title: Pramlintide improved measures of glycemic control and body weight in patients with type 1 diabetes mellitus undergoing continuous subcutaneous insulin infusion therapy.
abstract: OBJECTIVE
  To assess the safety and efficacy of the addition of pramlintide to continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus (T1DM).
  
  
  METHODS
  We conducted a post hoc analysis of 2 studies: a 29-week, multicenter, randomized, double-blind, placebo-controlled trial (referred to as RCT) (pramlintide, n = 82; placebo, n = 73) and an open-ended, multicenter, open-label, single-arm, observational study (referred to as clinical practice trial) (n = 150), which assessed the addition of pramlintide to CSII therapy in patients with T1DM. Pramlintide was initiated at 15 μg and titrated to 30 or 60 μg with major meals. The mealtime insulin dose was reduced by 30% to 50% at initiation, and then adjusted to optimize glycemic control. Endpoints at 29 weeks (RCT) and 6 months (clinical practice trial) included change in glycated hemoglobin (HbA1c) level, insulin dose, body weight, pre- and postprandial blood glucose level, and tolerability and safety.
  
  
  RESULTS
  In both studies, mean baseline age was approximately 42 years, duration of diabetes was 20 to 24 years, and HbA1c level was approximately 8%. Pramlintide reduced blood glucose excursions and improved the percentage of recorded postprandial blood glucose levels < 180 mg/dL. Mean (± standard deviation) reduction in HbA1c level in the clinical practice trial was -0.3% ± 0.1% (P < 0.0001), and in the RCT was similar between pramlintide- and placebo-treated patients (-0.4% ± 0.1% and -0.3% ± 0.1%, respectively). Glycemic improvements were accomplished, with reductions in mealtime insulin doses (RCT: pramlintide, -23.8% ± 5.2%; placebo, -3.2% ± 4.1%; P < 0.0005; clinical practice trial: -27.5% ± 2.9%; P < 0.0001) and body weight (RCT: pramlintide, -2.2 kg ± 0.5 kg; placebo, +1.4 kg ± 0.3 kg; P < 0.0001; clinical practice trial: -3.2 kg ± 0.4 kg; P < 0.0001). Short-lived nausea, primarily mild to moderate in intensity, was the most common adverse event associated with pramlintide therapy. Severe hypoglycemic events occurred at a rate of 0.56 and 0.34 events per patient-year in pramlintide- and placebo-treated patients, respectively, in the RCT, and at a rate of 0.12 events per patient-year in the clinical practice trial.
  
  
  CONCLUSIONS
  Addition of pramlintide to CSII therapy was safe and effective in patients with T1DM. Pramlintide should be considered for patients who are not able to optimize glycemic control with CSII therapy alone, particularly those with difficulty controlling postprandial blood glucose levels and/or body weight.
  
  
  BACKGROUND
  www.ClinicalTrials.gov identifiers: NCT00042458, NCT00108004.
authors.affiliation: Amylin Pharmaceuticals, LLC, San Diego, CA 92121, USA. kathrin.herrmann@bms.com
authors.forename: Kathrin
authors.initials: K
authors.lastname: Herrmann
authors.forename: Juan P
authors.initials: JP
authors.lastname: Frias
authors.forename: Steven V
authors.initials: SV
authors.lastname: Edelman
authors.forename: Karen
authors.initials: K
authors.lastname: Lutz
authors.forename: Kevin
authors.initials: K
authors.lastname: Shan
authors.forename: Steven
authors.initials: S
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Maggs
authors.forename: Orville G
authors.initials: OG
authors.lastname: Kolterman
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055104:Infusions, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D058228:Islet Amyloid Polypeptide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; C517652:hemoglobin A1c protein, human; C105254:pramlintide