SynthesisScientific reports2025

Efficacy and safety of GLP-1 agonists in the treatment of T2DM: A systematic review and network meta-analysis.

Xiaoyu Ren, Honghao Hua, Yuanqin Wu, Wei Zhang, Xianzhen Long, Yana Bai, Ning Cheng

Abstract readNetwork Meta-AnalysisSystematic Review
In one paragraph

Synthesis in Scientific reports, 2025. The graph read 9 numbers from its abstract, feeding 4 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 14 papers, 2 of them syntheses that pooled it.

9numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 2 pooled it
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.

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

HbA1-csemaglutide vs placebono interval or p-value · t2dfeeds one cell of the map
Δ -1.50
Compared to placebo, tirzepatide showed the greatest reduction in HbA1-c (MD: -2.3%) and FPG (MD: -3.1mmol/L); semaglutide was second (HbA1-c: MD: -1.5%; FPG: MD: -2mmol/L); liraglutide was third (HbA1-c: MD: -1.2% FPG: MD: -1.6mmol/L) (P<0.05).
HbA1-ctirzepatide vs placebono interval or p-value · t2dfeeds one cell of the map
Δ -2.30
Compared to placebo, tirzepatide showed the greatest reduction in HbA1-c (MD: -2.3%) and FPG (MD: -3.1mmol/L); semaglutide was second (HbA1-c: MD: -1.5%; FPG: MD: -2mmol/L); liraglutide was third (HbA1-c: MD: -1.2% FPG: MD: -1.6mmol/L) (P<0.05).
FPGtirzepatide vs placebono interval or p-value · t2dfeeds one cell of the map
Δ -3.10
Compared to placebo, tirzepatide showed the greatest reduction in HbA1-c (MD: -2.3%) and FPG (MD: -3.1mmol/L); semaglutide was second (HbA1-c: MD: -1.5%; FPG: MD: -2mmol/L); liraglutide was third (HbA1-c: MD: -1.2% FPG: MD: -1.6mmol/L) (P<0.05).
HbA1-cliraglutide vs placebono interval or p-value · t2dfeeds one cell of the map
Δ -1.20
Compared to placebo, tirzepatide showed the greatest reduction in HbA1-c (MD: -2.3%) and FPG (MD: -3.1mmol/L); semaglutide was second (HbA1-c: MD: -1.5%; FPG: MD: -2mmol/L); liraglutide was third (HbA1-c: MD: -1.2% FPG: MD: -1.6mmol/L) (P<0.05).
Body weightliraglutide vs placebono interval or p-value · t2dfeeds one cell of the map
Δ -1.20
Tirzepatide (MD: -9.1 kg), semaglutide (MD: -2.8 kg) and liraglutide (MD: -1.2 kg) (P<0.05) had significant reduction in body weight compared to placebo.
Body weightsemaglutide vs placebono interval or p-value · t2dfeeds one cell of the map
Δ -2.80
Tirzepatide (MD: -9.1 kg), semaglutide (MD: -2.8 kg) and liraglutide (MD: -1.2 kg) (P<0.05) had significant reduction in body weight compared to placebo.
Body weighttirzepatide vs placebono interval or p-value · t2dfeeds one cell of the map
Δ -9.10
Tirzepatide (MD: -9.1 kg), semaglutide (MD: -2.8 kg) and liraglutide (MD: -1.2 kg) (P<0.05) had significant reduction in body weight compared to placebo.
FPGliraglutide vs placebono interval or p-value · t2dfeeds one cell of the map
Δ -1.60
Compared to placebo, tirzepatide showed the greatest reduction in HbA1-c (MD: -2.3%) and FPG (MD: -3.1mmol/L); semaglutide was second (HbA1-c: MD: -1.5%; FPG: MD: -2mmol/L); liraglutide was third (HbA1-c: MD: -1.2% FPG: MD: -1.6mmol/L) (P<0.05).
FPGsemaglutide vs placebono interval or p-value · t2dfeeds one cell of the map
Δ -2.00
Compared to placebo, tirzepatide showed the greatest reduction in HbA1-c (MD: -2.3%) and FPG (MD: -3.1mmol/L); semaglutide was second (HbA1-c: MD: -1.5%; FPG: MD: -2mmol/L); liraglutide was third (HbA1-c: MD: -1.2% FPG: MD: -1.6mmol/L) (P<0.05).

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.

GIP/GLP-1 & amylin agonists×glycemic control

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

24 readable studies in this cell: 21 favour the treatment, 3 find no difference, 0 favour the comparator.

Belief with this paper
0.88established · 15 families support, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT041846222,539 enrolled · 2019
Δ -0.33-0.36 to -0.30
NCT037306622,002 enrolled · 2018
Δ -0.99-1.13 to -0.86
NCT039879191,879 enrolled · 2019
Δ -0.51-0.64 to -0.38
NCT038829701,444 enrolled · 2019
Δ -0.86-1.00 to -0.72
NCT045379231,428 enrolled · 2020
Δ -1.10-1.24 to -0.97
NCT04093752917 enrolled · 2019
Δ -1.49-1.69 to -1.29
NCT04660643783 enrolled · 2021
Δ -8.92-10.4 to -7.43
NCT03861052636 enrolled · 2019
Δ -1.09-1.27 to -0.90
NCT04657016579 enrolled · 2021
Δ -11.2-13.5 to -8.80
NCT03954834478 enrolled · 2019
Δ -1.91-2.18 to -1.63
NCT04039503475 enrolled · 2019
Δ -1.66-1.88 to -1.43
NCT03131687318 enrolled · 2017
Δ -0.80-1.20 to -0.40

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

GIP/GLP-1 & amylin agonists×body weight & composition

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

29 readable studies in this cell: 28 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
1.00replicated · 19 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
Δ -17.3-18.1 to -16.6
NCT041846222,539 enrolled · 2019
Δ -13.5-14.6 to -12.5
NCT037306622,002 enrolled · 2018
Δ -9.00-9.80 to -8.30
NCT039879191,879 enrolled · 2019
Δ -1.70-2.60 to -0.70
NCT038829701,444 enrolled · 2019
Δ -9.80-10.8 to -8.80
NCT045379231,428 enrolled · 2020
Δ -10.7-11.5 to -9.90
Δ -10.4-11.2 to -9.50
NCT04657003938 enrolled · 2021
Δ -10.1-11.5 to -8.80
NCT04093752917 enrolled · 2019
Δ -6.50-7.40 to -5.60
NCT04660643783 enrolled · 2021
Δ -21.4-22.9 to -20.0
NCT05822830751 enrolled · 2023
Δ -6.50-8.10 to -4.90
NCT04847557731 enrolled · 2021
Δ -11.6-12.8 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.

GLP-1 receptor agonists×glycemic control

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

40 readable studies in this cell: 96 favour the treatment, 17 find no difference, 10 favour the comparator.

Belief with this paper
0.91replicated · 68 families support, 7 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017204463,297 enrolled · 2013
Δ -0.66-0.80 to -0.52
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT039879191,879 enrolled · 2019
Δ -0.51-0.64 to -0.38
NCT026078651,864 enrolled · 2016
Δ -0.50-0.60 to -0.40
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT040178321,441 enrolled · 2019
Δ -0.20-0.30 to -0.10
NCT018365231,398 enrolled · 2013
Δ -0.20-0.32 to -0.07
NCT019301881,231 enrolled · 2013
Δ -1.06-1.21 to -0.91
NCT007344741,202 enrolled · 2008
Δ -0.71-0.87 to -0.55
NCT020581471,170 enrolled · 2014
Δ -0.29-0.38 to -0.19
NCT003184611,091 enrolled · 2006
Δ -1.09-1.30 to -0.88
NCT021289321,089 enrolled · 2014
Δ -0.81-0.96 to -0.67

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

GLP-1 receptor agonists×body weight & composition

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

40 readable studies in this cell: 83 favour the treatment, 15 find no difference, 11 favour the comparator.

Belief with this paper
0.90replicated · 64 families support, 7 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT012722193,731 enrolled · 2011
Δ -5.39-5.82 to -4.95
Δ -17.3-18.1 to -16.6
NCT017204463,297 enrolled · 2013
Δ -2.95-3.47 to -2.44
NCT035489351,961 enrolled · 2018
Δ -12.4-13.4 to -11.5
NCT039879191,879 enrolled · 2019
Δ -1.70-2.60 to -0.70
NCT026078651,864 enrolled · 2016
Δ -2.50-3.00 to -2.00
NCT056467061,407 enrolled · 2023
Δ -14.8-16.2 to -13.4
NCT018365231,398 enrolled · 2013
Δ -4.90-5.65 to -4.16
NCT035527571,210 enrolled · 2018
Δ -6.21-7.28 to -5.15
NCT007344741,202 enrolled · 2008
Δ -1.50-2.08 to -0.92
Δ -10.4-11.2 to -9.50
NCT020581471,170 enrolled · 2014
Δ 14.38.37 to 20.3

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

14 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. 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

7 authors.

Xiaoyu RenKey Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, 730000, Gansu, P.R. China.
Honghao HuaInstitute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China.
Yuanqin WuInstitute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China.
Wei ZhangKey Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, 730000, Gansu, P.R. China.
Xianzhen LongInstitute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China.
Yana BaiInstitute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China.
Ning ChengKey Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, 730000, Gansu, P.R. China. 1184231755@qq.com.

Funding

National Natural Science Foundation of China (NO. 81673248
8 · The paper itself

Abstract

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

To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in subjects with type 2 diabetes (T2DM). Electronic databases were searched from inception to 2nd October 2024 for randomised controlled trials comparing GLP-1RAs treating T2DM. Bayesian network meta-analyses were conducted to analyze metabolic and safety outcomes. 64 trials comprising of 25,572 participants were identified. Compared to placebo, tirzepatide showed the greatest reduction in HbA1-c (MD: -2.3%) and FPG (MD: -3.1mmol/L); semaglutide was second (HbA1-c: MD: -1.5%; FPG: MD: -2mmol/L); liraglutide was third (HbA1-c: MD: -1.2% FPG: MD: -1.6mmol/L) (P<0.05). All treatments showed no statistically significant differences in BMI, SBP, DBP, TC, HDL-C and LDL-C compared to placebo. Tirzepatide (MD: -9.1 kg), semaglutide (MD: -2.8 kg) and liraglutide (MD: -1.2 kg) (P<0.05) had significant reduction in body weight compared to placebo. GLP-1 RAs had higher risk of gastrointestinal symptoms. Semaglutide increased the risk of hypoglycemia compared to placebo while liraglutide reduced the risk of hypoglycemia compared to traditional antidiabetic drugs. GLP-1RAs improve glycaemic control, with tirzepatide, semaglutide and liraglutide exhibiting the most significant improvements. Tirzepatide is more suitable for treating T2DM with obesity. For individuals with normal weight, both semaglutide and liraglutide are generally more effective for treating T2DM. However, considering the potential for semaglutide to cause hypoglycemia, liraglutide may be the optimal choice for T2DM treatment to minimize the risk of hypoglycemia.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsBlood GlucoseGlucagon-Like Peptide 1Glucagon-Like PeptidesGlycated HemoglobinHumansLiraglutideRandomized Controlled Trials as TopicSemaglutideTirzepatideTreatment OutcomeBlood GlucoseGlucagon-Like Peptide 1Glucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like PeptidesGlycated HemoglobinHypoglycemic AgentsLiraglutideSemaglutideTirzepatideGlucagon-like peptide-1 receptor agonistsNetwork meta-analysisType 2 diabetes mellitus

Identifiers

PMID40619508
PMCPMC12230154

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
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.