In healthy humans, SGLT1 substrates stimulate GLP-1 and GIP and slow gastric emptying, regardless of whether they are metabolized, whereas the artificial sweetener sucralose does not. Poorly absorbed sweet tastants (TIM), which probably expose a greater length of gut to nutrients, result in delayed GLP-1 secretion but not in delayed GIP release. These observations have the potential to optimize the use of preloads for glycemic control. This trial was registered at www.actr.org.au as ACTRN12611000775910.

OBJECTIVEMacronutrient “preloads” can reduce postprandial glycemia by slowing gastric emptying and stimulating glucagon-like peptide-1 (GLP-1) secretion. An ideal preload would entail minimal additional energy intake and might be optimized by concurrent inhibition of dipeptidyl peptidase-4 (DPP-4). We evaluated the effects of a low-energy d-xylose preload, with or without sitagliptin, on gastric emptying, plasma intact GLP-1 concentrations, and postprandial glycemia in type 2 diabetes.RESEARCH DESIGN AND METHODSTwelve type 2 diabetic patients were studied on four occasions each. After 100 mg sitagliptin (S) or placebo (P) and an overnight fast, patients consumed a preload drink containing either 50 g d-xylose (X) or 80 mg sucralose (control [C]), followed after 40 min by a mashed potato meal labeled with 13C-octanoate. Blood was sampled at intervals. Gastric emptying was determined.RESULTSBoth peak blood glucose and the amplitude of glycemic excursion were lower after PX and SC than PC (P < 0.01 for each) and were lowest after SX (P < 0.05 for each), while overall blood glucose was lower after SX than PC (P < 0.05). The postprandial insulin-to-glucose ratio was attenuated (P < 0.05) and gastric emptying was slower (P < 0.01) after d-xylose, without any effect of sitagliptin. Plasma GLP-1 concentrations were higher after d-xylose than control only before the meal (P < 0.05) but were sustained postprandially when combined with sitagliptin (P < 0.05).CONCLUSIONSIn type 2 diabetes, acute administration of a d-xylose preload reduces postprandial glycemia and enhances the effect of a DPP-4 inhibitor.