An additional mechanism of action of pramlintide is control of the rate of gastric emptying. Gastric emptying may be accelerated in patients with diabetes (23-25); furthermore, early postprandial plasma glucose increases in direct proportion to the rate of gastric emptying (26). In studies utilizing both solid and liquid meals, pramlintide prolonged the half-gastric emptying time by 60 to 90 minutes, without any carry-over effect to the subsequent meal (27,28).
A third mechanism of action involves a satiogenic effect, resulting in reduced food intake. In a placebo-controlled, crossover study of patients with type 2 diabetes, pramlintide administration (120 pg) 1 hour before an ad libitum buffet meal resulted in a reduction in caloric intake of approximately 23% compared with placebo (29). Reduction in food intake was independent of nausea, which can accompany pramlintide treatment. This satiogenic effect may help explain the weight loss observed in the long-term clinical trials (30,31).
Short-Term Clinical Studies Assessing Postprandial Glucose Control
Given pramlintide's mechanisms of action which collectively reduce the appearance of glucose into the circulation during the postprandial period, one of its most important effects is a reduction of postprandial glucose concentrations and daily glucose fluctuations. These effects have been examined in several clinical trials in patients with type 2 diabetes treated with mealtime insulin (32,33). In patients using insulin lispro, pramlintide administered immediately prior to a standardized meal significantly reduced postprandial glucose excursions compared with mealtime insulin therapy alone (Fig. 4) (33). Pramlintide achieved this effect with an average reduction in mealtime insulin of approximately 17% (33).
Long-Term, Placebo-Controlled Clinical Studies
Long-term (26-52 weeks), placebo-controlled clinical studies designed to assess the safety and efficacy of pramlintide as an adjunct to mealtime insulin in patients with type 2 diabetes consistently demonstrated improvements in glycemic control with reduction in body weight. Adjunctive pramlintide therapy (120 pg) significantly reduced A1c by —0.6% (vs. —0.2% for placebo, P < 0.05), and did so despite a reduction in daily insulin (Fig. 5) (30,31).
Weight gain is associated with most traditional antihyperglycemic therapies (34). In contrast, the improvement in glycemic control in pramlintide-treated patients was associated with a significant (P < 0.0001) and sustained (P < 0.0001) reduction in body weight. Following
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Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...