Evidence mapPaperPMID 33932126Full record

ReviewCPT: pharmacometrics & systems pharmacology2021

End-to-end application of model-informed drug development for ertugliflozin, a novel sodium-glucose cotransporter 2 inhibitor.

Daryl J Fediuk, Gianluca Nucci, Vikas K Dawra, Ernesto Callegari, Susan Zhou, Cynthia J Musante, Yali Liang, Kevin Sweeney, Vaishali Sahasrabudhe

Open access · goldAbstract readReview
In one paragraph

Review in CPT: pharmacometrics & systems pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 2 pooled it
1.2field-weighted citation impact, top 21% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Review
  6. Pharmacomicrobiomics.Clinical pharmacology and therapeutics · 2025
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. 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

9 authors at 2 institutions in 1 country.

Daryl J FediukPfizer Inc., Groton, Connecticut, USA.
Gianluca NucciPfizer Inc., Cambridge, Massachusetts, USA.
Vikas K DawraPfizer Inc., New York, New York, USA.
Ernesto CallegariPfizer Inc., Groton, Connecticut, USA.
Susan ZhouMerck & Co., Inc., Kenilworth, New Jersey, USA.
Cynthia J MusantePfizer Inc., Cambridge, Massachusetts, USA.
Yali LiangPfizer Inc., Groton, Connecticut, USA.
Kevin SweeneyPfizer Inc., Groton, Connecticut, USA.
Vaishali SahasrabudhePfizer Inc., Groton, Connecticut, USA.
Pfizer (United States) · USMerck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Model-informed drug development (MIDD) is critical in all stages of the drug-development process and almost all regulatory submissions for new agents incorporate some form of modeling and simulation. This review describes the MIDD approaches used in the end-to-end development of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor approved for the treatment of adults with type 2 diabetes mellitus. Approaches included (1) quantitative systems pharmacology modeling to predict dose-response relationships, (2) dose-response modeling and model-based meta-analysis for dose selection and efficacy comparisons, (3) population pharmacokinetics (PKs) modeling to characterize PKs and quantify population variability in PK parameters, (4) regression modeling to evaluate ertugliflozin dose-proportionality and the impact of uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A9 genotype on ertugliflozin PKs, and (5) physiologically-based PK modeling to assess the risk of UGT-mediated drug-drug interactions. These end-to-end MIDD approaches for ertugliflozin facilitated decision making, resulted in time/cost savings, and supported registration and labeling.

Indexed as

Models, BiologicalBridged Bicyclo Compounds, HeterocyclicDiabetes Mellitus, Type 2Dose-Response Relationship, DrugDrug DevelopmentHumansNetwork PharmacologyRegression AnalysisSodium-Glucose Transporter 2 InhibitorsBridged Bicyclo Compounds, HeterocyclicertugliflozinSodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID33932126
PMCPMC8213419
OpenAlexW3159771686

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.