Glucagon‐like peptide‐1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomised controlled trials

Abstract

Aim: To conduct a meta-analysis and systematic review to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on clinical biomarkers of inflammation and oxidative stress in patients with type 2 diabetes.Methods: Medline, Embase and the Cochrane Library were searched for randomised controlled trials (RCTs) that examined changes with GLP-1RAs in a priori selected biomarkers of inflammation: C-reactive protein (CRP), adiponectin, tumour necrosis factor-alpha (TNFα), plasminogen activator inhibitor-1, interleukin-6, leptin; and of oxidative stress: malondialdehyde (MDA); 8-iso-prostaglandin F2α; and 8-hydroxy-2 0 -deoxyguanosine (8-OHdG). Results: We included 40 eligible RCTs (n = 6749) with a median follow-up of 6 months, a mean participant age of 53.1 years, 56.3% females, glycated haemoglobin (HbA1c) 55.6 mmol/mol, body mass index 28.8 kg/m 2 and diabetes duration 7.46 years. Analysis of GLP-1RAs versus standard diabetes therapies or placebo revealed significant reductions in CRP, TNFα and MDA, and significant increases in adiponectin for (mean difference À0.54 mg/L [À0.75, À0.34]; standard mean difference [SMD] À0.39 [À0.62, À0.15]; SMD À0.84 [À1.61, À0.06] and SMD 0.30 [0.12, 0.49], respectively [95% confidence intervals]). Systolic blood pressure decreased significantly and was significantly and strongly correlated with a reduction in CRP. Homeostatic model assessment of insulin resistance was also significantly correlated with a reduction in CRP, but HbA1c was not. Conclusions: There is strong evidence supporting clinically relevant antiinflammatory and antioxidant effects of GLP-1RAs. This may be used to guide future targeted clinical use of GLP-1RAs and the development of medications seeking to target the cardioprotective properties of GLP-1RAs. * Jonathan J. H. Bray and Harri Foster-Davies are co-first authors.

Risk of diabetic macular oedema with sodium‐glucose cotransporter‐2 inhibitors in type 2 diabetes patients: A multi‐institutional cohort study in Taiwan

“…One pathophysiology of DMO consists of an inflammatory pathway, 38,45 and previous studies have indicated that diabetic patients with progression of renal dysfunction are associated with elevated serum interleukin (IL)‐6 and IL‐8 levels 46‐48 . Although both SGLT2 inhibitors and GLP‐1RAs could decrease systemic inflammation, 14,49 SGLT2 inhibitors may have more anti‐inflammatory effects in patients with renal dysfunction, based on our findings. Future investigations should confirm this observation and the hypothesis.…”

“…One pathophysiology of DMO consists of an inflammatory pathway, 38,45 and previous studies have indicated that diabetic patients with progression of renal dysfunction are associated with elevated serum interleukin (IL)-6 and IL-8 levels. [46][47][48] Although both SGLT2 inhibitors and GLP-1RAs could decrease systemic inflammation, 14,49…”

Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation

“…Linagliptin, a DPP-4 inhibitor, has been shown to prevent these unfavorable effects, along with decreasing PAI-1 gene expression in endothelial cells [ 121 ]. Additionally, both vildagliptin and sitagliptin have been reported to decrease PAI-1 [ 122 , 123 ] levels in T2DM patients, in contrast to glucagon-like peptide-1 receptor agonists [ 124 ]. In a randomized trial, a 12-months long treatment with empagliflozin (10 mg/day, n = 31) has resulted in 25% decrease in PAI-1 concentration when compared with standard therapy [ 125 ].…”

“…This has been however attributed to the synergistic action on glucose metabolism, the weight loss and changes in leptin concentrations [ 125 ]. In polycystic ovary syndrome, exenatide was shown to decrease lysis time, without having any effect on clot density [ 124 ]. However, to date, there have been no reports on the effect of the new antidiabetic drugs on clot lysis time in patients with T2DM.…”

GLP-1 based therapies and disease course of inflammatory bowel disease

“…In the gut, GLP-1 may control inflammation through binding to GLP-1 receptors on intestinal intraepithelial lymphocytes [11] . In favour of a clinically relevant role of GLP-1 in reducing systemic inflammation, a meta-analysis of randomised clinical trials concluded that GLP-1 receptor agonists reduce circulating levels of inflammatory biomarkers, including C-reactive protein and tumour necrosis factor (TNF)-α [12] . The clinical impact of GLP-1 in gut inflammation, however, remains uncertain.…”