GLP‐1 analogs and regional adiposity: A systematic review and meta‐analysis

Abstract

Background: Glucagon-like peptide 1 (GLP-1) analogs regulate body weight and liver steatosis. Different body adipose tissue (AT) depots exhibit biological variability.Accordingly, GLP-1 analog effects on AT distribution are unclear.Objectives: To investigate GLP1-analog effects on adiposity distribution.Search methods: PubMed, Cochrane, and Scopus databases were screened for eligible randomized human trials. Pre-defined endpoints included visceral AT (VAT), subcutaneous AT (SAT), total AT (TAT), epicardial AT (EAT), liver AT (LAT), and waistto-hip ratio (W:H). Search was conducted until May 17, 2022.Data collection and analysis: Data extraction and bias assessment were performed by two independent investigators. Treatment effects were estimated using random effects models. Analyses were performed on Review Manager v5.3.Main results: Out of the 367 screened studies, 45 were included in the systematic review and 35 were used in the meta-analysis. GLP-1 analogs reduced VAT, SAT, TAT, LAT, and EAT, with non-significant effects on W:H. Overall bias risk was low.Conclusions: GLP-1 analog treatment reduces TAT, affecting most studied AT depots, including the pathogenic VAT, EAT, and LAT. GLP-1 analogs may have significant roles in combating metabolic, obesity-associated diseases via reductions of key AT depot volumes.

Pathophysiological Mechanisms and Clinical Associations of Non-Alcoholic Fatty Pancreas Disease

“…Glucagon-like peptide-1 (GLP-1) agonists have the potential to lessen the severity of NAFPD, by modulating the ER stress pathway and the subsequent signaling of apoptosis in mice models, and to alter regional adiposity in humans. 121,122 Moreover, the synergistic activity of sitagliptin, a dipeptidyl peptidase (DPP) 4 inhibitor which prolongs the action of GLP-1 and insulin secretion from pancreatic β-cells, with telmisartan, which modulates inflammatory responses and improves endothelial function, exhibits remarkable efficacy in effectively managing the progression of NAFPD in mice. 123 Based on evidence from experimental models, GLP-1 agonists consist the most promising class of drugs for the treatment of NAFPD122 and prospective trials are needed to verify these data.…”

Comparative effectiveness of glucagon-like peptide-1 receptor agonists on body composition and anthropometric indices: A protocol for a systematic review and network meta-analysis of randomized controlled trials

“…Evidence supports that a decrease in visceral fat tissue can ameliorate obesity-related metabolic complications [1,6]. Previous systematic reviews found that GLP1-RAs significantly reduced adiposity (i.e., visceral, subcutaneous, and epicardial fat) [13][14][15]. However, these systematic reviews did not simultaneously compare individual GLP1-RAs therapy or different dosage regimens among overweight or obese persons with or without type 2 diabetes [13][14][15].…”

“…However, there are several limitations regarding the currently available systematic review and meta-analysis of GLP1-RAs among adult overweight or obese persons. These include the following: (i) most of existing reviews focused mainly on glycemic control and weight reduction, in which not comprehensive to body composition and anthropometric indices outcome [ 12 , 16 , 17 ]; (ii) the effect estimates are based on the synthesis of a combination of medication class therapy (pairwise meta-analysis) rather than comparison among individual GLP1-RAs therapy [ 13 – 15 ]; and (iii) studies being based on mixed populations or focused on particular population (i.e., nonalcoholic fatty liver disease or polycystic ovary syndrome) [ 8 , 9 , 11 , 12 , 15 ]. In this regard, no systematic review has compared individual GLP1-RAs therapy or different dosage regimens among overweight or obese persons with or without type 2 diabetes.…”

“…To date, promising pharmacologic treatment options for overweight or obese persons have become available, particularly a class of medication that improved glucose-mediated insulin secretion-namely glucagon-like peptide-1 receptor agonists (GLP1-RAs) [7]. Besides glycemic control and promotion of weight loss among diabetes and non-diabetes populations [7][8][9][10][11][12], existing clinical trials and previous systematic reviews also illustrated that GLP1-RAs have further benefits on change in body composition and anthropometric indices (i.e., visceral, subcutaneous, epicardial fat mass, BMI, and waist circumference) [8, [12][13][14][15].…”