Comparative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor and 4 glucagon-like peptide-1 (GLP-1) receptor agonist drugs in non-alcoholic fatty liver disease: A GRADE-assessed systematic review and network meta-analysis of randomized controlled trials.

Gu Y, Sun L, Zhang W, Kong T, Zhou R, He Y, Deng C, Yang L, Kong J, Chen Y, Shi J, Hu Y

Frontiers in pharmacology13 Mar 2023Cited by 29 (Europe PMC)

PMID36992825PMCIDPMC10040540DOI10.3389/fphar.2023.1102792PepBankPUB-36992825

Summary

Background: The relative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and 4 glucagon-like peptide-1 (GLP-1) receptor agonists for non-alcoholic fatty liver disease (NAFLD) therapy has not been sufficiently investigated. Methods: Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included. Primary outcomes were improvements in liver enzymes and liver fat parameters, while secondary outcomes included anthropometric measures, blood lipids and glycemic parameters. The frequentist method was used to perform a network meta-analysis. Evidence certainty was assessed using the grading of recommendations assessment, development, and evaluation (GRADE). Results: The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists). Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin. Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment. Conclusion: Semaglutide, liraglutide, and dapagliflozin all have a certain effect on NAFLD (or comorbid with type 2 diabetes) based on high confidence evidence from indirect comparisons, and semaglutide appears to have a therapeutic advantage over the other included medicines. Head-to-head studies are needed to provide more confidence in clinical decision-making.

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

Results from this study16

16 results from studies that gave the peptide. 16 results from people.

01HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found semaglutide lowered alanine aminotransferase (high certainty evidence).
In plain wordsIn people with fatty liver disease, a combined analysis of trials found semaglutide lowered the liver enzyme ALT.
Peptide
Semaglutide
Outcome
DecreaseAlanine aminotransferase
Study
n: not reported in source
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282501
02HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found semaglutide lowered aspartate aminotransferase (high certainty evidence).
In plain wordsIn people with fatty liver disease, a combined analysis of trials found semaglutide lowered the liver enzyme AST.
Peptide
Semaglutide
Outcome
DecreaseAspartate aminotransferase
Study
n: not reported in source
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282502
03HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found semaglutide lowered gamma-glutamyl transferase (high certainty evidence).
In plain wordsIn people with fatty liver disease, a combined analysis of trials found semaglutide lowered the liver enzyme GGT.
Peptide
Semaglutide
Outcome
DecreaseGamma-glutamyl transferase
Study
n: not reported in source
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282503
04HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found semaglutide lowered the controlled attenuation parameter, a liver fat measure (high certainty evidence).
In plain wordsIn people with fatty liver disease, a combined analysis of trials found semaglutide lowered a scan measure of liver fat.
Peptide
Semaglutide
Outcome
DecreaseControlled attenuation parameter
Study
n: not reported in source
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282504
05HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found liraglutide could lower alanine aminotransferase.
In plain wordsIn people with fatty liver disease, a combined analysis of trials found liraglutide could lower the liver enzyme ALT.
Peptide
Liraglutide
Outcome
DecreaseAlanine aminotransferase
Study
n: not reported in source
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282511
06HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found semaglutide lowered body weight (high certainty evidence).
In plain wordsIn people with fatty liver disease, a combined analysis of trials found semaglutide lowered body weight.
Peptide
Semaglutide
Outcome
DecreaseBody weight
Study
n: not reported in source
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282506
07HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found semaglutide lowered triglycerides (high certainty evidence).
In plain wordsIn people with fatty liver disease, a combined analysis of trials found semaglutide lowered triglycerides.
Peptide
Semaglutide
Outcome
DecreaseTriglycerides
Study
n: not reported in source
Analysis
Secondary
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282508
08HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis listed high-density lipoprotein-cholesterol among outcomes that semaglutide could lower (high certainty evidence).
In plain wordsIn people with fatty liver disease, a combined analysis of trials listed HDL cholesterol among measures semaglutide could lower.
Peptide
Semaglutide
Outcome
DecreaseHDL cholesterol
Study
n: not reported in source
Analysis
Secondary
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282509
09HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found semaglutide lowered glycosylated hemoglobin (high certainty evidence).
In plain wordsIn people with fatty liver disease, a combined analysis of trials found semaglutide lowered HbA1c.
Peptide
Semaglutide
Outcome
DecreaseGlycosylated hemoglobin
Study
n: not reported in source
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282510
10HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found liraglutide could lower subcutaneous adipose tissue.
In plain wordsIn people with fatty liver disease, a combined analysis of trials found liraglutide could lower subcutaneous fat tissue.
Peptide
Liraglutide
Outcome
DecreaseSubcutaneous adipose tissue
Study
n: not reported in source
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282512
11HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found liraglutide could lower body mass index.
In plain wordsIn people with fatty liver disease, a combined analysis of trials found liraglutide could lower BMI.
Peptide
Liraglutide
Outcome
DecreaseBody mass index
Study
n: not reported in source
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282513
12HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found liraglutide could lower fasting blood glucose.
In plain wordsIn people with fatty liver disease, a combined analysis of trials found liraglutide could lower fasting blood sugar.
Peptide
Liraglutide
Outcome
DecreaseFasting blood glucose
Study
n: not reported in source
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282514
13HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found liraglutide could lower glycosylated hemoglobin.
In plain wordsIn people with fatty liver disease, a combined analysis of trials found liraglutide could lower HbA1c.
Peptide
Liraglutide
Outcome
DecreaseGlycosylated hemoglobin
Study
n: not reported in source
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282515
14HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found liraglutide could lower glucose and homeostasis model assessment.
In plain wordsIn people with fatty liver disease, a combined analysis of trials found liraglutide could lower a measure of insulin resistance.
Peptide
Liraglutide
Outcome
DecreaseHomeostasis model assessment of insulin resistance
Study
n: not reported in source
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282516
15HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found semaglutide lowered liver stiffness (high certainty evidence).
In plain wordsIn people with fatty liver disease, a combined analysis of trials found semaglutide lowered liver stiffness.
Peptide
Semaglutide
Outcome
DecreaseLiver stiffness measurement
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282505
16HumanSystematic reviewEfficacy outcome
In patients with NAFLD, network meta-analysis found semaglutide lowered systolic blood pressure (high certainty evidence).
In plain wordsIn people with fatty liver disease, a combined analysis of trials found semaglutide lowered systolic blood pressure.
Peptide
Semaglutide
Outcome
DecreaseSystolic blood pressure
Study
n: not reported in source
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included.
Summary · context
The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists).
Show in the study text Report a problemFND-3699282507

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

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 3Current
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

Comparative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor and 4 glucagon-like peptide-1 (GLP-1) receptor agonist drugs in non-alcoholic fatty liver disease: A GRADE-assessed systematic review and network meta-analysis of randomized controlled trials.

Summary

Results from this study16

Version history

Subjects

Publication types

Keywords