Pramlintide reduces postprandial glucose excursions when added to insulin lispro in subjects with type 2 diabetes: a dose‐timing study

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Abstract
Background To assess the postprandial glucose‐lowering effect of the human amylin analog pramlintide when given with insulin lispro in subjects with type 2 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 2 diabetes using insulin lispro underwent five consecutive mixed‐meal tests. In randomized order, subjects received subcutaneous injections of placebo at −15 min or 120‐µg pramlintide at −15, 0, +15, or +30 min relative to the standardized breakfast after an overnight fast. Insulin lispro was injected at 0 min 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 When injected at 0 min, pramlintide reduced the postprandial glucose excursion by 81% compared to insulin lispro + placebo (incremental AUC0–4 h (mean ± SE) 2.0 ± 1.5 vs. 10.4 ± 2.2 mmol/h/L, P < 0.05). When pramlintide was injected at −15, +15, and +30 min, the postprandial incremental glucose AUC0–4 h was also significantly reduced (P < 0.05), but to a lesser extent (42 to 73%). Pramlintide treatment was well tolerated and no serious adverse events were reported. Conclusions Administration of pramlintide either at or just prior to a meal caused a greater reduction in postprandial glucose than either administration of placebo or postmeal pramlintide injections in subjects with type 2 diabetes treated with a rapid‐acting insulin analog, insulin lispro. Copyright © 2004 John Wiley & Sons, Ltd.