Evidence map›Paper›PMID 39913634›Full record

Trial reportDiabetes care2025

Risk of Incident Diabetes Related to Lipoprotein(a), LDL Cholesterol, and Their Changes With Alirocumab: Post Hoc Analyses of the ODYSSEY OUTCOMES Randomized Trial.

Gregory G Schwartz, Michael Szarek, J Wouter Jukema, Christa M Cobbaert, Esther Reijnders, Vera A Bittner, Markus Schwertfeger, Deepak L Bhatt, Sergio Fazio, Genevieve Garon and 4 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes care, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01663402. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01663402 phase3completed

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Effect of Alirocumab (SAR236553/REGN727) on the Occurrence of Cardiovascular Events in Patients Who Have Recently Experienced an Acute Coronary Syndrome

Ran2012Enrolled18,924Registered outcomes15Posted comparisons6ConditionsAtherosclerotic Cardiovascular DiseaseArmsAlirocumab, LMT, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Lipoprotein (a) in primary cardiovascular disease prevention is actionable today.American heart journal plus : cardiology research and practice · 2025
    Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Gregory G SchwartzDivision of Cardiology, University of Colorado School of Medicine, Aurora, CO.ORCID 0000-0003-2954-0695
Michael SzarekDivision of Cardiology, University of Colorado School of Medicine, Aurora, CO.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Christa M CobbaertDepartment of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Esther ReijndersDepartment of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Vera A BittnerDivision of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL.
Markus SchwertfegerRoche Diagnostics International, Zug, Switzerland.
Deepak L BhattMount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY.
Sergio FazioRegeneron Pharmaceuticals, Tarrytown, NY.
Genevieve GaronSanofi, North York, Ontario, Canada.
Shaun G GoodmanCanadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
Robert A HarringtonWeill Cornell Medical College, New York, NY.
Harvey D WhiteGreen Lane Cardiovascular Research Unit, Te Whatu Ora-Health New Zealand and University of Auckland, Te Toka Tumai, New Zealand.
Philippe Gabriel StegUniversité Paris-Cité, INSERM-UMR1148, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, French Alliance for Cardiovascular Trials, Institut Universitaire de France, Paris, France.

Funding

Regeneron PharmaceuticalsRoche DiagnosticsSanofi
6 · The paper itself

Abstract

objectivePrevious genetic and clinical analyses have associated lower lipoprotein(a) and LDL cholesterol (LDL-C) with greater risk of new-onset type 2 diabetes (NOD). However, PCSK9 inhibitors such as alirocumab lower both lipoprotein(a) and LDL-C without effect on NOD. RESEARCH DESIGN AND

methodsIn a post hoc analysis of the ODYSSEY OUTCOMES trial (NCT01663402), we examined the joint prediction of NOD by baseline lipoprotein(a), LDL-C, and insulin (or HOMA-insulin resistance [HOMA-IR]) and their changes with alirocumab treatment. Analyses included 8,107 patients with recent acute coronary syndrome on optimized statin therapy, without diabetes at baseline, assigned to alirocumab or placebo with median follow-up 2.4 years. Splines were estimated from logistic regression models.

resultsLower baseline lipoprotein(a) and higher baseline insulin or HOMA-IR independently predicted 782 cases of NOD; baseline LDL-C did not predict NOD. Alirocumab reduced lipoprotein(a) and LDL-C without affecting insulin or NOD risk (odds ratio [OR] vs. placebo 0.998; 95% CI 0.860-1.158). However, in logistic regression, decreased lipoprotein(a) and LDL-C on alirocumab were independent, opposite predictors of NOD. OR for NOD for 25% and 50% lipoprotein(a) reductions on alirocumab were 1.12 (95% CI 1.01-1.23) and 1.24 (1.02-1.52). OR for NOD for 25% and 50% LDL-C reductions on alirocumab were 0.88 (95% CI 0.80-0.97) and 0.77 (0.64-0.94).

conclusionsBaseline lipoprotein(a) was inversely associated with risk of NOD. Alirocumab-induced reductions of lipoprotein(a) and LDL-C were associated with increased and decreased risk of NOD, respectively, without net effect on NOD. Ongoing trials will determine the impact of larger and longer lipoprotein(a) reductions on NOD.

Indexed as

Cholesterol, LDLDiabetes Mellitus, Type 2Lipoprotein(a)AgedAntibodies, Monoclonal, HumanizedFemaleHumansMaleMiddle AgedalirocumabAntibodies, Monoclonal, HumanizedCholesterol, LDLLipoprotein(a)

Identifiers

PMID39913634
PMCPMC11932820

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.