Evidence map›Paper›PMID 34006325›Full record

ReviewCardiovascular diabetology2021

Rethinking pioglitazone as a cardioprotective agent: a new perspective on an overlooked drug.

Lorenzo Nesti, Domenico Tricò, Alessandro Mengozzi, Andrea Natali

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Cardiovascular diabetology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
12.7field-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.

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

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.

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  11. Fluid retention versus cardio protection: rethinking pioglitazone.Annals of medicine and surgery (2012) · 2026
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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

4 authors at 2 institutions in 1 country.

Lorenzo NestiMetabolism, Nutrition, and Atherosclerosis Laboratory, Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy. lorenzo.nesti@phd.unipi.it.ORCID 0000-0002-0560-6496
Domenico TricòMetabolism, Nutrition, and Atherosclerosis Laboratory, Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
Alessandro MengozziInstitute of Life Sciences, Sant'Anna School of Advanced Studies, Pisa, Italy.
Andrea NataliMetabolism, Nutrition, and Atherosclerosis Laboratory, Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
University of Pisa · ITScuola Superiore Sant'Anna · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Since 1985, the thiazolidinedione pioglitazone has been widely used as an insulin sensitizer drug for type 2 diabetes mellitus (T2DM). Although fluid retention was early recognized as a safety concern, data from clinical trials have not provided conclusive evidence for a benefit or a harm on cardiac function, leaving the question unanswered. We reviewed the available evidence encompassing both in vitro and in vivo studies in tissues, isolated organs, animals and humans, including the evidence generated by major clinical trials. Despite the increased risk of hospitalization for heart failure due to fluid retention, pioglitazone is consistently associated with reduced risk of myocardial infarction and ischemic stroke both in primary and secondary prevention, without any proven direct harm on the myocardium. Moreover, it reduces atherosclerosis progression, in-stent restenosis after coronary stent implantation, progression rate from persistent to permanent atrial fibrillation, and reablation rate in diabetic patients with paroxysmal atrial fibrillation after catheter ablation. In fact, human and animal studies consistently report direct beneficial effects on cardiomyocytes electrophysiology, energetic metabolism, ischemia-reperfusion injury, cardiac remodeling, neurohormonal activation, pulmonary circulation and biventricular systo-diastolic functions. The mechanisms involved may rely either on anti-remodeling properties (endothelium protective, inflammation-modulating, anti-proliferative and anti-fibrotic properties) and/or on metabolic (adipose tissue metabolism, increased HDL cholesterol) and neurohormonal (renin-angiotensin-aldosterone system, sympathetic nervous system, and adiponectin) modulation of the cardiovascular system. With appropriate prescription and titration, pioglitazone remains a useful tool in the arsenal of the clinical diabetologist.

Indexed as

AnimalsCardiovascular DiseasesCardiovascular SystemDiabetes Mellitus, Type 2HumansHypoglycemic AgentsPioglitazonePPAR gammaRisk AssessmentRisk FactorsSignal TransductionTreatment OutcomeHypoglycemic AgentsPioglitazonePPAR gammaPPARG protein, humanCardioprotectionCardiovascularCardiovascular preventionCardiovascular risk factorsClinical managementHeart failurePharmacologic effectsPioglitazonePPARsType 2 diabetes

Identifiers

PMID34006325
PMCPMC8130304
OpenAlexW3162939481

What Socratic holds

Textmetadata
LicenceCC BY
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.