Acute Metabolic Effects of LAF 237 in Type 2 Diabetics
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 3

Summary: 
      Incretin hormones (GIP and GLP-1) stimulate insulin release in a glucose dependant manner,
      hence are necessary for maintenance of normal glucose tolerance. Both GIP and GLP-1 are
      degraded and inactivated by DPP-4.

      LAF 237 is an inhibitor of DPP-4 that has been shown to increase meal-stimulated levels of
      intact GLP-1 in animals and patients with T2DM..

      The purpose of the current study is to explore the acute effects of LAF237 on the rate of
      appearance and disappearance of glucose in type 2 diabetics. Secondary objectives include the
      effect on FPG, insulin secretion rates, glucagon and FFA levels, and rate of glucose entry
      from the GI tract.
    

Detailed description: 
      Study Design Double blind, placebo-controlled, randomized, two -period crossover study.
      Sixteen (16) both sexes diabetic patients will be enrolled and randomized to receive one of
      two treatment sequences (LAF-placebo or placebo-LAF).

      At screening, patients will begin a weight maintaining diet containing 50% carbohydrates, 30%
      protein and 20% fat.

      Within 7 days from screening patients will be scheduled for treatment 1. Patients will begin
      a 10-hour overnight fast on Day -1 at ~21h00. Patients will be admitted to GCRC next day.
      Fasting plasma glucose sample will be drawn and following this the patient will be served a
      standard breakfast containing 1/5 of their caloric allotment (50% carbohydrates, 30% protein
      and 20% fat). At noon patient will be fed a standard lunch containing 2/5 of their caloric
      allotment (50% carbohydrates, 30% protein and 20% fat). At 14h30 (-210) an infusion of 3-3H
      glucose will be started and continued until 08h00 next day (20 µCi x FPG/100 continuous,
      0.20/min). At 17h30 (-30) patients will ingest 100 mg of LAF237 or placebo with 200 ml of
      water. At 18h00 (time zero) patients will be served a dinner (2/5 of their caloric
      allotment). The carbohydrates (glucose) in the meal will be labeled with 75 µCi of
      [1-14C]-glucose.

      At -60, -50, -40, -35, -30, -20, -10, -5, and 0 minutes before dinner plasma samples for
      determination of glucose, insulin, C-peptide, glucagons, GLP-1, GIP, FFA, lactate, and amino
      acid concentrations and 3-3H glucose radioactivity will be drawn. Following dinner, further
      blood samples will be drawn every 15 minutes for 3.5 hours (18h00-21h30) and every 30 minutes
      for the next 10.5 hours (22h00-08h00 Day 2). Post dinner samples will be analyzed for the
      above parameter as well as for 14C glucose radioactivity. At 08h00 on Day 2, both catheters
      will be removed and the patients will be fed breakfast and then released from the site.

      In addition to blood samples, urine from dinner time until 08h00 on Day 2 will be collected.
    

Intervention name(s): LAF 237
Intervention type(s): Drug
Intervention MeSH terms: Vildagliptin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Treatment
Keywords: diabetes; rate of appearance of glucose; insulin secretion; glucagon