title: Fixed ratio dosing of pramlintide with regular insulin before a standard meal in patients with type 1 diabetes.
abstract: Amylin is co-secreted with insulin and is therefore lacking in patients with type 1 diabetes. Replacement with fixed ratio co-administration of insulin and the amylin analogue pramlintide may be superior to separate dosing. This concept was evaluated in a ratio-finding study. Patients with type 1 diabetes were enrolled in a randomized, single-masked, standard breakfast crossover study using regular human insulin injected simultaneously with pramlintide 6, 9 or 12 mcg/unit insulin or placebo. Insulin dosage was reduced by 30% from patients' usual estimates. Plasma glucose, glucagon and pramlintide and adverse events were assessed. All ratios reduced 0-3-h glucose and glucagon increments by >50%. No hypoglycaemia occurred. Adverse events were infrequent and generally mild. All pramlintide/insulin ratios markedly and safely reduced glycaemic excursions and suppressed glucagon secretion in the immediate postprandial state. Further study using one of these ratios to explore the efficacy and safety of longer-term meal-time and basal hormone replacement is warranted.
authors.affiliation: Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Riddle
authors.affiliation: Swedish Pituitary Center, Seattle, WA, USA.
authors.forename: K C J
authors.initials: KC
authors.lastname: Yuen
authors.affiliation: AstraZeneca, Gaithersburg, MD, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: de Bruin
authors.affiliation: AstraZeneca, San Diego, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Herrmann
authors.affiliation: AstraZeneca, Gaithersburg, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: AstraZeneca, Gaithersburg, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Öhman
authors.affiliation: Consultant, La Jolla, CA, USA.
authors.forename: O G
authors.initials: OG
authors.lastname: Kolterman
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D058228:Islet Amyloid Polypeptide / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D062407:Meals; D008875:Middle Aged; D019518:Postprandial Period; D016037:Single-Blind Method
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D005934:Glucagon; C105254:pramlintide
keywords: amylin; pramlintide; type 1 diabetes