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.