Effects of Semaglutide and Empagliflozin on Inflammatory Markers in Patients with Type 2 Diabetes

Abstract

Low-grade inflammation is associated with complications of type 2 diabetes. Glucagon-like peptide-1 receptor agonists and sodium-glucose transporter-2 inhibitors have shown cardioprotective effects that are independent of their glucose-lowering effects. Cardio-protection could be mediated by the anti-inflammatory effects of these medications, but there is currently limited evidence to support this hypothesis. We conducted a prospective clinical study in patients with type 2 diabetes requiring treatment intensification. Ten patients were assigned to receive empagliflozin 10 mg and 10 patients to receive s/c semaglutide (titrated to 1 mg once a week) in a non-randomised manner. All parameters were measured at baseline and after 3 months. Fasting plasma glucose and glycated haemoglobin improved significantly in both treatment groups, with no between-group differences. Body weight and body mass index reduced significantly more in the semaglutide group, whereas waist circumference decreased only in the empagliflozin group. There was a trend for high-sensitivity CRP reduction in both treatment groups that did not reach statistical significance. Interleukin-6 and the neutrophil-to-lymphocyte ratio did not change in either group. Ferritin and uric acid decreased significantly only in the empagliflozin group, and ceruloplasmin decreased significantly only in the semaglutide group. Though there were clinically meaningful improvements in diabetes control in both treatment arms, we could detect only minor changes in some inflammatory markers.

Fasting GLP-1 Levels and Albuminuria Are Negatively Associated in Patients with Type 2 Diabetes Mellitus

“…As the benefit of a decline in estimated GFR was not statistically significant and less notable compared to the impact observed with SGLT-2 inhibitors [ 30 , 31 ], this effect could mostly be attributed to a reduction in albuminuria. Moreover, GLP-1 RAs exhibit favorable outcomes [ 32 ] in reducing inflammation [ 33 ], managing obesity [ 34 ], protecting pulmonary function [ 35 ], and restoring gut microbiome composition [ 36 ].…”

Anti-inflammatory benefits of semaglutide: State of the art

“…This effect may contribute to a reduction in systemic inflammation and potentially lower the risk of cardiovascular disorders [63] . A more recent clinical study reported anti-inflammatory effects of semaglutide (1 mg/week) in patients with T2DM, although these effects were not significant after 3 months [64] . Furthermore, a meta -analysis examining the effects of semaglutide on the inflammatory cytokine high-sensitive C-reactive protein (hsCRP) found a significant reduction in its levels in patients with T2DM [74] .…”

“…While semaglutide is primarily known for its metabolic benefits, such as regulating glucose levels, promoting weight loss, and normalizing lipid profiles, there is emerging evidence suggesting that it may also have additional anti-inflammatory effects [20] , [62] . In fact, there is strong evidence indicating that semaglutide can modulate or reduce inflammatory processes [63] , [64] , [65] . Considering that inflammation is a key factor in many diabetic complications, these anti-inflammatory effects of semaglutide could provide additional benefits, particularly in the cardiovascular system [66] .…”

“… Semaglutide 40 men with DM 1 mg/week/6 months/injection Reduced the inflammatory cytokines of TNF-α and IL-6 [63] Semaglutide 20 patients with T2DM 1 mg/week/3 months/injection Minor changes in some inflammatory cytokines (not meaningful) e.g. CRP and IL-6 [64] Semaglutide Patients with T2DM – Semaglutide is associated to reduced levels of hsCRP vs baseline in patients with T2DM [74] Semaglutide Obese patients with T2DM 0.25 mg/week for 4 weeks, increased to 0.50 mg/week for 16 weeks, and then to 1 mg/week for 10 months Semaglutide improved psoriasis and epicardial fat volume and inflammation [89] Semaglutide Patients with T2DM and CKD 3 mg/day/9months/orally Semaglutide improved renal function probably by lowering inflammation [65] Semaglutide Epicardial fat biopsies of patients undergoing open-heart surgery – Semaglutide reduced the neutrophils adhesion into endothelial cells and enhances the angiogenesis process [67] Semaglutide Epicardial fat biopsies of patients undergoing cardiac surgery – Semaglutide induced anti-thrombotic and anti-atherosclerotic effects by suppressing neutrophils’ activity [87] …”

Effects of Semaglutide in Doxorubicin-Induced Cardiac Toxicity in Wistar Albino Rats

“…In an animal model of acute inflammation, semaglutide decreased the levels of plasma markers of systemic inflammation, downregulated multiple inflammatory pathways compared to controls, and was associated with a significant reduction in plaque lesion development, 9 while other findings revealed only minor changes in some inflammatory markers. 10 …”