Effect of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors and their combination on carotid intima-media thickness

Abstract Background/Introduction Type 2 diabetes mellitus (T2DM) is an additional factor for exacerbation of atherosclerosis increasing the risk for ischemic attacks such as coronary artery disease and ischemic stroke. Evaluation of carotid artery atherosclerosis through ultrasound techniques is a useful tool for risk stratification in type 2 diabetic patients. Purpose We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on carotid intima-media thickness (cIMT) of T2DM patients. Methods A total of 320 T2DM patients were randomized to receive insulin (n = 80), liraglutide (n = 80), empagliflozin (n = 80) or their combination (GLP-1RA+SGLT-2i) (n = 80) as add-on to metformin. At baseline, at 6 and at 12 months of treatment, we measured the maximal thickness of six major points including right and left common carotid, carotid bifurcation and internal carotids. Finally, we calculated the average cIMT of all six segments (three on each side) to get mean cIMT. Results Compared to baseline, all patients had significantly reduced cIMT at 6 and at 12 months of treatment (p < 0.001; Table). A significant interaction of follow-up time with the type of treatment was observed regarding cIMT levels (F = 7.203, p for interaction < 0.001) in a model including age, sex, smoking, baseline body mass index, glucose levels, glycosylated hemoglobin, levels of blood lipids and their changes at 6 and 12 months of treatment as covariates. At 6 months, patients who were treated with GLP-1RA, SGLT-2i and those under the combination GLP-1RA+SGLT-2i showed a greater reduction of cIMT (-2.5%, -2.4% and -5.8%) compared to insulin (-0.8%; p = 0.008, p = 0.022, and p < 0.001, respectively). Moreover, at 12 months patients under GLP-1RA, SGLT-2i and their combination achieved remarkable reduction of cIMT (-7.4%, -4.9% and -10%) than those under insulin (-1.7%, p < 0.001 for all comparisons). Conclusions Twelve-month treatment with GLP-1RA, SGLT-2i and their combination resulted in reduction of cIMT in T2DM. The combined treatment was superior and additive to each regimen separately.Table