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31.08.2020 | Article

Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial)

verfasst von: Mohammad S. Kuchay, Sonal Krishan, Sunil K. Mishra, Narendra S. Choudhary, Manish K. Singh, Jasjeet S. Wasir, Parjeet Kaur, Harmandeep K. Gill, Tarannum Bano, Khalid J. Farooqui, Ambrish Mithal

Erschienen in: Diabetologia | Ausgabe 11/2020

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Abstract

Aims/hypothesis

Liraglutide, a daily injectable glucagon-like peptide-1 receptor (GLP-1r) agonist, has been shown to reduce liver fat content (LFC) in humans. Data regarding the effect of dulaglutide, a once-weekly GLP-1r agonist, on human LFC are scarce. This study examined the effect of dulaglutide on LFC in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).

Methods

Effect of dulaglutide on liver fat (D-LIFT) was a 24 week, open-label, parallel-group, randomised controlled trial to determine the effect of dulaglutide on liver fat at a tertiary care centre in India. Adults (n = 64), who had type 2 diabetes and MRI-derived proton density fat fraction-assessed LFC of ≥6.0% at baseline, were randomly assigned to receive dulaglutide weekly for 24 weeks (add-on to usual care) or usual care, based on a predefined computer-generated number with a 1:1 allocation that was concealed using serially numbered, opaque, sealed envelopes. The primary endpoint was the difference of the change in LFC from 0 (baseline) to 24 weeks between groups. The secondary outcome measures included the difference of the change in pancreatic fat content (PFC), change in liver stiffness measurement (LSM in kPa) measured by vibration-controlled transient elastography, and change in liver enzymes.

Results

Eighty-eight patients were screened; 32 were randomly assigned to the dulaglutide group and 32 to the control group. Overall, 52 participants were included for per-protocol analysis: those who had MRI-PDFF data at baseline and week 24. Dulaglutide treatment resulted in a control-corrected absolute change in LFC of −3.5% (95% CI −6.6, −0.4; p = 0.025) and relative change of −26.4% (−44.2, −8.6; p = 0.004), corresponding to a 2.6-fold greater reduction. Dulaglutide-treated participants also showed a significant reduction in γ-glutamyl transpeptidase (GGT) levels (mean between-group difference −13.1 U/l [95% CI −24.4, −1.8]; p = 0.025) and non-significant reductions in aspartate aminotransferase (AST) (−9.3 U/l [−19.5, 1.0]; p = 0.075) and alanine aminotransferase (ALT) levels (−13.1 U/l [−24.4, 2.5]; p = 0.10). Absolute changes in PFC (−1.4% [−3.2, 0.3]; p = 0.106) and LSM (−1.31 kPa [−2.99, 0.37]; p = 0.123) were not significant when comparing the two groups. There were no serious drug-related adverse events.

Conclusions/interpretation

When included in the standard treatment for type 2 diabetes, dulaglutide significantly reduces LFC and improves GGT levels in participants with NAFLD. There were non-significant reductions in PFC, liver stiffness, serum AST and serum ALT levels. Dulaglutide could be considered for the early treatment of NAFLD in patients with type 2 diabetes.

Trial registration

ClinicalTrials.gov NCT03590626

Funding

The current study was supported by an investigator-initiated study grant from Medanta–The Medicity’s departmental research fund and a grant from the Endocrine and Diabetes Foundation (EDF), India.

Graphical abstract

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Titel: Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial)
verfasst von: Mohammad S. Kuchay
Sonal Krishan
Sunil K. Mishra
Narendra S. Choudhary
Manish K. Singh
Jasjeet S. Wasir
Parjeet Kaur
Harmandeep K. Gill
Tarannum Bano
Khalid J. Farooqui
Ambrish Mithal
Publikationsdatum: 31.08.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 11/2020
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-020-05265-7

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