SynthesisScientific reports2024

PPAR agonists as add-on treatment with metformin in management of type 2 diabetes: a systematic review and meta-analysis.

Saif Alnuaimi, Tea Reljic, Fatima S Abdulla, Hamda Memon, Sarah Al-Ali, Teagen Smith, Fadila Serdarevic, Zelija Velija Asimi, Ambuj Kumar, Sabina Semiz

Open access · goldAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Scientific reports, 2024. The graph read 4 numbers from its abstract, feeding 1 cell of the map: it . Cited by 12 papers.

4numbers the graph read from it
1cell of the map it votes in
12citing papers in PubMed
4.9field-weighted citation impact, top 4% 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 →
-27.20 · no effect
HOMA-IRPPAR agonist plus metformin vs metformin alonefavours the treatment · t2dfeeds one cell of the map
Δ -1.26-2.16 to -0.37
Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events.
HbA1cPPAR agonist plus metformin vs metformin alonefavours the treatment · t2dfeeds one cell of the map
Δ -0.53-0.67 to -0.38
Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events.
Fasting glucosePPAR agonist plus metformin vs metformin alonefavours the treatment · t2dfeeds one cell of the map
Δ -22.1-27.2 to -17.0
Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events.

Read, but not usablea number the graph found but could not read as for or against

Fasting insulinPPAR agonist plus metformin vs metformin alonedirection of benefit for this outcome is not defined · t2dfeeds one cell of the map
Δ -19.8-29.5 to -10.1
Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events.

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×glycemic control

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

40 readable studies in this cell: 41 favour the treatment, 12 find no difference, 8 favour the comparator.

Belief with this paper
0.84replicated · 32 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017190031,413 enrolled · 2012
Adjusted mean -0.72-0.95 to -0.48
NCT018093271,186 enrolled · 2013
Δ -0.40-0.59 to -0.21
NCT022730501,136 enrolled · 2014
Δ -0.89-1.08 to -0.69
NCT008598981,093 enrolled · 2009
Δ -0.53-0.74 to -0.32
Δ -0.85-43.8 to 26.7
NCT00643851994 enrolled · 2008
Δ -0.86-1.11 to -0.62
NCT01708902876 enrolled · 2012
Δ -1.00-1.23 to -0.78
NCT00676338820 enrolled · 2008
Δ -0.05-0.26 to 0.17
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT01076088744 enrolled · 2010
Δ -0.84-1.15 to -0.52
NCT00386100688 enrolled · 2006
Δ -0.49-0.67 to -0.30

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

12 citing papers in PubMed, 21 citations in OpenAlex.

  1. Trial
  2. Article
  3. Novel Small Molecule GLP-1R Agonists Based on 1Molecules (Basel, Switzerland) · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Molecular Mechanisms of Cadmium-Induced Toxicity and Its Modification.International journal of molecular sciences · 2025
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
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 at 3 institutions in 4 countries.

Saif AlnuaimiCollege of Medicine and Health Sciences, Khalifa University, PO Box 127788, Abu Dhabi, United Arab Emirates.
Tea ReljicResearch Methodology and Biostatistics Core, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Fatima S AbdullaCollege of Medicine and Health Sciences, Khalifa University, PO Box 127788, Abu Dhabi, United Arab Emirates.
Hamda MemonCollege of Medicine and Health Sciences, Khalifa University, PO Box 127788, Abu Dhabi, United Arab Emirates.
Sarah Al-AliCollege of Medicine and Health Sciences, Khalifa University, PO Box 127788, Abu Dhabi, United Arab Emirates.
Teagen SmithResearch Methodology and Biostatistics Core, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Fadila SerdarevicSarajevo Medical School, University Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina.
Zelija Velija AsimiSarajevo Medical School, University Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina.
Ambuj KumarResearch Methodology and Biostatistics Core, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Sabina SemizCollege of Medicine and Health Sciences, Khalifa University, PO Box 127788, Abu Dhabi, United Arab Emirates. sabina.semiz@ku.ac.ae.ORCID 0000-0003-2629-4660
Khalifa University of Science and Technology · AEUniversity of South Florida · USSarajevo School of Science and Technology · BA

Funding

Khalifa University 8474000253/FSU-2020-29/2020
8 · The paper itself

Abstract

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

The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.

Indexed as

Diabetes Mellitus, Type 2Drug Therapy, CombinationHypoglycemic AgentsMetforminPeroxisome Proliferator-Activated ReceptorsBlood GlucoseGlycated HemoglobinHumansRandomized Controlled Trials as TopicBlood GlucoseGlycated HemoglobinHypoglycemic AgentsMetforminPeroxisome Proliferator-Activated ReceptorsGastrointestinal intoleranceGlycemic controlInsulin resistanceLipidsSafety profile

Identifiers

PMID38627464
PMCPMC11021491
OpenAlexW4394856932

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.