Evidence mapPaperPMID 23668634Full record

Trial reportBMC pharmacology & toxicology2013

First human dose-escalation study with remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2 (SGLT2), in healthy subjects and in subjects with type 2 diabetes mellitus.

Anita Kapur, Robin O'Connor-Semmes, Elizabeth K Hussey, Robert L Dobbins, Wenli Tao, Marcus Hompesch, Glenn A Smith, Joseph W Polli, Charles D James, Imao Mikoshiba and 1 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in BMC pharmacology & toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01571661 (A Double Blind, Randomized, Placebo Controlled, Single-dose Escalation, First-time-in-human Crossover Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of GSK189075A in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus), which is not on this map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.1field-weighted citation impact, top 8% 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.

NCT01571661 phase1completednot on this map

A Double Blind, Randomized, Placebo Controlled, Single-dose Escalation, First-time-in-human Crossover Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of GSK189075A in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus

TypeinterventionalSponsorGlaxoSmithKlineRan2004 to 2005Enrolled16ConditionsDiabetes Mellitus, Type 2ArmsGSK189075A, Placebo
3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 51 citations in OpenAlex.

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  19. Clinical implications of canagliflozin treatment in patients with type 2 diabetes.Clinical diabetes : a publication of the American Diabetes Association · 2015
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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

11 authors at 5 institutions in 3 countries.

Anita Kapur
Robin O'Connor-Semmes
Elizabeth K Hussey
Robert L Dobbins
Wenli Tao
Marcus Hompesch
Glenn A Smith
Joseph W Polli
Charles D James
Imao Mikoshiba
Derek J Nunez
Research Triangle Park Foundation · USGlaxoSmithKline (United States) · USDurham University · GBKissei Pharmaceutical (Japan) · JPProfil Institute for Clinical Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRemogliflozin etabonate (RE) is the prodrug of remogliflozin, a selective inhibitor of the renal sodium-dependent glucose transporter 2 (SGLT2), which could increase urine glucose excretion (UGE) and lower plasma glucose in humans.

methodsThis double-blind, randomized, placebo-controlled, single-dose, dose-escalation, crossover study is the first human trial designed to evaluate safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of RE. All subjects received single oral doses of either RE or placebo separated by approximately 2 week intervals. In Part A, 10 healthy subjects participated in 5 dosing periods where they received RE (20 mg, 50 mg, 150 mg, 500 mg, or 1000 mg) or placebo (4:1 active to placebo ratio per treatment period). In Part B, 6 subjects with type 2 diabetes mellitus (T2DM) participated in 3 dose periods where they received RE (50 mg and 500 mg) or placebo (2:1 active to placebo per treatment period). The study protocol was registered with the NIH clinical trials data base with identifier NCT01571661.

resultsRE was generally well-tolerated; there were no serious adverse events. In both populations, RE was rapidly absorbed and converted to remogliflozin (time to maximum plasma concentration [Cmax;Tmax] approximately 1 h). Generally, exposure to remogliflozin was proportional to the administered dose. RE was rapidly eliminated (mean T½ of ~25 min; mean plasma T½ for remogliflozin was 120 min) and was independent of dose. All subjects showed dose-dependent increases in 24-hour UGE, which plateaued at approximately 200 to 250 mmol glucose with RE doses ≥150 mg. In T2DM subjects, increased plasma glucose following OGTT was attenuated by RE in a drug-dependent fashion, but there were no clear trends in plasma insulin. There were no apparent effects of treatment on plasma or urine electrolytes.

conclusionsThe results support progression of RE as a potential treatment for T2DM.

trial registrationClinicalTrials.gov NCT01571661.

Indexed as

Sodium-Glucose Transporter 2 InhibitorsAdultArea Under CurveBlood GlucoseCross-Over StudiesDiabetes Mellitus, Type 2DiarrheaDizzinessDose-Response Relationship, DrugDouble-Blind MethodElectrolytesFemaleGlucosidesHeadacheHumansHypoglycemic AgentsBlood GlucoseElectrolytesGlucosidesHypoglycemic AgentsInsulinPyrazolesremogliflozin etabonateSLC5A2 protein, humanSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID23668634
PMCPMC3700763
OpenAlexW2097418545

What Socratic holds

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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.