Comparing the effectiveness of long-term use of daily and weekly glucagon-like peptide-1 receptor agonists treatments in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus: a network meta-analysis.

Yuan X, Gao Z, Yang C, Duan K, Ren L, Song G

Frontiers in endocrinology5 Jun 2023Cited by 14 (Europe PMC)

PMID37342259PMCIDPMC10277636DOI10.3389/fendo.2023.1170881PepBankPUB-37342259

Summary

ObjectiveIn the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).MethodWe used Stata 17.0 for the NMA. Eligible Randomized controlled trials (RCTs) were searched in PubMed, Cochrane, and Embase databases until December 2022. Two researchers independently screened the available studies. The Cochrane Risk of Bias tool was used to assess the risk of bias in the included studies. We used GRADEprofiler (version3.6) to analyze the evidence certainty. Primary outcomes such as liver fat content (LFC), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels, as well as secondary outcomes such as γ-glutamyltransferase (γGGT) and body weight, were evaluated. Then, each intervention was ranked by the surface under the cumulative ranking curve (SUCRA). As a supplement, we drew forest plots of subgroup using RevMan (version 5.4).ResultsFourteen RCTs involving 1666 participants were included in the present study. The NMA results showed that exenatide (bid) was the best treatment for improving LFC compared with other agents, liraglutide, dulaglutide, semaglutide (qw) and placebo), and the SUCRA values were 66.8%. Among five interventions (except exenatide (bid) and semaglutide (qw)) evaluated for AST outcome, and six interventions (except exenatide (bid)) evaluated for ALT outcome, semaglutide (qd) was the most effective drug (SUCRA (AST) = 100%, SUCRA (ALT) = 95.6%). The result of LFC in daily group was MD = -3.66, 95% CI [-5.56, -1.76] and in weekly GLP-1RAs group, it was MD = -3.51, 95% CI [-4, -3.02]. As to AST and ALT, the results in daily group versus weekly group were AST: MD = -7.45, 95% CI [-14.57, -0.32] versus MD= -0.58, 95% CI [-3.18, 2.01] and ALT: MD = -11.12, 95% CI [-24.18, 1.95] versus MD = -5.62, 95% CI [-15.25, 4]. The quality of evidence was assessed as moderate or low.ConclusionThe daily GLP-1RAs may be more effective in primary outcomes. And the daily semaglutide may be the most effective treatment for NAFLD and T2DM among the six interventions.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study11

2 results from studies that gave the peptide. 2 results from people.

01HumanSystematic reviewEfficacy outcome
In a network meta-analysis in adults with NAFLD and T2DM, daily semaglutide ranked as the most effective drug for AST (SUCRA 100%).
In plain wordsIn a network meta-analysis of adults with fatty liver and type 2 diabetes, daily semaglutide ranked best for lowering the liver enzyme AST.
Peptide
Semaglutide
Outcome
DecreaseAST (SUCRA ranking)
Study
n: not reported in source
Comparator
Other interventions in the network
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Measurements
SUCRA
100%
AST
Source sentences
Summary
Among five interventions (except exenatide (bid) and semaglutide (qw)) evaluated for AST outcome, and six interventions (except exenatide (bid)) evaluated for ALT outcome, semaglutide (qd) was the most effective drug (SUCRA (AST) = 100%, SUCRA (ALT) = 95.6%).
2 context sentences(design, population, supporting numbers)
Summary · context
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).
Summary · context
Fourteen RCTs involving 1666 participants were included in the present study.
Show in the study text Report a problemFND-3734225901
02HumanSystematic reviewEfficacy outcome
In a network meta-analysis in adults with NAFLD and T2DM, daily semaglutide ranked as the most effective drug for ALT (SUCRA 95.6%).
In plain wordsIn a network meta-analysis of adults with fatty liver and type 2 diabetes, daily semaglutide ranked best for lowering the liver enzyme ALT.
Peptide
Semaglutide
Outcome
DecreaseALT (SUCRA ranking)
Study
n: not reported in source
Comparator
Other interventions in the network
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Measurements
SUCRA
95.6%
ALT
Source sentences
Summary
Among five interventions (except exenatide (bid) and semaglutide (qw)) evaluated for AST outcome, and six interventions (except exenatide (bid)) evaluated for ALT outcome, semaglutide (qd) was the most effective drug (SUCRA (AST) = 100%, SUCRA (ALT) = 95.6%).
2 context sentences(design, population, supporting numbers)
Summary · context
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).
Summary · context
Fourteen RCTs involving 1666 participants were included in the present study.
Show in the study text Report a problemFND-3734225902

Studies that did not test the peptide alone9

In this study, the peptide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking the peptide.

03HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with NAFLD and T2DM, pooled daily GLP-1RAs (including liraglutide) reduced liver fat content (MD -3.66, 95% CI -5.56 to -1.76).
In plain wordsIn adults with fatty liver and type 2 diabetes, daily GLP-1 drugs as a group reduced liver fat.
Peptide
Liraglutide
Outcome
DecreaseLiver fat content, daily GLP-1RA group
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference, liver fat content
−3.66 NA
daily GLP-1RAs
Source sentences
Summary
The result of LFC in daily group was MD = -3.66, 95% CI [-5.56, -1.76] and in weekly GLP-1RAs group, it was MD = -3.51, 95% CI [-4, -3.02].
2 context sentences(design, population, supporting numbers)
Summary · context
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).
Summary · context
Fourteen RCTs involving 1666 participants were included in the present study.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-3734225903
04HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with NAFLD and T2DM, pooled daily GLP-1RAs (including liraglutide) reduced AST (MD -7.45, 95% CI -14.57 to -0.32).
In plain wordsIn adults with fatty liver and type 2 diabetes, daily GLP-1 drugs as a group lowered the liver enzyme AST.
Peptide
Liraglutide
Outcome
DecreaseAST, daily GLP-1RA group
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference, AST
−7.45 NA
daily GLP-1RAs
Source sentences
Summary
As to AST and ALT, the results in daily group versus weekly group were AST: MD = -7.45, 95% CI [-14.57, -0.32] versus MD= -0.58, 95% CI [-3.18, 2.01] and ALT: MD = -11.12, 95% CI [-24.18, 1.95] versus MD = -5.62, 95% CI [-15.25, 4].
2 context sentences(design, population, supporting numbers)
Summary · context
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).
Summary · context
Fourteen RCTs involving 1666 participants were included in the present study.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-3734225904
05HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with NAFLD and T2DM, pooled daily GLP-1RAs (including liraglutide) had an ALT mean difference of -11.12 (95% CI -24.18 to 1.95), which includes no effect.
In plain wordsIn adults with fatty liver and type 2 diabetes, daily GLP-1 drugs as a group did not clearly change the liver enzyme ALT.
Peptide
Liraglutide
Outcome
No significant changeALT, daily GLP-1RA group
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference, ALT
−11.12 NA
daily GLP-1RAs
Source sentences
Summary
As to AST and ALT, the results in daily group versus weekly group were AST: MD = -7.45, 95% CI [-14.57, -0.32] versus MD= -0.58, 95% CI [-3.18, 2.01] and ALT: MD = -11.12, 95% CI [-24.18, 1.95] versus MD = -5.62, 95% CI [-15.25, 4].
2 context sentences(design, population, supporting numbers)
Summary · context
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).
Summary · context
Fourteen RCTs involving 1666 participants were included in the present study.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-3734225905
06HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with NAFLD and T2DM, pooled daily GLP-1RAs (including semaglutide) reduced liver fat content (MD -3.66, 95% CI -5.56 to -1.76).
In plain wordsIn adults with fatty liver and type 2 diabetes, daily GLP-1 drugs as a group reduced liver fat.
Peptide
Semaglutide
Outcome
DecreaseLiver fat content, daily GLP-1RA group
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference, liver fat content
−3.66 NA
daily GLP-1RAs
Source sentences
Summary
The result of LFC in daily group was MD = -3.66, 95% CI [-5.56, -1.76] and in weekly GLP-1RAs group, it was MD = -3.51, 95% CI [-4, -3.02].
2 context sentences(design, population, supporting numbers)
Summary · context
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).
Summary · context
Fourteen RCTs involving 1666 participants were included in the present study.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3734225906
07HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with NAFLD and T2DM, pooled daily GLP-1RAs (including semaglutide) reduced AST (MD -7.45, 95% CI -14.57 to -0.32).
In plain wordsIn adults with fatty liver and type 2 diabetes, daily GLP-1 drugs as a group lowered the liver enzyme AST.
Peptide
Semaglutide
Outcome
DecreaseAST, daily GLP-1RA group
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference, AST
−7.45 NA
daily GLP-1RAs
Source sentences
Summary
As to AST and ALT, the results in daily group versus weekly group were AST: MD = -7.45, 95% CI [-14.57, -0.32] versus MD= -0.58, 95% CI [-3.18, 2.01] and ALT: MD = -11.12, 95% CI [-24.18, 1.95] versus MD = -5.62, 95% CI [-15.25, 4].
2 context sentences(design, population, supporting numbers)
Summary · context
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).
Summary · context
Fourteen RCTs involving 1666 participants were included in the present study.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3734225907
08HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with NAFLD and T2DM, pooled daily GLP-1RAs (including semaglutide) had an ALT mean difference of -11.12 (95% CI -24.18 to 1.95), which includes no effect.
In plain wordsIn adults with fatty liver and type 2 diabetes, daily GLP-1 drugs as a group did not clearly change the liver enzyme ALT.
Peptide
Semaglutide
Outcome
No significant changeALT, daily GLP-1RA group
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference, ALT
−11.12 NA
daily GLP-1RAs
Source sentences
Summary
As to AST and ALT, the results in daily group versus weekly group were AST: MD = -7.45, 95% CI [-14.57, -0.32] versus MD= -0.58, 95% CI [-3.18, 2.01] and ALT: MD = -11.12, 95% CI [-24.18, 1.95] versus MD = -5.62, 95% CI [-15.25, 4].
2 context sentences(design, population, supporting numbers)
Summary · context
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).
Summary · context
Fourteen RCTs involving 1666 participants were included in the present study.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3734225908
09HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with NAFLD and T2DM, pooled weekly GLP-1RAs (including semaglutide) reduced liver fat content (MD -3.51, 95% CI -4 to -3.02).
In plain wordsIn adults with fatty liver and type 2 diabetes, weekly GLP-1 drugs as a group reduced liver fat.
Peptide
Semaglutide
Outcome
DecreaseLiver fat content, weekly GLP-1RA group
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference, liver fat content
−3.51 NA
weekly GLP-1RAs
Source sentences
Summary
The result of LFC in daily group was MD = -3.66, 95% CI [-5.56, -1.76] and in weekly GLP-1RAs group, it was MD = -3.51, 95% CI [-4, -3.02].
2 context sentences(design, population, supporting numbers)
Summary · context
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).
Summary · context
Fourteen RCTs involving 1666 participants were included in the present study.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3734225909
10HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with NAFLD and T2DM, pooled weekly GLP-1RAs (including semaglutide) had an AST mean difference of -0.58 (95% CI -3.18 to 2.01), which includes no effect.
In plain wordsIn adults with fatty liver and type 2 diabetes, weekly GLP-1 drugs as a group did not clearly change the liver enzyme AST.
Peptide
Semaglutide
Outcome
No significant changeAST, weekly GLP-1RA group
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference, AST
−0.58 NA
weekly GLP-1RAs
Source sentences
Summary
As to AST and ALT, the results in daily group versus weekly group were AST: MD = -7.45, 95% CI [-14.57, -0.32] versus MD= -0.58, 95% CI [-3.18, 2.01] and ALT: MD = -11.12, 95% CI [-24.18, 1.95] versus MD = -5.62, 95% CI [-15.25, 4].
2 context sentences(design, population, supporting numbers)
Summary · context
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).
Summary · context
Fourteen RCTs involving 1666 participants were included in the present study.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3734225910
11HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with NAFLD and T2DM, pooled weekly GLP-1RAs (including semaglutide) had an ALT mean difference of -5.62 (95% CI -15.25 to 4), which includes no effect.
In plain wordsIn adults with fatty liver and type 2 diabetes, weekly GLP-1 drugs as a group did not clearly change the liver enzyme ALT.
Peptide
Semaglutide
Outcome
No significant changeALT, weekly GLP-1RA group
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Measurements
Mean difference, ALT
−5.62 NA
weekly GLP-1RAs
Source sentences
Summary
As to AST and ALT, the results in daily group versus weekly group were AST: MD = -7.45, 95% CI [-14.57, -0.32] versus MD= -0.58, 95% CI [-3.18, 2.01] and ALT: MD = -11.12, 95% CI [-24.18, 1.95] versus MD = -5.62, 95% CI [-15.25, 4].
2 context sentences(design, population, supporting numbers)
Summary · context
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).
Summary · context
Fourteen RCTs involving 1666 participants were included in the present study.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3734225911

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 4Current
21 Oct 2026, 18:59 UTC
Study data updated · source update from Europe PMC
Version 3
12 Oct 2026, 11:11 UTC
Study results updated
Version 2
9 Oct 2026, 03:06 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:05 UTC
First added · source update from Europe PMC

Comparing the effectiveness of long-term use of daily and weekly glucagon-like peptide-1 receptor agonists treatments in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus: a network meta-analysis.

Summary

Results from this study11

Studies that did not test the peptide alone9

Version history

Subjects

Publication types

MeSH terms

Keywords