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.