Inclisiran in individuals with diabetes or obesity: Post hoc pooled analyses of the <scp>ORION</scp> ‐9, <scp>ORION</scp> ‐10 and <scp>ORION</scp> ‐11 Phase 3 randomized trials
Bibliographic record
Abstract
Abstract Aims To conduct a pooled analysis of Phase 3 trials investigating the efficacy and safety of inclisiran across glycaemic and body mass index (BMI) strata. Materials and Methods Participants were randomized 1:1 to receive 300 mg inclisiran sodium or placebo twice yearly, after initial and 3‐month doses up to 18 months, with background oral lipid‐lowering therapy. Analyses were stratified by glycaemic status (normoglycaemia, prediabetes, and diabetes) or BMI (<25, ≥25 to <30, ≥30 to <35, and ≥35 kg/m 2 ). Co‐primary endpoints were percentage and time‐adjusted percentage change in low‐density lipoprotein (LDL) cholesterol from baseline. Safety was also assessed. Results Baseline characteristics were balanced between treatment arms and across strata. Percent LDL cholesterol change (placebo‐corrected) with inclisiran from baseline to Day 510 ranged from −47.6% to −51.9% and from −48.8% to −54.4% across glycaemic/BMI strata, respectively. Similarly, time‐adjusted percentage changes after Day 90 and up to Day 540 ranged from −46.8% to −52.0% and from −48.6% to −53.3% across glycaemic/BMI strata, respectively. Inclisiran led to significant reductions in proprotein convertase subtilisin/kexin type 9 and other atherogenic lipids and lipoproteins versus placebo across the glycaemic/BMI strata. The proportions of individuals achieving LDL cholesterol thresholds of <1.8 mmol/L and <1.4 mmol/L with inclisiran increased with increasing glycaemic and BMI strata. Across the glycaemic/BMI strata, a higher proportion of individuals had mild/moderate treatment‐emergent adverse events (TEAEs) at the injection site with inclisiran (2.8%–7.7%) versus placebo (0.2%–2.1%). Conclusion Inclisiran provided substantial and sustained LDL cholesterol lowering across glycaemic/BMI strata, with a modest excess of transient mild‐to‐moderate TEAEs at the injection site.
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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 | 0.007 | 0.011 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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; both teacher heads agree on what is shown here.
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".