Abstract 4139912: Inflammatory biomarkers in people treated with tirzepatide living with overweight or obesity, without and with T2D: a post-hoc analysis from SURMOUNT-1 and SURMOUNT-2
Bibliographic record
Abstract
Background: Tirzepatide (TZP) is a once weekly GIP and GLP-1 receptor agonist approved for the treatment of type 2 diabetes (T2D) and obesity. This post hoc analysis examined biomarkers of inflammation in people living with obesity, or overweight, without and with T2D, from SURMOUNT-1 and SURMOUNT-2. Furthermore, we evaluated the contribution of weight reduction- associated and - unassociated effects on biomarkers of inflammation. Methods: A total of 700 participants were randomly selected from SURMOUNT-1 and SURMOUNT-2 (100 participants from each treatment arm: placebo, 5, 10, and 15 mg in SURMOUNT-1 and placebo, 10 and 15 mg in SURMOUNT-2). The association of treatment with change from baseline in the inflammation biomarkers interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP) at 24 and 72 weeks was assessed along with the estimated percentages of the association attributable to weight loss through a mediation analysis. Results: In SURMOUNT-1, following 72 weeks of treatment with TZP without T2D, TZP was associated with significantly decreased IL-6 (-26% to -31%) and hsCRP (-51% to -65%), compared to placebo in all dose groups. In SURMOUNT-2, following 72 weeks of treatment with TZP in participants with T2D, changes of -16% to -23% in IL-6 and -55% to -56% in hsCRP were observed (significance seen for all groups except for TZP 15mg on IL-6). At 24 weeks, only 18% and 31% of hsCRP changes were associated with weight reduction in SURMOUNT-1 and -2, respectively. In SURMOUNT-1, 77% of IL-6 changes and 87% of hsCRP changes at 72 weeks were associated with weight reduction. In SURMOUNT-2, 78% of IL-6 changes and 57% of hsCRP changes at 72 weeks were associated with body weight reduction. Conclusions: In this post hoc analysis of SURMOUNT-1 and -2, early changes in hsCRP (week 24) were weight reduction-unassociated, while at week 72, changes in the inflammation biomarkers IL-6 and hsCRP observed in TZP-treated participants were mainly weight reduction-associated. The relative contribution of weight reduction-dependent effects was more prominent in participants without T2D, compared to those with T2D. Collectively, these data suggest TZP was associated with reduced inflammation in people with overweight/obesity and/or T2D.
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How this classification was reachedexpand
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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".