title: Pramlintide reduces postprandial glucose excursions when added to insulin lispro in subjects with type 2 diabetes: a dose-timing study.
abstract: BACKGROUND
  To assess the postprandial glucose-lowering effect of the human amylin analog pramlintide when given with insulin lispro in subjects with type 2 diabetes, with an emphasis on the optimal dose timing relative to meals.
  
  
  METHODS
  In this randomized, single-blind, placebo-controlled, five-way crossover study, 19 subjects with type 2 diabetes using insulin lispro underwent five consecutive mixed-meal tests. In randomized order, subjects received subcutaneous injections of placebo at -15 min or 120-microg pramlintide at -15, 0, +15, or +30 min relative to the standardized breakfast after an overnight fast. Insulin lispro was injected at 0 min at doses that were adjusted appropriately for both the content of the standardized meal and the anticipated effects of pramlintide. Plasma glucose concentrations were measured before and during the 4-h postmeal period.
  
  
  RESULTS
  When injected at 0 min, pramlintide reduced the postprandial glucose excursion by 81% compared to insulin lispro + placebo (incremental AUC(0-4 h) (mean +/- SE) 2.0 +/- 1.5 vs. 10.4 +/- 2.2 mmol/h/L, P<0.05). When pramlintide was injected at -15, +15, and +30 min, the postprandial incremental glucose AUC(0-4 h) was also significantly reduced (P<0.05), but to a lesser extent (42 to 73%). Pramlintide treatment was well tolerated and no serious adverse events were reported.
  
  
  CONCLUSIONS
  Administration of pramlintide either at or just prior to a meal caused a greater reduction in postprandial glucose than either administration of placebo or postmeal pramlintide injections in subjects with type 2 diabetes treated with a rapid-acting insulin analog, insulin lispro.
authors.affiliation: Amylin Pharmaceuticals, Inc, San Diego, California 92121, USA. dmaggs@amylin.com
authors.forename: David G
authors.initials: DG
authors.lastname: Maggs
authors.forename: Mark
authors.initials: M
authors.lastname: Fineman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kornstein
authors.forename: Terrie
authors.initials: T
authors.lastname: Burrell
authors.forename: Sherwyn
authors.initials: S
authors.lastname: Schwartz
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: James A
authors.initials: JA
authors.lastname: Ruggles
authors.forename: Orville G
authors.initials: OG
authors.lastname: Kolterman
authors.forename: Christian
authors.initials: C
authors.lastname: Weyer
mesh_terms: D000328:Adult; D000368:Aged; D000682:Amyloid / Q000627:therapeutic use*; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D018592:Cross-Over Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D061268:Insulin Lispro; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D009765:Obesity; D010919:Placebos; D019518:Postprandial Period; D016037:Single-Blind Method
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D058228:Islet Amyloid Polypeptide; D010919:Placebos; C105254:pramlintide