Pramlintide reduces postprandial glucose excursions when added to insulin lispro in subjects with type 2 diabetes: a dose-timing study

Diabetes Metab Res Rev. Jan-Feb 2004;20(1):55-60. doi: 10.1002/dmrr.419.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amyloid / therapeutic use*
  • Area Under Curve
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Body Mass Index
  • Cross-Over Studies
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / analogs & derivatives*
  • Insulin / therapeutic use*
  • Insulin Lispro
  • Islet Amyloid Polypeptide
  • Male
  • Middle Aged
  • Obesity
  • Placebos
  • Postprandial Period
  • Single-Blind Method


  • Amyloid
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Insulin Lispro
  • Islet Amyloid Polypeptide
  • Placebos
  • pramlintide