Feed-Back Suppression of Meal-Induced Glucagon-like Peptide 1 (GLP-1) Secretion
Condition: Type 2 Diabetes
Study type: Interventional
Phase: Phase 1

Summary: 
      The present study is a phase I, single-centre, double-blind, randomized, cross-over (3
      treatments, 3 treatment periods and 6 sequences), stratified (background medication:
      metformin vs. diet-only), placebo-controlled study, comparing periods lasting 6-9 days on
      treatment with repeated doses of vildagliptin, sitagliptin, or placebo, with wash-out periods
      between treatment periods lasting 21 days minimum.

      The study was designed to directly compare the effects of vildagliptin and sitagliptin on
      incretin hormone responses, glycaemia, and insulin as well as glucagon secretory responses in
      patients with type 2 diabetes.
    

Detailed description: 
      Design. The present study is a phase I, single-centre, double-blind, randomized, cross-over
      (3 treatments, 3 treatment periods and 6 sequences), stratified (background medication:
      metformin vs. diet-only), placebo-controlled study, comparing periods lasting 6-9 days on
      treatment with repeated doses of vildagliptin, sitagliptin, or placebo, with wash-out periods
      between treatment periods lasting 21 days minimum.

      Experimental procedures. Meal tests were performed in the morning after an overnight fast.
      The standardized mixed meal was composed of 2 eggs (100 g), 1 slice (50 g) of whole grain rye
      bread, 1 slice (50 g) of rye flour bread, 10 g of fat-reduced margarine, 20 g of boiled ham,
      and 25 g of diet jam, amounting to 450 kcal, 50 % carbohydrate, 20 % protein, and 30 % fat
      (based on calorie count). Patients were allowed to drink tea (black or fruit-based) or
      de-caffeinated coffee ad libitum.

      Blood sampling. Plasma glucose was determined in capillary samples taken from hyperaemic ear
      lobes. Venous blood was collected from indwelling venous cannulas placed in a distal forearm
      vein, for the determination of insulin, C-peptide, glucagon, GLP-1 (total), GLP-1 (intact),
      glucose-dependent insulinotropic polypeptide (GIP) (total), GIP (intact), and free fatty
      acids. After drawing basal blood specimens at -15 and 0 min, blood was taken at 15, 30, 45,
      60, 90, 120, 180, and 240 min.

      Laboratory determinations. Glucose, insulin, C-peptide, total GLP-1 (C-terminally directed
      assay), intact GLP-1 (sandwich ELISA), total GIP (C-terminally directed assay), intact GIP
      (N-terminally directed assay) and glucagon were determined.
    

Intervention name(s): Mixed meal test; Vildagliptin; Sitagliptin; Placebo; Metformin; Diet and exercise
Intervention type(s): Other; Drug; Drug; Drug; Drug; Other
Intervention description(s): Mixed meal test were performed in the morning after an overnight fast. The standardized mixed meal was composed of 2 eggs (100 g), 1 slice (50 g) of whole grain rye bread, 1 slice (50 g) of rye flour bread, 10 g of fat-reduced margarine, 20 g of boiled ham, and 25 g of diet jam, amounting to 450 kcal, 50 % carbohydrate, 20 % protein, and 30 % fat (based on calorie count). Patients were allowed to drink tea (black or fruit-based) or de-caffeinated coffee ad libitum.; Vildagliptin (50 mg per tablet) was administered orally twice daily (15 minutes prior to breakfast or test meal, on the last day of treatment period) and without a defined temporal relation to dinner in the evening, irrespective of the stratum defined by the background diabetes treatment.; The dosage of sitagliptin depended on the stratum defined by the background diabetes medication. In patients treated with diet and exercise (no other glucose-.lowering medication), sitagliptin was given as one 100 mg in the morning (15 minutes prior to breakfast or the test meal, on the last day of the treatment period), and a corresponding placebo tablet was administered in the evening (no temporal relation to dinner required).; Placebo was administered orally twice daily: 15 minutes prior to breakfast or the test meal on the last day of treatment period) and one dose in the evening (no temporal relation to dinner required).; For patients continuing with pre-existing metformin treatment, 1000 mg film coated tablets from commercial sources. In half of the patients (stratum: metformin as background medication), metformin was administered orally twice daily at 1000 mg of active compound during of after breakfast and dinner.; Patients treated their diabetes mellitus type 2 with diet/exercise only
Intervention MeSH terms: Metformin; Sitagliptin Phosphate; Vildagliptin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment