Metformin and diphenyleneiodonium reduce pathological changes induced by high glucose and advanced glycation end products in a microphysiological arterial model, while atorvastatin alters only endothelial cell morphology.

Too much sugar and sticky sugar-protein waste in the blood cause cells in artery walls to produce harmful molecules called reactive oxygen species. These molecules destroy a key signaling chemical called nitric oxide, which keeps blood vessels flexible and healthy. Two drugs stop this damage: one blocks the main source of the harmful molecules inside the cell's energy factories, and the other blocks a different enzyme that also makes these molecules. This lets nitric oxide work properly again, preventing the artery walls from becoming stiff and damaged. A third drug only changes the shape of the surface cells by altering their internal scaffolding, but does not stop the sugar-related damage.