Evidence map›Paper›PMID 37700637›Full record

ArticleThe Journal of clinical endocrinology and metabolism2024

Tirzepatide Immunogenicity on Pharmacokinetics, Efficacy, and Safety: Analysis of Data From Phase 3 Studies.

Garrett R Mullins, Michael E Hodsdon, Ying Grace Li, Greg Anglin, Shweta Urva, Karen Schneck, Jennifer N Bardos, Ricardo Fonseca Martins, Katelyn Brown, Boris Calderon

Open access · hybridAbstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

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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

10 authors at 1 institution in 1 country.

Garrett R MullinsEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Michael E HodsdonEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Ying Grace LiEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Greg AnglinEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Shweta UrvaEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Karen SchneckEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Jennifer N BardosEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Ricardo Fonseca MartinsEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Katelyn BrownEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Boris CalderonEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.ORCID 0000-0003-1575-0739
Eli Lilly (United States) · US

Funding

Eli Lilly and Company.
6 · The paper itself

Abstract

contextAntidrug antibodies (ADA) can potentially affect drug pharmacokinetics, safety, and efficacy.

objectiveThis work aimed to evaluate treatment-emergent (TE) ADA in tirzepatide (TZP)-treated participants across 7 phase 3 trials and their potential effect on pharmacokinetics, efficacy, and safety.

methodsADA were assessed at baseline and throughout the study until end point, defined as week 40 (SURPASS-1, -2, and -5) or week 52 (SURPASS-3, -4, Japan-Mono, and Japan-Combo). Samples for ADA characterization were collected at SURPASS trial sites. Participants included ADA-evaluable TZP-treated patients with type 2 diabetes (N = 5025). Interventions included TZP 5, 10, or 15 mg. ADA were detected and characterized for their ability to cross-react with native glucose-dependent insulinotropic polypeptide (nGIP) and glucagon-like peptide-1 (nGLP-1), neutralize tirzepatide activity on GIP and GLP-1 receptors, and neutralize nGIP and nGLP-1.

resultsTE ADA developed in 51.1% of tirzepatide-treated patients. Proportions were similar across dose groups. Maximum ADA titers ranged from 1:20 to 1: 81 920 among TE ADA+ patients. Neutralizing antibodies (NAb) against TZP activity on GIP and GLP-1 receptors were observed in 1.9% and 2.1% of patients, respectively. Less than 1.0% of patients had cross-reactive NAb against nGIP or nGLP-1. TE ADA status, ADA titer, and NAb status had no effect on the pharmacokinetics or efficacy of TZP. More TE ADA+ patients experienced hypersensitivity reactions or injection site reactions than TE ADA- patients. The majority of hypersensitivity and injection site reactions were nonserious and nonsevere, and most events occurred and/or resolved irrespective of TE ADA status or titer.

conclusionImmunogenicity did not affect TZP pharmacokinetics or efficacy. The majority of hypersensitivity or injection site reactions experienced by TE ADA+ patients were mild to moderate in severity.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-2 ReceptorAntibodies, NeutralizingGastric Inhibitory PolypeptideGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorHumansHypoglycemic AgentsInjection Site ReactionTirzepatideAntibodies, NeutralizingGastric Inhibitory PolypeptideGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-2 ReceptorHypoglycemic AgentsTirzepatideclinical trialimmunogenicityincretin therapytype 2 diabetes

Identifiers

PMID37700637
PMCPMC10795913
OpenAlexW4386694437

What Socratic holds

Texttitle and abstract
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.