Pramlintide reduces postprandial glucose excursions when added to regular insulin or insulin lispro in subjects with type 1 diabetes: a dose-timing study.
OBJECTIVE
To assess the postprandial glucose-lowering effect of the human amylin analog pramlintide when given with either regular insulin or insulin lispro in subjects with type 1 diabetes, with an emphasis on the optimal dose timing relative to meals.


METHODS
In this randomized, single-blind, placebo-controlled, five-way crossover study, 19 subjects with type 1 diabetes using regular insulin and 21 subjects with type 1 diabetes using insulin lispro underwent five consecutive mixed meal tests. In randomized order, subjects received subcutaneous injections of placebo at -15 min or 60 microg pramlintide at -15, 0, +15, or +30 min relative to the meal after an overnight fast. Regular insulin or insulin lispro was injected at -30 and 0 min, respectively, at doses that were adjusted appropriately for both the content of the standardized meal and the anticipated effects of pramlintide. Plasma glucose concentrations were measured before and during the 4-h postmeal period.


RESULTS
In both the regular insulin and insulin lispro groups, pramlintide injections at all four time points lowered the postprandial glucose excursion (36 to >100% reduction in incremental area under the concentration time curve from 0 to 4 h (AUC(0-4 h)) compared with placebo. However, only preprandial injections of pramlintide (-15 and 0 min) were able to prevent the initial postprandial surge in glucose. The optimal time for pramlintide injection was 0 min, which reduced the postprandial glucose excursion by >100% compared with regular insulin plus placebo (incremental AUC(0-4 h): -0.6 +/- 2.5 vs. 11.0 +/- 2.9 mmolx h(-1) x l(-1), P < 0.0007) and by 75% compared with insulin lispro plus placebo (incremental AUC(0-4 h): 2.5 +/- 2.1 vs. 10.0 +/- 2.5 mmol x h(-1) x l(-1), P < 0.0098). No serious adverse events were reported.


CONCLUSIONS
Pramlintide, given at or just before a meal, reduces the postprandial glucose excursion in subjects with type 1 diabetes, regardless of whether added to regular insulin or a rapid-acting insulin analog.
Amylin Pharmaceuticals, Inc, San Diego, California 92121, USA. cweyer@amylin.com
Christian
C
Weyer
Alan
A
Gottlieb
Dennis D
DD
Kim
Karen
K
Lutz
Sherwyn
S
Schwartz
Maria
M
Gutierrez
Yan
Y
Wang
James A
JA
Ruggles
Orville G
OG
Kolterman
David G
DG
Maggs
D000293:Adolescent; D000328:Adult; D000368:Aged; D000682:Amyloid / Q000008:administration & dosage* / Q000009:adverse effects; D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D061268:Insulin Lispro; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D058228:Islet Amyloid Polypeptide; C105254:pramlintide