Cardiovascular safety assessment of pramlintide in type 2 diabetes: results from a pooled analysis of five clinical trials.

Background: This report evaluated the cardiovascular safety of the amylin analog pramlintide-an existing diabetes injectable treatment-by comparing relevant cardiovascular adverse events (AEs) reported in previous phase 3 and 4 clinical trials among patients receiving pramlintide and those receiving control treatments.

Methods: Cardiovascular safety of pramlintide was assessed using accepted regulatory medical definitions of AEs reported in five randomized, controlled phase 3 and 4 trials of 16-52 weeks' duration in adults with type 2 diabetes. The original trials compared pramlintide (90-120 mcg twice daily or 30-150 mcg three times daily) with placebo (four studies) or a mealtime rapid-acting insulin analog (one study). Background therapies included insulin alone or in combination with oral glucose-lowering agents. AE data obtained from clinical study reports were combined into one database and analyzed for the intention-to-treat population of 2016 patients (pramlintide,  = 1434; pooled comparator,  = 582). The primary analysis compared reported major adverse cardiovascular events (MACE) between pramlintide and control.

Results: The incidence of reported MACE was similar between pramlintide (4.7 %) and pooled comparators (4.5 %). Secondary analyses included MACE relative risk and hazard ratio point estimates, which ranged from 0.86 to 0.93 for pramlintide relative to comparator treatment; the upper limit of the two-sided 95 % confidence interval did not exceed the threshold of 1.8.

Conclusions: Both the point estimate of the reported MACE frequency and estimated risk ratios showed that mealtime pramlintide as an adjunct to insulin conferred no increased risk of cardiovascular AEs in patients with type 2 diabetes using insulin.