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- Title
Pramlintide reduces postprandial glucose excursions when added to regular insulin or insulin lispro in subjects with type 1 diabetes: a dose-timing study.
- Authors
Weyer, Christian; Gottlieb, Alan; Kim, Dennis D.; Lutz, Karen; Schwartz, Sherwyn; Gutierrez, Maria; Wang, Yan; Ruggles, James A.; Kolterman, Orville G.; Maggs, David G.
- Abstract
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. RESEARCH DESIGN AND 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 µg 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[sub 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 rejection was 0 min, which reduced the postprandial glucose excursion by >100% compared with regular insulin plus placebo (incremental AUC[sub 0-4 h]: -0.6 ± 2.5 vs. 11.0 ± 2.9 mmol·h[sup -1] · l[sup -1], P < 0.0007) and by 75% compared with insulin lispro plus placebo (incremental AUC[sub 0-4 h]: 2.5 ± 2.1 vs. 10.0 ± 2.5 mmol · h[sup -1] · l[sup -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.
- Subjects
INSULIN derivatives; AMYLIN; TREATMENT of diabetes
- Publication
Diabetes Care, 2003, Vol 26, Issue 11, p3074
- ISSN
0149-5992
- Publication type
journal article
- DOI
10.2337/diacare.26.11.3074