Evidence mapPaperPMID 32314505Full record

ArticleDiabetes, obesity & metabolism2020

A glycosylated Fc-fused glucagon-like peptide-1 receptor agonist exhibits equivalent glucose lowering to but fewer gastrointestinal side effects than dulaglutide.

In Bok An, Mi Sun Byun, Sang In Yang, Yuri Choi, Jung Won Woo, Hak Chul Jang, Young Chul Sung

Open access · hybridAbstract readClinical Trial, Phase I
In one paragraph

Article in Diabetes, obesity & metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

1 citing paper in PubMed, 7 citations in OpenAlex.

  1. Article
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

7 authors at 3 institutions in 1 country.

In Bok AnSeoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Republic of Korea.ORCID 0000-0001-8156-469X
Mi Sun ByunResearch Institute, Genexine Co. Ltd., Seongnam, Republic of Korea.
Sang In YangResearch Institute, Genexine Co. Ltd., Seongnam, Republic of Korea.
Yuri ChoiResearch Institute, Genexine Co. Ltd., Seongnam, Republic of Korea.
Jung Won WooResearch Institute, Genexine Co. Ltd., Seongnam, Republic of Korea.
Hak Chul JangSeoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, Republic of Korea.
Young Chul SungResearch Institute, Genexine Co. Ltd., Seongnam, Republic of Korea.
Genexine (South Korea) · KRSeoul National University Bundang Hospital · KRPohang University of Science and Technology · KR

Funding

Korea Ministry of Health and Welfare HI14C1024Korea Ministry of Health and Welfare HI17C0643
6 · The paper itself

Abstract

aimTo evaluate the pharmacokinetic and pharmacodynamic properties of a novel glycosylated Fc-fused glucagon-like peptide-1(GLP-1-gFc) receptor agonist with distinctive receptor binding affinity, designed to improve in vivo stability and safety relative to the commercial GLP-1 analogue dulaglutide, and assess its safety profile and pharmacokinetics in healthy humans. MATERIALS AND

methodsWe constructed GLP-1-gFc and determined its binding affinity and potency using in vitro instrumental and cell-based analyses followed by in vivo comparison of the glucose-lowering and gastrointestinal side effects between GLP-1-gFc and dulaglutide. A phase 1 clinical trial was conducted to confirm the efficacy and safety profile of GLP-1-gFc.

resultsGLP-1-gFc showed 10-fold less binding affinity and 4-fold less potency than dulaglutide in in vitro. A potency-adjusted dose delayed HbA1c increase comparable with that of dulaglutide (Change for 6 weeks: 2.4 mg/kg GLP-1-gFc, 4.34 ± 0.40 vs. 0.6 mg/kg dulaglutide, 4.26 ± 0.22; n.s.). However, the equivalent efficacy dose and higher dose did not induce malaise-related responses (blueberry bar consumption, g/mouse: 2.4 mg/kg GLP-1-gFc, 0.15% ± 0.03% vs. 0.6 mg/kg dulaglutide, 0.04% ± 0.01%; P < .01) or QT interval changes (mean at 14-20 hours, mSc: 0.28 mg/kg GLP-1-gFc, 0.0-8.0 vs. 0.07 mg/kg dulaglutide, 8.0-27.7; n.s.), observed as safety variables in rats and monkeys, compared with those of dulaglutide. Glucose reductions in an oral glucose tolerance test were significant at day 3 postdose without severe gastrointestinal adverse events and pulse rate changes in healthy subjects.

conclusionsThese results suggest that GLP-1-gFc could be used as a novel GLP-1 receptor agonist with better safety than dulaglutide to maximize therapeutic benefits in subjects with type 2 diabetes.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 ReceptorAnimalsBlood GlucoseGlucagon-Like PeptidesGlucoseGlycated HemoglobinHumansHypoglycemic AgentsImmunoglobulin Fc FragmentsMiceRatsRecombinant Fusion ProteinsBlood GlucosedulaglutideGlucagon-Like Peptide-1 ReceptorGlucagon-Like PeptidesGlucoseGlycated HemoglobinHypoglycemic AgentsImmunoglobulin Fc FragmentsRecombinant Fusion Proteinsdrug development, dulaglutide, GLP-1 analogue, glycaemic control, type 2 diabetes

Identifiers

PMID32314505
PMCPMC7383507
OpenAlexW3016365084

What Socratic holds

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Registered trials

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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.