Does the drug Galvus enhance the effects of a protein preload to reduce blood glucose concentrations after a meal?

22 males with type 2 diabetes, treated with metformin monotherapy, will be studied, each on 4 separate occasions in a randomized, double-blind crossover fashion to evaluate the effects of: (1) A protein preload (25 g chocolate-flavoured whey protein dissolved in 250 mL water (89 kcal)) in combination with placebo (2) A protein preload (25 g chocolate-flavoured whey protein dissolved in 250 mL water (89 kcal)) in combination with vildagliptin (50 mg) (3) A control preload (250 ml water with chocolate flavouring (8 kcal)) in combination with placebo (4) A control preload (250 ml water with chocolate flavouring (8 kcal)) in combination with vildagliptin (50 mg) on blood glucose, insulin, glucagon and total and intact GLP-1 and GIP concentrations, and the gastric emptying of a carbohydrate-containing meal. The study days will be separated by at least 7 days. On the evening before each of the study days (~1900 h), participants will be given a standardised evening meal (McCain’s frozen beef lasagne (McCain Foods Proprietary Ltd); 2472 kJ) to consume with water. With this meal, participants will be instructed to take their usual metformin dose, as well as 50 mg of vildagliptin, or matched placebo. Following this meal, participants will be asked to fast from solids and liquids (other than water) until the following morning. Participants will then attend the Discipline of Medicine at 0830 h on the following morning. On arrival, an intravenous cannula will be inserted into an antecubital vein for blood sampling. Following this (t = -90 min), a baseline blood sample will be taken, then participants will ingest either 50 mg of vildagliptin, or placebo, with 100 ml of water. One hour later (t = -30 min), they will consume a preload drink containing either 25 g chocolate-flavoured whey protein dissolved in 250 mL water (89 kcal), or control (250 ml water with chocolate flavouring (8 kcal)), within 2 minutes. Thirty minutes later (t = 0 min), participants will eat a meal consisting of 65 g powdered potato (Deb, Epping, NSW, Australia) and 20 g glucose, reconstituted with 200 mL water and 1 egg yolk containing 100 microlitres of 13C-octanoic acid. Participants will consume the meal within 5 minutes. Breath samples will be collected immediately before, and every 5 minutes after, meal ingestion in the first hour and every 15 minutes for a further 3 hours for the measurement of gastric emptying. Venous blood samples (~10 mL) will be taken immediately before the preload administration (t = -30 min), and at t = -15, 0, 15, 30, 60, 90, 120, 180 and 240 min for the measurements of blood glucose, insulin, GLP-1 and GIP (total and intact) and glucagon. At t = 240 minutes, the intravenous cannula will be removed, and participants will then be free to leave the laboratory. On each study day, a total of ~110 mL venous blood will be collected. At the same intervals used for blood sampling, appetite and gastrointestinal sensations will be assessed using 100 mm visual analogue scales. Gastric emptying of the carbohydrate meal, labelled with 13C octanoic acid, will be measured by excretion of 13CO2 in the breath by mass spectrometer. This technique has been validated against the “gold-standard” scintigraphy. Half-emptying time (t50) and gastric emptying coefficient (GEC) will be calculated.