A new study published in Diabetes, Obesity & Metabolism evaluated the extent of the glucagon lowering effect by dipeptidyl peptidase (DPP)-4 inhibitors. This was a single-center, randomized, cross-over study wherein 28 metformin-treated patients with type-2 diabetes (T2D) were treated with vildagliptin (50 mg twice daily) or the sodium-glucose co-transporter-2 (SGLT-2) inhibitor, dapagliflozin (10 mg once daily) for two weeks, with a four week wash out period. After each treatment period, a meal test was undertaken with measurements of islet and incretin hormones and their four-hour area under the curve (AUC) levels were estimated. It was observed that the fasting glucagon and postprandial glucagon were approximately 15% lower after vildagliptin compared to the sodium-glucose co-transporter-2 (SGLT-2) inhibitor. In addition, this beneficial effect of vildagliptin led to stronger early (15 min) C-peptide response and higher four-hour AUCC-peptide, higher four-hour AUC of the intact form of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) and lower four-hour AUC of total GIP and GLP-1. Therefore, it was concluded that treatment with DPP-4 inhibition with vildagliptin results in 15% lower fasting and postprandial glucagon levels compared to a SGLT-2 inhibitor. Additionally, DPP-4 inhibition induces a more rapid insulin secretion and higher levels of intact incretin hormones resulting in stronger feedback inhibition of incretin hormone secretion than SGLT-2 inhibition.