Trial reportJournal of clinical lipidology

Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus.

Ronald B Goldberg, Robert S Rosenson, Eric Hernandez-Triana, Soamnauth Misir, Michael R Jones

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Journal of clinical lipidology. The graph read 1 number from its abstract, feeding 3 cells of the map: it finds no clear difference in 3. It reports registered trial NCT00570739. Cited by 6 papers, 1 of them a synthesis that pooled it.

1number the graph read from it
3cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 23% 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.

← favours the treatmentfavours the comparator →
8.300 · no effect
Lipidsno clear difference · against placebo · dyslipidemia, t2dfeeds 3 cells of the map
change 8.30P = .06
Metformin plus colesevelam significantly reduced total LDL-P (mean treatment difference: absolute change -186 nmol/L [percent change -11.7%]; both P < .0001), largely attributable to a reduction in small LDL-P, and increased total very-low-density lipoprotein particle concentration (mean treatment difference: absolute change 6 nmol/L; P = .03 [percent change 8.3%; P = .06]) and total high-density lipoprotein particle concentration (1.0 μmol/L; P = .03 [4.5%; P = .01]) versus metformin plus placebo.

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Metformin×lipids

InconclusiveOpen on the map →What to test next →

10 readable studies in this cell: 4 favour the treatment, 5 find no difference, 1 favour the comparator.

Belief with this paper
0.50contested · 3 families support, 1 contradict · against placebo
Without it
0.50This paper does not move the number.
← favours the comparatorfavours the treatment →
0 · no effect
This paper502 enrolled · 2007
change 8.30
NCT00676338820 enrolled · 2008
Δ -0.01-0.18 to 0.15
NCT00386100688 enrolled · 2006
Δ -11.3-20.6 to -0.90
NCT00727857600 enrolled · 2007
Δ 23.4-44.6 to 91.4
NCT00868790118 enrolled · 2009
Δ -3.90-10.2 to 2.30
NCT0158944577 enrolled · 2008
Δ -9.06-88.0 to 118

Other glucose-lowering×lipids

InconclusiveOpen on the map →What to test next →

3 readable studies in this cell: 0 favour the treatment, 2 find no difference, 1 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 1 contradict · against placebo
Without it
0.00This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper502 enrolled · 2007
change 8.30

Other lipid agents×lipids

InconclusiveOpen on the map →What to test next →

28 readable studies in this cell: 17 favour the treatment, 2 find no difference, 9 favour the comparator.

Belief with this paper
0.50contested · 17 families support, 6 contradict · against placebo
Without it
0.50This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper502 enrolled · 2007
change 8.30
NCT004793881,216 enrolled · 2007
Δ -4.50-7.70 to -1.30
NCT00862251808 enrolled · 2009
Percent change in least-square means -14.8-19.6 to -9.91
NCT00485758796 enrolled · 2007
Δ -17.9-21.4 to -14.4
NCT00730132712 enrolled · 2008
Δ -5.75-9.43 to -2.07
NCT01763827615 enrolled · 2013
Δ -39.3-43.3 to -35.3
NCT01984424511 enrolled · 2013
Δ -37.8-42.3 to -33.3
NCT06005597407 enrolled · 2024
Least Squares (LS) Means -27.9-37.5 to -18.4
NCT03337308382 enrolled · 2017
Δ -38.0-46.5 to -29.6
NCT02227784366 enrolled · 2014
Δ -6.14-12.2 to -0.22
NCT01763905307 enrolled · 2013
Δ -38.1-43.7 to -33.0
NCT03001076269 enrolled · 2016
Δ -28.4-34.4 to -22.5
4 · 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.

NCT00570739 phase3completed

Effects of Metformin HCl in Combination With Colesevelam HCl, Compared to Metformin HCl Alone, as Initial Therapy in Drug naïve Subjects With Type 2 Diabetes Mellitus, and the Effects of Colesevelam HCl on the Lipid Profile in Subjects With Pre Diabetes

Ran2007Enrolled502Registered outcomes66Posted comparisons270ConditionsHypercholesterolemia, Pre-diabetes, Type 2 Diabetes MellitusArmsColesevelam, Colesevelam placebo, Metformin HCl and Colesevelam Placebo, Metformin HCl tablets and Colesevelam tablets
Open the trial in the graph
5 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Review
  6. Article
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

5 authors at 4 institutions in 2 countries.

Ronald B GoldbergDivision of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine, Miami, FL 33136, USA. rgoldber@med.miami.edu
Robert S Rosenson
Eric Hernandez-Triana
Soamnauth Misir
Michael R Jones
Daiichi Sankyo (United States) · USIcahn School of Medicine at Mount Sinai · USUniversidad del Rosario · COUniversity of Miami · US

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundThe bile acid sequestrant colesevelam has been shown to significantly reduce low-density lipoprotein particle concentration (LDL-P) in adults with primary hyperlipidemia or type 2 diabetes mellitus (T2DM).

objectiveTo assess the effect of initial combination therapy with metformin plus colesevelam on lipoprotein particles in patients with T2DM (secondary efficacy variables).

methodsThis 16-week, randomized, double-blind, placebo-controlled study enrolled drug-naïve adults with T2DM, glycated hemoglobin 6.5%-10.0%, low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL, and triglycerides <500 mg/dL. Patients were randomized 1:1 to either open-label metformin (titrated to 1700 mg/day) plus double-blind colesevelam 3.75 g/day or open-label metformin plus double-blind placebo.

resultsIn total, 286 patients were randomized (metformin plus colesevelam [n = 145]; metformin plus placebo [n = 141]). Compared with metformin plus placebo, the combination of metformin plus colesevelam significantly reduced LDL-C (mean treatment difference: -16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), and apolipoprotein (apo) B (-8.0%) and significantly increased triglycerides (median treatment difference: 18.6%) and apoA-I (mean treatment difference: 4.4%; all P < .001). Metformin plus colesevelam significantly reduced total LDL-P (mean treatment difference: absolute change -186 nmol/L [percent change -11.7%]; both P < .0001), largely attributable to a reduction in small LDL-P, and increased total very-low-density lipoprotein particle concentration (mean treatment difference: absolute change 6 nmol/L; P = .03 [percent change 8.3%; P = .06]) and total high-density lipoprotein particle concentration (1.0 μmol/L; P = .03 [4.5%; P = .01]) versus metformin plus placebo.

conclusionInitial combination therapy with metformin plus colesevelam improved the atherogenic lipoprotein profile of patients with early T2DM by significantly reducing LDL-P. ClinicalTrials.gov identifier: NCT00570739.

Indexed as

AdultAllylamineAnticholesteremic AgentsApolipoprotein A-IApolipoproteins BCholesterol, HDLCholesterol, LDLColesevelam HydrochlorideDiabetes Mellitus, Type 2Double-Blind MethodDrug Administration ScheduleDrug Therapy, CombinationFemaleGlycated HemoglobinHumansHyperlipidemiasAllylamineAnticholesteremic AgentsApolipoprotein A-IApolipoproteins BCholesterol, HDLCholesterol, LDLColesevelam HydrochlorideGlycated HemoglobinLipoproteins, LDLMetforminTriglycerides

Identifiers

PMID22836068
OpenAlexW2002646514

What Socratic holds

Texttitle and abstract
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 Socratic graph.