Endoscopic placement of the duodenal-jejunal bypass liner (DJBL) in morbidly obese patients induces significant weight loss. Additionally, early studies reported significant improvements in several parameters of glucose homeostasis in morbidly obese patients with T2DM. The observed glycemic control occurred soon after device placement, after a minimal weight loss, suggesting the activation of weight loss-independent anti-diabetic mechanisms of glucose normalization. This effect is associated with favorable changes in hormones involved in glucose level regulation. Recently, larger clinical studies, focused primarily on the effect of the DJBL on T2DM treatment, have corroborated initial observations not only in morbidly obese patients but in non-morbidly obese diabetic patients as well. In this article we review the evidence from preclinical animal and clinical human studies that support the efficacy of DJBL to treat T2DM in obese patients.