SynthesisEndocrinology, diabetes & metabolism2025

Efficacy and Safety of Pioglitazone Add-On in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin and Dapagliflozin: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Ubaid Khan, Zuhair Majeed, Muhammad Haris Khan, Ahmed Bostamy Elsnhory, Ahmed Mazen Amin, Anum Nawaz, Ahmed Raza, Hafiz Muhammad Waqas Siddque, Mustafa Turkmani, Mohamed Abuelazm

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in Endocrinology, diabetes & metabolism, 2025. The graph read 1 number from its abstract, feeding 1 cell of the map: it . Cited by 4 papers.

1number the graph read from it
1cell of the map it votes in
4citing 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.

← favours the treatmentfavours the comparator →
-0.540 · no effect
HbA1c levelspioglitazone add-on therapy vs metformin and dapagliflozinfavours the treatment · t2dfeeds one cell of the map
Δ -0.41-0.54 to -0.27< 0.00001
Pioglitazone add-on therapy significantly reduced HbA1c levels (MD: -0.41; 95% CI: -0.54 to -0.27, p = < 0.00001, I CONCLUSION: Pioglitazone add-on therapy significantly improved glycaemic control by reducing HbA1c, fasting blood glucose and HOMA-IR while increasing the likelihood of achieving HbA1c targets.

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 comparatorfavours the treatment →
0 · no effect
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

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. 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

10 authors.

Ubaid KhanDivision of Cardiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.ORCID https://orcid.org/0000-0003-3216-6323
Zuhair MajeedDepartment of Medicine, King Edward Medical University, Lahore, Pakistan.
Muhammad Haris KhanDepartment of Medicine, Saidu Medical College, Swat, Pakistan.ORCID https://orcid.org/0009-0000-3250-2601
Ahmed Bostamy ElsnhoryEmergency Medicine Department, Al-Bank Al-Ahly Hospital, Cairo, Egypt.
Ahmed Mazen AminFaculty of Medicine, Mansoura University, Mansoura, Egypt.
Anum NawazDepartment of Radiology, Pakistan Atomic Energy Commission Hospital, Islamabad, Pakistan.
Ahmed RazaDepartment of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan.ORCID https://orcid.org/0009-0004-1633-3827
Hafiz Muhammad Waqas SiddqueDepartment of Medicine, MedStar Health Georgetown University (Baltimore) Program, Baltimore, Maryland, USA.
Mustafa TurkmaniFaculty of Medicine, Michigan State University, East Lansing, Michigan, USA.ORCID https://orcid.org/0009-0001-4261-0638
Mohamed AbuelazmFaculty of Medicine, Tanta University, Tanta, Egypt.

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.

backgroundType 2 diabetes mellitus (T2DM) accounts for over 90% of diabetes cases worldwide. Pioglitazone, a thiazolidinedione, enhances insulin sensitivity by activating PPAR-γ. Evidence on its efficacy and safety as an add-on to metformin and SGLT2 inhibitors in inadequately controlled T2DM is limited. This systematic review and meta-analysis evaluates pioglitazone's role as a third-line therapy for improving glycaemic control in addition to metformin and Dapagliflozin. METHODOLOGY: We conducted comprehensive searches across PubMed, CENTRAL, WOS, Scopus and EMBASE until December 2024. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). This systematic review and meta-analysis is registered with PROSPERO ID: CRD42024612005.

resultsWe included three RCTs with 885 patients. Pioglitazone add-on therapy significantly reduced HbA1c levels (MD: -0.41; 95% CI: -0.54 to -0.27, p = < 0.00001, I

conclusionPioglitazone add-on therapy significantly improved glycaemic control by reducing HbA1c, fasting blood glucose and HOMA-IR while increasing the likelihood of achieving HbA1c targets. However, no significant difference was observed in HOMA-β between groups. These findings suggest the potential benefit of pioglitazone in enhancing glycaemic outcomes in diabetes management.

Indexed as

Benzhydryl CompoundsDiabetes Mellitus, Type 2GlucosidesHypoglycemic AgentsMetforminPioglitazoneBlood GlucoseDrug Therapy, CombinationGlycated HemoglobinHumansRandomized Controlled Trials as TopicSodium-Glucose Transporter 2 InhibitorsTreatment OutcomeBenzhydryl CompoundsBlood GlucosedapagliflozinGlucosidesGlycated HemoglobinHypoglycemic AgentsMetforminPioglitazoneSodium-Glucose Transporter 2 Inhibitorsdapagliflozinmetforminpioglitazonereviewtype 2 diabetes mellitus

Identifiers

PMID40420634
PMCPMC12106948

What Socratic holds

Texttitle and abstract
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.