Effect of glucagon‐like peptide‐1 receptor agonists on fat distribution in patients with type 2 diabetes: A systematic review and meta‐analysis

Abstract

Aims/Introduction Glucagon‐like peptide‐1 receptor agonists (GLP‐1Ras) are widely used to treat type 2 diabetes. They not only reduce glucose, but also have a positive effect on weight loss. However, few studies have reported the effect of GLP‐1Ras on fat distribution. Materials and Methods PubMed, Cochrane, Embase and ClinicalTrials.gov were searched for randomized controlled trials on GLP‐1Ras and type 2 diabetes, published from inception to June 2021. Our main outcomes were the reductions of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Other anthropometric outcomes were also assessed. We used the Cochrane Collaboration tools to assess the risk of bias in the included studies. The quality of the evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation profiler version 3.6. Review Manager 5.4.1 and Stata 16.0 were used for data analysis. Results A total of 10 studies involving 541 patients were included. Compared with the control groups, the GLP‐1Ras groups showed reductions in VAT (standard mean difference −0.54, 95% confidence interval [CI] −0.92, −0.17, I 2 = 79%, P = 0.005) and SAT (standard mean difference −0.44, 95% CI −0.60, −0.27, I 2 = 44%, P < 0.00001). In addition, bodyweight (weighted mean difference −3.59, 95% CI −4.30, −2.88, I 2 = 0%, P < 0.00001), waist circumference (weighted mean difference −3.09, 95% CI −4.66, −1.52, I 2 = 70%, P = 0.0001) and body mass index (weighted mean difference −1.11, 95% CI −1.35, −0.86, I 2 = 47%, P < 0.00001) were significantly decreased. According to the Grades of Recommendation, Assessment, Development and Evaluation approach, the level of evidence was low or moderate. Conclusion This study highlights that GLP‐1Ras, especially liraglutide and exenatide, might play an active role in fat distribution in patients with type 2 diabetes. After treatment with GLP‐1Ras, both VAT and SAT decreased, and the decrease of VAT was numerically greater than that of SAT.

Safety and efficacy of liraglutide on reducing visceral and ectopic fat in adults with or without type 2 diabetes mellitus: A systematic review and meta‐analysis

“…Our safety findings on liraglutide are consistent with those of a previous meta‐analysis 10 . None of the included studies reported adverse hypoglycaemic events or hepatic or renal insufficiency following therapy with liraglutide.…”

“…Our results are consistent with those of a previous meta-analysis that included patients with T2DM. 10 However, we provide an explanation for the cardiometabolic benefits of liraglutide in obese and overweight patients without T2DM.…”

“…In patients with metabolic syndrome, inflammatory mediators released from EAT play a potential role in increasing the prevalence and severity of cardiovascular disease 26 . A previous meta‐analysis has shown that treatment with GLP‐1 RA significantly reduces VAT, SAT 10 and liver fat 28 in patients with T2DM. To our knowledge, no meta‐analyses have focused on the effect of liraglutide on visceral and ectopic fat in patients without T2DM.…”

“…Therefore, for a comprehensive evaluation of these conflicting data, a meta‐analysis is required. A recent meta‐analysis evaluated the effect of GLP‐1 RA on fat distribution in patients with T2DM 10 . However, reduction of visceral and ectopic fat not only provides cardiovascular benefits in patients with T2DM, but also in those with other obesity‐related conditions, including polycystic ovary syndrome, metabolic syndrome and schizophrenia spectrum disorders 2 .…”

Updates of incretin‐related drugs for the treatment of type 2 diabetes

“…GLP‐1 RAs lower glucose levels by direct and indirect actions on several organs, including the central nervous system, heart, arteries, kidneys, liver and pancreas 13 . A recent systematic review and meta‐analysis 14 also showed that GLP‐1RAs significantly reduce both visceral adipose tissue and subcutaneous adipose tissue, and the decrease of visceral adipose tissue was greater than that of subcutaneous adipose tissue when compared with the control group.…”