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

Diabet Med. 2004 Nov;21(11):1204-12. doi: 10.1111/j.1464-5491.2004.01319.x.


Aims: 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amyloid / adverse effects
  • Amyloid / therapeutic use*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Islet Amyloid Polypeptide
  • Male
  • Middle Aged


  • Amyloid
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Islet Amyloid Polypeptide
  • pramlintide