<h4>Context</h4>It has been suggested that consumption of saccharin, a widely used artificial sweetener, decreases insulin sensitivity in rodents and humans, but studies show conflicting results.<h4>Objective</h4>To investigate if saccharin affects insulin sensitivity in a proof-of-concept study in humans using hyperinsulinemic-euglycemic clamp.<h4>Methods</h4>In an open-label pilot study, we recruited 14 overweight participants without diabetes who were mean 60.5 (SD 4.1) years of age and had a body mass index of 27.6 (SD 0.7). Here, INS is linked to diabetes mellitus.