Trial reportJournal of internal medicine2009

Free fatty acid kinetics during long-term treatment with pioglitazone added to sulfonylurea or metformin in Type 2 diabetes.

M Roden, S Mariz, A R Brazzale, G Pacini

Open access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Journal of internal medicine, 2009. The graph read 2 numbers from its abstract, feeding 1 cell of the map: it . Cited by 6 papers, 2 of them syntheses that pooled it.

2numbers the graph read from it
1cell of the map it votes in
6citing papers in PubMed, 2 pooled it
0.9field-weighted citation impact, top 24% 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 →
-0.110 · no effect
Fasting FFAspioglitazone vs metformin, in added to metforminfavours the treatment · t2dfeeds one cell of the map
Δ -0.11P<0.05
RESULTS: At Week 104, pioglitazone treatment decreased fasting FFAs by 0.08 mmol L(-1) when added to sulfonylurea and by 0.11 mmol L(-1) when added to metformin versus the respective sulfonylurea + metformin groups (0.03 mmol L(-1), P=0.05 and 0.04 mmol L(-1), P<0.05), and this was accompanied by significant improvements in fasting adipose tissue insulin sensitivity.
Fasting FFAspioglitazone vs metformin, in added to sulfonylureano clear difference · t2dfeeds one cell of the map
Δ -0.08P=0.05
RESULTS: At Week 104, pioglitazone treatment decreased fasting FFAs by 0.08 mmol L(-1) when added to sulfonylurea and by 0.11 mmol L(-1) when added to metformin versus the respective sulfonylurea + metformin groups (0.03 mmol L(-1), P=0.05 and 0.04 mmol L(-1), P<0.05), and this was accompanied by significant improvements in fasting adipose tissue insulin sensitivity.

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.

Thiazolidinediones×glycemic control

No readable resultOpen on the map →What to test next →

16 readable studies in this cell: 9 favour the treatment, 4 find no difference, 3 favour the comparator.

Belief with this paper
0.83established · 5 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2009
Δ -0.11
NCT00676338820 enrolled · 2008
Δ 0.10-0.15 to 0.35
NCT00839527685 enrolled · 2009
Δ 0.250.10 to 0.40
NCT00727857600 enrolled · 2007
Δ 0.840.50 to 1.18
NCT01076075427 enrolled · 2010
Δ -0.68-0.87 to -0.50
NCT00770653305 enrolled · 2007
Δ 0.16-0.02 to 0.33
NCT0158944577 enrolled · 2008
Δ -0.74-7.90 to 8.00
NCT0031865623 enrolled · 2005
Δ 5.02-0.32 to 10.4
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

6 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.The Cochrane database of systematic reviews · 2010 · on this map
    Pooled it
  3. MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025
    Review
  4. Review
  5. Article
  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

4 authors at 3 institutions in 4 countries.

M RodenDepartment of Medicine/Metabolic Diseases, Institute for Clinical Diabetology, German Diabetes Center, Heinrich Heine University, Düsseldorf, Germany. michael.roden@ddz.uni-duesseldorf.de
S Mariz
A R Brazzale
G Pacini
Institute for Biomedical Research and Innovation · ITKarl Landsteiner Society · ATTakeda (United Kingdom) · GB

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.

backgroundFree fatty acids (FFAs) are linked to impaired insulin action, but their role in mediating long-term insulin sensitization during diabetes treatment is unclear.

objectivesTo examine the effect of pioglitazone addition to existing therapy on FFA dynamics and insulin action.

designTwo 2-year, randomized, parallel-group, double-blind, double-dummy, clinical trials.

settingOne hundred and seventy-one centres in Europe, Australia and Canada. SUBJECTS: Male and female patients with Type 2 diabetes inadequately managed with metformin or sulfonylurea.

interventionsPatients were randomized to pioglitazone (15-45 mg day(-1); n=319) or metformin (850-2550 mg day(-1); n=320) as add-on therapy to gliclazide or pioglitazone (n=317) versus gliclazide (80-320 mg day(-1); n=313) as add-on therapy to metformin. OUTCOME MEASURE: Plasma FFA profiles during oral glucose tolerance tests in selected centres before and during treatment (n=588).

resultsAt Week 104, pioglitazone treatment decreased fasting FFAs by 0.08 mmol L(-1) when added to sulfonylurea and by 0.11 mmol L(-1) when added to metformin versus the respective sulfonylurea + metformin groups (0.03 mmol L(-1), P=0.05 and 0.04 mmol L(-1), P<0.05), and this was accompanied by significant improvements in fasting adipose tissue insulin sensitivity. Changes in postchallenge FFAs were similar between groups and not related to changes in liver transaminases, insulin action and secretion. However, the sensitivity of FFA to insulin was affected by treatment (P<0.001) and visit (P<0.05). Insulin sensitivity of FFA rose when pioglitazone was added to sulfonylurea (P<0.05), but decreased for gliclazide + metformin (P<0.05).

conclusionLong-term improvements in adipose tissue insulin sensitivity and reduction in fasting FFAs with pioglitazone may help to reduce lipotoxicity in Type 2 diabetes.

Indexed as

AdultAgedAnalysis of VarianceBlood GlucoseDiabetes Mellitus, Type 2Double-Blind MethodFatty Acids, NonesterifiedFemaleGliclazideGlucose Tolerance TestGlycated HemoglobinHumansHypoglycemic AgentsMaleMetforminMiddle AgedBlood GlucoseFatty Acids, NonesterifiedGliclazideGlycated HemoglobinHypoglycemic AgentsMetforminPioglitazoneSulfonylurea CompoundsThiazolidinediones

Identifiers

PMID19298459
OpenAlexW2017179973

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

None linked

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.