title: Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial.
abstract: OBJECTIVE
  The autoimmune-mediated destruction of pancreatic beta-cells in Type 1 diabetes mellitus renders patients deficient in two glucoregulatory peptide hormones, insulin and amylin. With insulin replacement alone, most patients do not achieve glycaemic goals. We aimed to determine the long-term efficacy and safety of adjunctive therapy with pramlintide, a synthetic human amylin analogue, in patients with Type 1 diabetes.
  
  
  METHODS
  In a double-blind, placebo-controlled, parallel-group, multicentre study, 651 patients with Type 1 diabetes (age 41 +/- 13 years, HbA(1c) 8.9 +/- 1.0%, mean +/- sd) were randomized to mealtime injections of placebo or varying doses of pramlintide, in addition to their insulin therapy, for 52 weeks.
  
  
  RESULTS
  Addition of pramlintide [60 microg three times daily (TID) or four times daily (QID)] to insulin led to significant reductions in HbA(1c) from baseline to Week 52 of 0.29% (P < 0.011) and 0.34% (P < 0.001), respectively, compared with a 0.04% reduction in placebo group. Three times the proportion of pramlintide- than placebo-treated patients achieved an HbA(1c) of < 7%. The greater reduction in HbA(1c) with pramlintide was achieved without an increase in concomitant insulin use and was accompanied by a significant reduction in body weight from baseline to Week 52 of 0.4 kg in the 60 microg TID (P < 0.027) or QID (P < 0.040) pramlintide treatment groups, compared with a 0.8-kg gain in body weight in the placebo group. The most common adverse event in pramlintide-treated patients was transient, mild-to-moderate nausea.
  
  
  CONCLUSIONS
  These results show that mealtime amylin replacement with pramlintide, as an adjunct to insulin therapy, improves long-term glycaemic and weight control in patients with Type 1 diabetes.
authors.affiliation: Medstar Clinical Research, Washington DC, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Ratner
authors.forename: R
authors.initials: R
authors.lastname: Dickey
authors.forename: M
authors.initials: M
authors.lastname: Fineman
authors.forename: D G
authors.initials: DG
authors.lastname: Maggs
authors.forename: L
authors.initials: L
authors.lastname: Shen
authors.forename: S A
authors.initials: SA
authors.lastname: Strobel
authors.forename: C
authors.initials: C
authors.lastname: Weyer
authors.forename: O G
authors.initials: OG
authors.lastname: Kolterman
mesh_terms: D000328:Adult; D000368:Aged; D000682:Amyloid / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; C105254:pramlintide