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. 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 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.

Adjunctive therapy with the amylin analogue pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with type 2 diabetes.

The objective of this study was to assess the effect of mealtime amylin replacement with pramlintide on long-term glycemic and weight control in subjects with type 2 diabetes. This 52-week, randomized, placebo-controlled, multicenter, double-blind, dose-ranging study in 538 insulin-treated subjects with type 2 diabetes compared the efficacy and safety of 30-, 75-, or 150-microg doses of pramlintide, a synthetic analogue of the beta-cell hormone amylin, to placebo when injected subcutaneously three times daily (TID) with major meals. Pramlintide therapy led to a mean reduction in HbA1c of 0.9% and 1.0% from baseline to week 13 in the 75- and 150-microg dose groups, which was significant compared to placebo (p = 0.0004 and p = 0.0002, respectively). In the 150-microg dose group, there was a mean reduction in HbA1c of 0.6% from baseline to week 52 (p = 0.0068 compared to placebo). The greater reduction in HbA1c with pramlintide was achieved without increases in insulin use or severe hypoglycemia, and was accompanied by a significant (p < 0.05) reduction in body weight in all dose groups compared to placebo. Three times the proportion of subjects in the 150-microg pramlintide group compared to the placebo group achieved a concomitant reduction in both HbA1c and body weight from baseline to week 52 (48% versus 16%). The most common adverse event reported with pramlintide treatment was nausea, which was mild to moderate and dissipated early in treatment. The results from this study support the safety and efficacy of pramlintide administered three times a day with major meals, in conjunction with insulin therapy, for improving long-term glycemic and weight control in subjects with type 2 diabetes.