Dulaglutide decreases plasma aminotransferases in people with Type 2 diabetes in a pattern consistent with liver fat reduction: a <i>post hoc</i> analysis of the <scp>AWARD</scp> programme
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Bibliographic record
Abstract
Abstract Aims To evaluate the effects of dulaglutide vs placebo on liver and glycaemic/metabolic measurements in a population with Type 2 diabetes and in a subgroup with non‐alcoholic fatty liver/non‐alcoholic steatohepatitis. Methods A total of 1499 participants from AWARD ‐1, AWARD ‐5, AWARD ‐8 and AWARD ‐9 clinical trials were included in this analysis (dulaglutide 1.5 mg, n =971 and placebo, n =528). Thresholds of alanine aminotransferase levels ≥30 IU /l in men and ≥19 IU /l in women were used to determine the subgroup who had non‐alcoholic fatty liver/non‐alcoholic steatohepatitis. Objectives included changes from baseline to 6 months in: (1) alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase levels in the overall population and (2) alanine aminotransferase, aspartate transaminase, gamma‐glutamyl transpeptidase and glycaemic/metabolic measurements (e.g. HbA 1c , fasting serum glucose, body weight, lipids and homeostatic model assessment) in the non‐alcoholic fatty liver/non‐alcoholic steatohepatitis subgroup. Results In the overall population at 6 months, dulaglutide significantly reduced alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase levels vs placebo [least squares mean treatment differences: –1.7 IU /l (95% CI –2.8, –0.6), P =0.003; –1.1 IU /l (95% CI –2.1, –0.1), P =0.037; –6.6 IU /l (95% CI –12.4, –0.8), P =0.025, respectively]. In the subgroup with non‐alcoholic fatty liver/non‐alcoholic steatohepatitis (alanine aminotransferase levels greater than or equal to the upper limit of normal), mean baseline liver enzyme values were 38.0 IU /l, 27.8 IU /l and 43.9 IU /l for alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase, respectively. In this population, more pronounced reductions from baseline in alanine aminotransferase were observed with dulaglutide vs placebo (–8.8 IU /l vs –6.7 IU /l). In the subgroup of people with alanine aminotransferase levels less than the upper limit of normal, changes from baseline in alanine aminotransferase did not significantly differ between treatment groups (0.0 IU /l vs 0.7 IU /l). Conclusions Once‐weekly dulaglutide improved alanine aminotransferase, aspartate transaminase and gamma‐glutamyl transpeptidase levels compared with placebo in a pattern consistent with liver fat reductions. Our results add further weight to the notion that glucagon‐like peptide‐1 receptor agonists may provide benefit in lowering liver fat in addition to their other metabolic actions.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it