Evidence map›Paper›PMID 20739378›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2010

Piragliatin (RO4389620), a novel glucokinase activator, lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus: a mechanistic study.

Riccardo C Bonadonna, Tim Heise, Christophe Arbet-Engels, Christoph Kapitza, Angelo Avogaro, Joe Grimsby, Jay Zhi, Joseph F Grippo, Raffaella Balena

2 registry-linked trialsOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
16.6field-weighted citation impact, top 1% 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.

NCT04271189 phase3completedstarted 2020, after this paper: background citation

A Prospective, Randomized, Parallel-group, Adaptive Design Phase IIb/III, Multicenter Study, to Assess the Efficacy of Polychemotherapy for Inducing Remission of Newly Diagnosed Type 2 Diabetes.

Ran2020Enrolled108Registered outcomes10Posted comparisons0ConditionsNewly Diagnosed Type 2 DiabetesArmsMetformin-Sitagliptin-Empaglifozin-Pioglitazone, Standard of care
Open the trial in the graph
NCT04379726 unknown statusnot on this mapstarted 2020, after this paper: background citation

Characterization of β-cell Function and Insulin Sensitivity in Pre-transplant Patients With Cystic Fibrosis

TypeobservationalSponsorFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoRan2020 to 2023Enrolled150ConditionsCystic Fibrosis-related DiabetesArmstherapeutic optimization
3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 143 citations in OpenAlex.

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  15. Metabolic control analysis of hepatic glycogen synthesis in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2020
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  17. Antibacterial photosensitization through activation of coproporphyrinogen oxidase.Proceedings of the National Academy of Sciences of the United States of America · 2017
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Riccardo C BonadonnaDivision of Endocrinology and Metabolism, Department of Medicine, University of Verona School of Medicine, Verona, Italy. riccardo.bonadonna@tiscali.it
Tim Heise
Christophe Arbet-Engels
Christoph Kapitza
Angelo Avogaro
Joe Grimsby
Jay Zhi
Joseph F Grippo
Raffaella Balena
University of Padua · ITRoche (Switzerland) · CHUniversity of Verona · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

contextGlucokinase plays a key role in glucose homeostasis. Glucokinase activators can lower glucose levels in both animal and human type 2 diabetes, but their mechanism of action has never been explored in humans.

objectiveThe objective of the study was to investigate the effects of the glucokinase activator piragliatin (RO4389620) on β-cell function and glucose fluxes in both fasting and fed (oral glucose tolerance test) states in patients with type 2 diabetes.

designThis was a phase Ib randomized, double-blind, placebo-controlled crossover trial of two (25 and 100 mg) doses of piragliatin.

settingThis study was conducted at a clinical research center. PATIENTS: Patients included 15 volunteer ambulatory patients with mild type 2 diabetes.

interventionsInterventions included three 10-h (-300' to +300') studies, with an interval of at least 14 d. Administration of a single dose of placebo or piragliatin 25 mg or piragliatin 100 mg at -120'. Oral glucose tolerance test (at 0') with dual (iv and oral routes) tracer dilution technique was conducted.

main outcome measuresThe primary measure was plasma glucose concentration. The secondary measure was model assessed β-cell function and tracer-determined glucose fluxes.

resultsPiragliatin caused a dose-dependent reduction of glucose levels in both fasting and fed states (P < 0.01). In the fasting state, piragliatin caused a dose-dependent increase in β-cell function, a fall in endogenous glucose output, and a rise in glucose use (all P < 0.01). In the fed state, the primary effects of piragliatin were on β-cell function (P < 0.01).

conclusionsThe glucokinase activator piragliatin has an acute glucose-lowering action in patients with mild type 2 diabetes, mainly mediated through a generalized enhancement of β-cell function and through fasting restricted changes in glucose turnover.

Indexed as

Analysis of VarianceBenzeneacetamidesBlood GlucoseC-PeptideCross-Over StudiesDiabetes Mellitus, Type 2Dose-Response Relationship, DrugDouble-Blind MethodGlucokinaseGlucose Tolerance TestHumansHypoglycemic AgentsInsulinInsulin-Secreting CellsBenzeneacetamidesBlood GlucoseC-PeptideGlucokinaseHypoglycemic AgentsInsulinpiragliatin

Identifiers

PMID20739378
OpenAlexW2013481385

What OpenQuestion 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 OpenQuestion graph.