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

Abstract

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.

Does Therapy with Glucagon-like Peptide 1 Receptor Agonists Have an Effect on Biochemical Markers of Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD)? Pleiotropic Metabolic Effect of Novel Antidiabetic Drugs in Patients with Diabetes—Interventional Study

“…Also Kovalic AJ et al in their meta-analysis proved that semaglutide is one of the most effective drugs to treat NAFLD, which was confirmed by elastography and non-invasive blood tests [ 48 ]. The same results were published in 2023 by Gu Y et al [ 49 ] Similar results to our study on FIB-4 decrease were obtained by Arai, T et al in their pilot study for oral semaglutide treatment [ 50 ]. Also, Carretero-Gómez J et al obtained a statistically significant decrease in the FIB-4 value [ 51 ].…”

Current Therapeutical Approaches Targeting Lipid Metabolism in NAFLD

“…At the moment, though, it seems that semaglutide is not effective in resolving or ameliorating liver fibrosis once it is present [ 125 ], whereas it seems to decrease steatosis and liver inflammation in vivo in Ldrl −/− mice [ 126 ]. Comparative studies and meta-analyses are currently being carried out in order to identify the most effective drug and its posology, which seems to also vary according to the patients’ metabolic status and compliance [ 127 , 128 , 129 , 130 ].…”

Therapie des Typ-2-Diabetes

“…Beide Messparameter verbesserten sich unter SGLT-2-Inhibitoren im Vergleich zu anderen Antidiabetika signifikant, wobei längerfristige RCTs fehlen. In der umfangreichen Analyse von Gu et al bei Patienten mit Typ-2-Diabetes und NAFLD [215] fanden sich positive Effekte auf die Leberfunktion (Alanin-Aminotransferase, Aspartat-Aminotransferase, γ-Glutamyl-Transferase) und auf morphologische Parameter der Lebersteatose (LSM, CAP) unter der Therapie mit Dapagliflozin und GLP-1-RAs. Zu vergleichbaren Ergebnissen in Bezug auf SGLT-2-Hemmer kamen die Autoren auch in einem weiteren systematischen Review, wobei die Daten aufgrund der Kürze der Untersuchungen und den Studiengrößen noch keine endgültigen Schlüsse zulassen [216].…”