title: Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes.
abstract: OBJECTIVE
  Intensification of insulin therapy in patients with type 2 diabetes, while improving glycemic control, often leads to an increase in body weight and other markers of cardiovascular risk. The effects of pramlintide as an adjunct to basal insulin titration (without mealtime insulin) on glycemia and cardiovascular risk markers were examined.
  
  
  METHODS
  This was a post hoc analysis of a 16-week, double-blind, placebo-controlled study in patients with type 2 diabetes (N = 211) using insulin glargine (without mealtime insulin) +/- oral agents. Patients were randomized to treatment with placebo or pramlintide (60 or 120 mug with major meals), and insulin glargine was titrated to target a fasting plasma glucose concentration of > or = 70 to < 100 mg/dL.
  
  
  METHODS
  Endpoints included the change from baseline to Week 16 in body weight, high sensitivity C-reactive protein (hsCRP), triglycerides, HDL, LDL, and blood pressure.
  
  
  RESULTS
  Pramlintide-treated patients lost weight and placebo-treated patients gained weight during 16 weeks of treatment (-1.6 +/- 0.3 kg vs. +0.7 +/- 0.3 kg, p < 0.001; mean +/- SE). hsCRP was reduced in pramlintide-treated versus placebo-treated patients (-0.8 +/- 0.2 mg/L vs. 0.1 +/- 0.2 mg/L, p < 0.01; mean +/- SE). Patients with baseline hsCRP > 3 mg/L (high cardiovascular risk) demonstrated greater hsCRP reductions with pramlintide versus placebo treatment at Week 16 (p < 0.05). Patients with baseline triglycerides > or = 150 mg/dL or > or = 200 mg/dL (high cardiovascular risk) showed significant reductions from baseline in triglyceride concentrations with pramlintide (-43 +/- 14 mg/dL or -59 +/- 19 mg/dL; p < 0.05; mean +/- SE) but not with placebo (1 +/- 29 mg/dL or -3 +/- 54 mg/dL; mean +/- SE). No significant differences between pramlintide and placebo were observed for changes in HDL, LDL, or blood pressure. Pramlintide treatment was generally well tolerated. The most frequent adverse event related to pramlintide was mild-to-moderate nausea (31% pramlintide vs. 10% placebo). Pramlintide added to basal insulin did not increase the incidence of hypoglycemia. A limitation of the study was its relatively short duration.
  
  
  CONCLUSIONS
  Pramlintide, as an adjunct to basal insulin, was associated with improvements in several cardiovascular risk markers, warranting long-term clinical studies to determine its potential effects on cardiovascular risk.
authors.affiliation: Rockwood Clinic, Spokane, WA, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Wysham
authors.forename: Cameron
authors.initials: C
authors.lastname: Lush
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.forename: Holly
authors.initials: H
authors.lastname: Maier
authors.forename: Ken
authors.initials: K
authors.lastname: Wilhelm
mesh_terms: D000368:Aged; D000682:Amyloid / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D000682:Amyloid; D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D058228:Islet Amyloid Polypeptide; D010919:Placebos; D014280:Triglycerides; D000069036:Insulin Glargine; D002097:C-Reactive Protein; C105254:pramlintide