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Objective: Tachyphylaxis for slowing of gastric emptying is seen with continuous exposure to glucagon-like peptide 1 (GLP-1). We therefore aimed to establish whether prolonged use of a "short-acting" GLP-1 receptor agonist, lixisenatide, achieves sustained slowing of gastric emptying and reduction in postprandial glycemia., Research Design and Methods: A total of 30 patients with metformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) after a 75-g glucose drink, before and after 8 weeks' treatment with lixisenatide (20 μg subcutaneously daily) or placebo, in a double-blind randomized parallel design., Results: Gastric retention of the glucose drink was markedly increased after lixisenatide versus placebo (ratio of adjusted geometric means for area under the curve [AUC] over 240 min of 2.19 [95% CI 1.82, 2.64], P < 0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose ( P < 0.001) and incremental AUC for blood glucose ( P < 0.001). Lixisenatide suppressed both glucagon ( P = 0.003) and insulin ( P = 0.032), but not endogenous glucose production, over 120 min after oral glucose intake. Postprandial glucose lowering over 240 min was strongly related to the magnitude of slowing of gastric emptying by lixisenatide ( r = -0.74, P = 0.002) and to the baseline rate of emptying ( r = 0.52, P = 0.048) but unrelated to β-cell function (assessed by β-cell glucose sensitivity)., Conclusions: Eight weeks' treatment with lixisenatide is associated with sustained slowing of gastric emptying and marked reductions in postprandial glycemia and appearance of ingested glucose. Short-acting GLP-1 receptor agonists therefore potentially represent an effective long-term therapy for specifically targeting postprandial glucose excursions., (© 2020 by the American Diabetes Association.)

Objective: To evaluate effects of vildagliptin and metformin on blood pressure (BP) and heart rate (HR) responses to intraduodenal (ID) glucose in diet-controlled type 2 diabetes., Research Design and Methods: Study A compared vildagliptin (50 mg) and placebo, given 60 min before a 120-min ID glucose infusion at 2 or 4 kcal/min (ID2 or ID4) in 16 patients. Study B compared metformin (850 mg) and placebo, given 30 min before ID2 over 120 min in 9 patients., Results: Systolic ( P = 0.002) and diastolic ( P < 0.001) BP were lower and HR greater ( P = 0.005) after vildagliptin compared with placebo, without interaction between vildagliptin and the glucose infusion rate. In contrast, HR was greater after metformin than placebo ( P < 0.001), without any difference in systolic or diastolic BP., Conclusions: Vildagliptin reduces BP and increases HR, whereas metformin increases HR without affecting BP during ID glucose infusion in type 2 diabetes. These distinct cardiovascular profiles during enteral nutrient exposure may have implications for postprandial hypotension., (© 2017 by the American Diabetes Association.)

Objective: Nutrient "preloads" given before meals can attenuate postprandial glycemic excursions, at least partly by slowing gastric emptying and stimulating secretion of the incretins (i.e., glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]). This study was designed to evaluate whether a protein preload could improve the efficacy of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin to increase incretin concentrations, slow gastric emptying, and lower postprandial glycemia in type 2 diabetes., Research Design and Methods: Twenty-two patients with type 2 diabetes treated with metformin were studied on four occasions, receiving either 50 mg vildagliptin (VILD) or placebo (PLBO) on both the evening before and the morning of each study day. The latter dose was followed after 60 min by a preload drink containing either 25 g whey protein (WHEY) or control flavoring (CTRL), and after another 30 min by a (13)C-octanoate-labeled mashed potato meal. Plasma glucose and hormones, and gastric emptying, were evaluated., Results: Compared with PLBO/CTRL, PLBO/WHEY reduced postprandial peak glycemia, increased plasma insulin, glucagon, and incretin hormones (total and intact), and slowed gastric emptying, whereas VILD/CTRL reduced both the peak and area under the curve for glucose, increased plasma intact incretins, and slowed gastric emptying but suppressed plasma glucagon and total incretins (P < 0.05 each). Compared with both PLBO/WHEY and VILD/CTRL, VILD/WHEY was associated with higher plasma intact GLP-1 and GIP, slower gastric emptying, and lower postprandial glycemia (P < 0.05 each)., Conclusions: In metformin-treated type 2 diabetes, a protein preload has the capacity to enhance the efficacy of vildagliptin to slow gastric emptying, increase plasma intact incretins, and reduce postprandial glycemia., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: Macronutrient "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 Methods: Twelve 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 (13)C-octanoate. Blood was sampled at intervals. Gastric emptying was determined., Results: Both 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)., Conclusions: In type 2 diabetes, acute administration of a D-xylose preload reduces postprandial glycemia and enhances the effect of a DPP-4 inhibitor.