Add-on dulaglutide may reduce liver fat in people with type 2 diabetes, NAFLD
medwireNews: Results from the D-LIFT trial suggest a reduction in liver fat content (LFC) when dulaglutide, a glucagon-like peptide (GLP)-1 receptor agonist, is added to standard care treatment in people with concurrent type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).
The placebo-controlled study was conducted in India and included 52 adults with type 2 diabetes and LFC of at least 6.0% at baseline, as assessed by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). They were randomly assigned to receive dulaglutide weekly for 24 weeks (0.75 mg for 4 weeks and 1.5 mg thereafter) added to standard care, or standard care only.
As reported in Diabetologia, average LFC decreased from 17.9% at baseline to 12.0% at week 24 in the dulaglutide group and from 17.1% to 14.8% in the control arm. The absolute LFC reduction was significantly higher in the dulaglutide versus the control arm (5.8 vs 2.3%), as was the relative LFC change (32.1 vs 5.7%).
Moreover, after 24 weeks, 26% of the dulaglutide-treated patients reached an LFC below 6.0% on MRI-PDFF, compared with just 8% of those in the control group.
Moreover, Mohammad Kuchay (Medanta–The Medicity Hospital, Haryana, India) and fellow researchers report that dulaglutide-treated patients had a significantly greater reduction in serum γ-glutamyl transpeptidase (GGT) levels from baseline to week 24, with an average between-group difference of 13.1 U/L. There was also a trend toward a larger reduction in aspartate aminotransferase and alanine aminotransferase levels when comparing the dulaglutide and control groups, but the between-group difference did not reach statistical significance.
There were no significant between-group differences in the reduction in pancreatic fat content and liver stiffness from baseline to week 24.
Participants in both treatment groups experienced a significant reduction in average fasting plasma glucose (FPG) and HbA1c levels, with comparable reductions in the two arms. In patients treated with dulaglutide FPG fell from 9.9 to 6.3 mmol/L (178.4 to 113.6 mg/dL), and HbA1c fell from 69 to 51 mmol/mol (8.5 to 6.8%); in the control group FPG fell from 9.5 to 6.9 mmol/L (171.2 to 124.4 mg/dL) and HbA1c fell from 68 mmol/mol to 54 mmol/mol (8.4 to 7.1%).
The researchers also report a significant reduction in bodyweight among patients treated with dulaglutide compared with the control group. Noting that “[b]ody weight reduction is a class effect of all GLP-1 [receptor] agonists,” they say that this “was a significant factor driving the decrease in LFC following dulaglutide treatment in our study.”
The team concludes: “There is a huge unmet need for a NAFLD treatment; dulaglutide could assist by reducing liver fat and improving liver enzymes in patients with coexisting type 2 diabetes and NAFLD.”
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