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).
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.
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.
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.
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.
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The dataset for the current study is available on reasonable request by contacting MSK.
The Assessment of Weekly Administration of Dulaglutide in Diabetes
Controlled attenuation parameter
Effect of dulaglutide on liver fat
Dipeptidyl peptidase 4
Fasting plasma glucose
Glucagon-like peptide-1 receptor
Liver fat content
Liver stiffness measurement
MRI-estimated proton density fat fraction
Non-alcoholic fatty liver disease
Pancreatic fat fraction
Region of interest
Vibration-controlled transient elastography
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We want to thank S. Rao (research coordinator, Division of Endocrinology and Metabolism, Medanta–The Medicity Hospital, Gurugram) for his help in the conduct of the study. We also want to thank the Endocrine and Diabetes foundation (EDF), India for providing a grant for this study.
Authors’ relationships and activities
MSK has received speaker honoraria from Novartis, Sanofi, Wockhardt Limited, AstraZeneca and Novo Nordisk. SKM has received speaker honoraria from Sanofi, Novartis, AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Lupin Limited and Abbott India Limited. JSW has received speaker honoraria from Boehringer Ingelheim, Novartis, Sanofi, Abbott India Limited, Wockhardt Limited, AstraZeneca and Novo Nordisk. AM has received speaker honoraria from Johnson and Johnson, Amgen, Sanofi, Novartis, AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Lupin Limited and Abbott India Limited. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.
The current study was supported by an investigator-initiated study grant to MSK from Medanta–The Medicity’s departmental research fund and a grant from the Endocrine and Diabetes Foundation (EDF), India. The funding agency did not have any role in the design and conduct of the study, collection, management, analysis or interpretation of the data, or in the preparation, review or approval of the manuscript.
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Kuchay, M.S., Krishan, S., Mishra, S.K. et al. Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial). Diabetologia 63, 2434–2445 (2020). https://doi.org/10.1007/s00125-020-05265-7
- Controlled attenuation parameter
- GLP-1 receptor agonists
- Liver stiffness measurement
- MRI-derived proton density fat fraction
- Non-alcoholic fatty liver disease
- Non-alcoholic steatohepatitis
- Pancreatic fat content