Evidence map›Paper›PMID 34120651›Full record

Trial reportBMC pharmacology & toxicology2021

Assessment of safety and tolerability of remogliflozin etabonate (GSK189075) when administered with total daily dose of 2000 mg of metformin.

Robert Dobbins, Elizabeth K Hussey, Robin O'Connor-Semmes, Susan Andrews, Wenli Tao, William O Wilkison, Bentley Cheatham, Katare Sagar, Barkate Hanmant

Registry-linked trialFull text readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BMC pharmacology & toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT00519480. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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.

NCT00519480 phase1completed

A Two-Week, Randomized, Double-Blind, Repeat-Dose, Parallel-Group Study to Evaluate the Safety and Tolerability of Metformin > 2000mg Co-Administered With Either GSK189075 500mg BID or GSK 189075 750mg BID to Subjects With Type 2 Diabetes Mellitus

Ran2007Enrolled50Registered outcomes5Posted comparisons0ConditionsDiabetes Mellitus, Type 2ArmsGSK189075, Metformin, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. 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.

Robert DobbinsIndivior, Inc., Durham, NC, USA.
Elizabeth K HusseyNuventra, Inc., Durham, NC, USA.
Robin O'Connor-SemmesParexel International, Durham, NC, USA.
Susan AndrewsGlaxoSmithKline, Collegeville, PA, USA.
Wenli TaoMetavant Sciences, Durham, NC, USA.
William O WilkisonAvolynt, Inc., RTP, 3920 South Alston Avenue, Durham, NC, 27713, USA.
Bentley CheathamAvolynt, Inc., RTP, 3920 South Alston Avenue, Durham, NC, 27713, USA. Bentley@avolynt.com.ORCID 0000-0001-9201-5602
Katare SagarGlenmark Pharmaceuticals Ltd, Mumbai, India.
Barkate HanmantGlenmark Pharmaceuticals Ltd, Mumbai, India.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPatients with type 2 diabetes mellitus (T2DM) are characterized by an elevated glycemic index and are at a higher risk for complications such as cardiovascular disease, nephropathy, retinopathy and peripheral neuropathy. Normalization of glycemic index can be achieved by dosing combinations of metformin with other anti-diabetic drugs. The present study (Clintrials number NCT00519480) was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of remogliflozinetabonate, an SGLT2 inhibitor, withdoses (500 mg and 750 mg BID) greater than the commercial dose (100 mg BID)in combination with metformin with minimum daily dose of 2000 mg given in two divided doses.

methodsThis was a randomized, double-blinded, repeat dose study in 50 subjects with T2DM. The study was conducted in three phases; run-in, randomization, and treatment. All subjects were on a stable metformin dosing regimen. Cohort 1 subjects were randomly allocated to receive either remogliflozin etabonate 500 mg BID or placebo BID (2:1) in addition to metformin. Cohort 2 subjects were administered with either remogliflozin etabonate 750 mg BID or placebo BID (2:1) in addition to metformin for 13 days. All the subjects were assessed for safety (adverse events, lactic acid levels, vital signs, electrocardiogram [ECG]), pharmacokinetic evaluation, and pharmacodynamics (Oral Glucose Tolerance Testing) parameters.

resultsCo-administration of remogliflozin etabonate and metformin was well tolerated in all subjects during the observation period. There were no severe or serious adverse events (SAEs) and no increase in lactic acid concentration was reported during the study. The statistical results showed that concomitant administration of remogliflozin etabonate, either 500 mg or 750 mg BID, with metformin had no effect on the pharmacokinetics of metformin. The accumulation ratios, Day 13 vs. Day 1, for AUC values of remogliflozin etabonate and its metabolites were all very close to 1, indicating no accumulation in plasma concentrations of remogliflozin etabonate and its metabolites. Mean glucose values from baseline and glucose and insulin values following oral glucose tolerance test (OGTT) were decreased in all treatment groups.

conclusionCo-administration of doses of remogliflozin etabonate (500 mg BID or 750 mg BID) greater than the commercial dose (100 mg BID) with metformin (2000 mg BID) was shown to be safe and effective during the observation period.

trial registrationClinicalTrials.gov , NCT00519480 . Registered:22 August 2007.

Indexed as

AdultBlood GlucoseBlood PressureDiabetes Mellitus, Type 2Double-Blind MethodDrug InteractionsDrug Therapy, CombinationFastingFemaleGlucosidesHumansHypoglycemic AgentsInsulinLactic AcidMaleMetforminBlood GlucoseGlucosidesHypoglycemic AgentsInsulinLactic AcidMetforminPyrazolesremogliflozin etabonateLactic acidosisMetforminPharmacodynamicsPharmacokineticsRemogliflozinRemogliflozin etabonateSafetySGLT2 inhibitorSodium-glucose transporters (SGLTs)Type 2 diabetes mellitus

Identifiers

PMID34120651
PMCPMC8201735

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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 OpenQuestion graph.