The effects of glucagon-like peptide-1 receptor agonists on glycemic control and anthropometric profiles among diabetic patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials

Nowrouzi-Sohrabi, Peyman; Rezaei, Shahla; Jalali, Mohammad; Ashourpour, Mahkameh; Ahmadipour, Ahmad; Keshavarz, Pedram; Akbari, Hamed

doi:10.1016/j.ejphar.2020.173823

Cited by 9 publications

(14 citation statements)

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“…GLP-1 RAs are incretin hormones secreted by intestinal Lcells following meal ingestion, and have various metabolic functions, including: 1) inducing b-cell proliferation and reducing lipotoxic b-cell apoptosis; 2) enhancing both insulin synthesis and glucose-stimulated insulin secretion; 3) inhibiting glucagon secretion in a glucose-dependent manner; 4) reducing IR and improving peripheral insulin sensitivity through promoting weight loss caused by delayed gastric emptying and appetite suppression; and 5) increasing liver and muscle glucose uptake, followed by lowering of free fatty acid levels (34)(35)(36)(37). A recent meta-analysis, concerning the use of GLP-1 RAs in patients with NAFLD (12 studies involving 780 patients), found significant improvements in FBS levels and HOMA-IR when the trial lasted longer than 24 weeks in subgroup analysis (38), similar to the results of our analysis. However, few studies have focused on the improvement in IR.…”

Section: Discussionmentioning

confidence: 99%

GLP-1 RAs and SGLT-2 Inhibitors for Insulin Resistance in Nonalcoholic Fatty Liver Disease: Systematic Review and Network Meta-Analysis

Yan

Shen

et al. 2022

Front. Endocrinol.

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ObjectiveGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce glycaemia and weight and improve insulin resistance (IR) via different mechanisms. We aim to evaluate and compare the ability of GLP-1 RAs and SGLT-2 inhibitors to ameliorate the IR of nonalcoholic fatty liver disease (NAFLD) patients.Data SynthesisThree electronic databases (Medline, Embase, PubMed) were searched from inception until March 2021. We selected randomized controlled trials comparing GLP-1 RAs and SGLT-2 inhibitors with control in adult NAFLD patients with or without T2DM. Network meta-analyses were performed using fixed and random effect models, and the mean difference (MD) with corresponding 95% confidence intervals (CI) were determined. The within-study risk of bias was assessed with the Cochrane collaborative risk assessment tool RoB.Results25 studies with 1595 patients were included in this network meta-analysis. Among them, there were 448 patients, in 6 studies, who were not comorbid with T2DM. Following a mean treatment duration of 28.86 weeks, compared with the control group, GLP-1 RAs decreased the HOMA-IR (MD [95%CI]; -1.573[-2.523 to -0.495]), visceral fat (-0.637[-0.992 to -0.284]), weight (-2.394[-4.625 to -0.164]), fasting blood sugar (-0.662[-1.377 to -0.021]) and triglyceride (- 0.610[-1.056 to -0.188]). On the basis of existing studies, SGLT-2 inhibitors showed no statistically significant improvement in the above indicators. Compared with SGLT-2 inhibitors, GLP-1 RAs decreased visceral fat (-0.560[-0.961 to -0.131]) and triglyceride (-0.607[-1.095 to -0.117]) significantly.ConclusionsGLP-1 RAs effectively improve IR in NAFLD, whereas SGLT-2 inhibitors show no apparent effect.Systematic Review RegistrationPROSPERO https://www.crd.york.ac.uk/PROSPERO/, CRD42021251704

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Section: Discussionmentioning

confidence: 99%

GLP-1 RAs and SGLT-2 Inhibitors for Insulin Resistance in Nonalcoholic Fatty Liver Disease: Systematic Review and Network Meta-Analysis

Yan

Shen

et al. 2022

Front. Endocrinol.

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“…Thus, GLP-1RAs bring hope to obese people. GLP-1RAs were originally developed to control blood glucose, but almost all clinical trials containing GLP-1RAs have found that they have a weight-loss effect, and some studies have focused on evaluating the weight-loss effect of GLP-1RAs in various types of obese people (e.g., GLP-1RAs have produced positive results in individuals with polycystic ovary syndrome) (26,27). Previous studies on the cost effectiveness of GLP-1Ras have focused on glycemic control in diabetic patients (15), but this study is the first to conduct an economic analysis on the weight-loss effects of multiple GLP-1RAs.…”

Section: Discussionmentioning

confidence: 99%

Cost-effectiveness analysis of 4 GLP-1RAs in the treatment of obesity in a US setting

Hu¹,

Zheng²,

Ye³

et al. 2022

Ann Transl Med

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Background: The number of obese people continues to increase worldwide, and obesity-related complications add to every country's health burden. Consequently, new weight-loss medications, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), are attracting increasing attention. This study sought to assess the cost effectiveness for weight loss of 4 GLP-1RAs in adult patients with obesity in the United States.Methods: Four GLP-1RA groups that received Liraglutide (1.8 mg QD), Semaglutide (1.0 mg QW), Dulaglutide (1.5 mg QW), or Exenatide (10 μg BID), and one no-treatment group were compared using a decision-tree model. All the estimated parameters were derived from published articles. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were adopted as the study endpoints.We analyzed the results with the willingness-to-pay (WTP) threshold, and conducted deterministic and probabilistic sensitivity analyses. Results:The GLP-1RAs produced effective weight-loss results; however, not all the GLP-1RAs were cost effective compared to no treatment based on a WTP threshold of $195000/QALY. Among the 4 GLP-1RAs, Semaglutide provided a cost-effective strategy with an ICER of $135467/QALY. The sensitivity analyses showed that these results are reliable.Conclusions: Among the 4 GLP-1RAs, Semaglutide was the most cost-effective obesity medication.

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“…The third class is GLP-1R agonist, 71,73,74,79,114,119,126 the effect of this class may provide a protective role in the ceased progression of MAFLD (Table 2), and it is reported that GLP-1R may have much stronger benefit on the reduction of IR in MAFLD compared with other ADA. 126 Zafar et al 71 (10 studies, 5 studies, 4 studies, 2 studies) also confirmed the aforementioned benefits of GLP-1R agonists on the management of MAFLD, based on significant improvement of liver function test, including AST (WMD: −3.29), ALT (WMD: −9.92), GGT (WMD: −12.38), and FIB-4 (WMD: −0.15), suggesting that DM patients who take GLP-1R agonists also have extraglycemic benefits on MAFLD.…”

Section: Strategy For Targeting Dm and Mafld Simultaneously: Adamentioning

confidence: 99%

“…115 So far, evidence, including randomized controlled trials (RCTs), review, and meta-analyses shows at least three classes of ADA, such as insulin sensitizers (metformin and thiazolidinediones), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonist (GLP-1R agonist), and so on that may have favorable effects on the spectrum of MAFLD (Table 1). 27,28,30,63,65,67,69,71–84,87,96–98,101,102,108–110,112–114,116,117…”

Section: Strategy For Targeting Dm and Mafld Simultaneously: Adamentioning

confidence: 99%

“…The literature involving in MAFLD can be found everywhere. 13,65–89 In brief, MAFLD, characterized by the fat accumulation >5% (by histological examination) or >5.6% (by magnetic resonance imaging (MRI)-derived proton density fat fraction [MRI-PDFF]) of hepatocytes (presence of steatosis) without excessive alcohol consumption or secondary causes of hepatic steatosis, presents a biggest health hazard globally, based on its potential continuous progression to advanced liver fibrosis (liver cirrhosis) and finally the development of hepatocellular carcinoma (HCC), contributing to the heavy economic and social burdens worldwide. 65–67,88,90–100…”

Section: Metabolic Dysfunction-associated Fatty Liver Diseases (Also ...mentioning

confidence: 99%

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To Do One and To Get More: Part II. Diabetes and metabolic dysfunction-associated fatty liver diseases

Lee

Wang

Yang

et al. 2022

Journal of the Chinese Medical Association

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Type 2 diabetes mellitus (DM) is characterized by inability of faulty pancreatic β-cells to secret a normal amount of insulin to maintain normal body consumption, and/or peripheral tissue has a decreased susceptibility to insulin, resulting in hyperglycemia and insulin resistance. Similar to other chronic systemic inflammatory diseases, DM is a result from dysregulated interactions between ethnic, genetic, epigenetic, immunoregulatory, hormonal, and environmental factors. Therefore, it is rational to suppose the concept as “To do one and to get more”, while using antidiabetic agents (ADA), a main pharmacologic agent for the treatment of DM, can provide an extraglycemia effect on comorbidities or concomittent comorbidities to DM. In this review, based on the much strong correlation between DM and metabolic dysfunction-associated fatty liver diseases (MAFLD) shown by similar pathophysiological mechanisms and a high prevalence of DM in MAFLD and its vice versa (a high prevalence of MAFLD in DM), it is possible to use the strategy to target both diseases simultaneously. We focus on a new classification of ADA, such as glucagon-like peptide-1 receptor (GLP1R) agonist and sodium-glucose cotransporter-2 (SGLT-2) inhibitors to show the potential benefits of extraglycemic effect on MAFLD. We conclude that the management of DM patients, especially for those who need ADA as adjuvant therapy should include healthy lifestyle modification to overcome the metabolic syndrome, contributing to the urgent need of an effective weight-reduction strategy. GLP1R agonist is one of effective body weight-lowering medications, which may be a better choice for DM complicated with MAFLD or its-associated severe form as metabolic associated steatohepatitis (MASH), although the role of SGLT-2 inhibitors is also impressive. The prescription of these two classes of ADA may satisfy the concept “To do one and to get more”, based on successful sugar-lowering effect for controlling DM and extraglycemia benefits of hepatoprotective activity in DM patients.

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The effects of glucagon-like peptide-1 receptor agonists on glycemic control and anthropometric profiles among diabetic patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials

Cited by 9 publications

References 50 publications

GLP-1 RAs and SGLT-2 Inhibitors for Insulin Resistance in Nonalcoholic Fatty Liver Disease: Systematic Review and Network Meta-Analysis

GLP-1 RAs and SGLT-2 Inhibitors for Insulin Resistance in Nonalcoholic Fatty Liver Disease: Systematic Review and Network Meta-Analysis

Cost-effectiveness analysis of 4 GLP-1RAs in the treatment of obesity in a US setting

To Do One and To Get More: Part II. Diabetes and metabolic dysfunction-associated fatty liver diseases

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