have been shown to reduce liver fat in rodent models. Data regarding the effect of SGLT-2 inhibitors on human liver fat are scarce. This study examined the effect of empagliflozin (an SGLT-2 inhibitor) on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) by using MRI-derived proton density fat fraction (MRI-PDFF). RESEARCH DESIGN AND METHODS Fifty patients with type 2 diabetes and NAFLD were randomly assigned to either the empagliflozin group (standard treatment for type 2 diabetes plus empagliflozin 10 mg daily) or the control group (standard treatment without empagliflozin) for 20 weeks. Change in liver fat was measured by MRI-PDFF. Secondary outcome measures were change in alanine transaminase (ALT), aspartate transaminase (AST), and γ-glutamyl transferase (GGT) levels. RESULTS When included in the standard treatment for type 2 diabetes, empagliflozin was significantly better at reducing liver fat (mean MRI-PDFF difference between the empagliflozin and control groups −4.0%; P < 0.0001). Compared with baseline, significant reduction was found in the end-of-treatment MRI-PDFF for the empagliflozin group (16.2% to 11.3%; P < 0.0001) and a nonsignificant change was found in the control group (16.4% to 15.5%; P = 0.057). The two groups showed a significant difference for change in serum ALT level (P = 0.005) and nonsignificant differences for AST (P = 0.212) and GGT (P = 0.057) levels. CONCLUSIONS When included in the standard treatment for type 2 diabetes, empagliflozin reduces liver fat and improves ALT levels in patients with type 2 diabetes and NAFLD.
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“whereas both dapagliflozin and empagliflozin were able to reduce liver lipid content in people with type 2 diabetes with (dapagliflozin [153,154]) or both with and without MASLD (empagliflozin [98]).”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [153]
In the citing paper
“Trials in people with T2D (not all with MASLD and some excluding high ALT values) have shown a moderate reduction in liver lipid content with empagli fl ozin, 414,415 dapagli fl ozin 416 and licoglifl ozin.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [414]
In the citing paper
“Reductions in ALT were shown with empagli fl ozin 414 and licogli fl ozin.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [414]
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Metadata
- Authors
- Kuchay, M. S., Krishan, S., Mishra, S. K., Farooqui, K. J., Singh, M. K., Wasir, J. S., Bansal, B., Kaur, P., Jevalikar, G., Gill, H. K., Choudhary, N. S., & Mithal, A.
- Affiliations
- Medanta The Medicity (IN)
- Corresponding author
- Kuchay, Mohammad Shafi
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2018-06-12
- Volume
- 41
- Issue
- 8
- Pages
- 1801-1808
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2808615577
- Cited by
- 662
- References
- 40
- Citations by year
- 2026: 81 · 2025: 98 · 2024: 73 · 2023: 86 · 2022: 85 · 2021: 78 · 2020: 88 · 2019: 52 · 2018: 18
- FWCI
- 46.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Endocrine and Diabetes Foundation, India
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- empagliflozin, SGLT2 inhibitors, liver fat, non-alcoholic fatty liver disease, type 2 diabetes, proton density fat fraction, alanine aminotransferase, liver enzymes
- MeSH terms
- Adipose Tissue, Adult, Alanine Transaminase, Aspartate Aminotransferases, Benzhydryl Compounds, Diabetes Mellitus, Type 2, Female, Glucosides, Humans, Hypoglycemic Agents, Liver, Magnetic Resonance Imaging, Male, Middle Aged, Treatment Outcome, Adiposity, Non-alcoholic Fatty Liver Disease
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