Incretin mimetic approved as adjunctive therapy in type 2 diabetes mellitus not adequately controlled by a thiazolidinedione
AMYLINIncretin mimetic approved as adjunctive therapy in type 2 diabetes mellitus not adequately controlled by a thiazolidinedione
This synthetic peptide demonstrates incretin mimetic actions, enhancing glucose-dependent insulin secretion by the pancreatic beta-cell, suppressing inappropriately elevated glucagon secretion, and slowing gastric emptying. Exenatide was previously approved as add-on therapy to improve glycemic control in patients with type 2 diabetes mellitus not adequately controlled by metformin and/or a sulfonylurea. On December 28, 2006, FDA approved exenatide as adjunctive therapy to improve glycemic control in patients with type 2 diabetes not adequately controlled by a thiazolidinedione.
Efficacy. The efficacy of exenatide used as add-on therapy with a thiazolidinedione (pioglitazone or rosiglitazone) was evaluated in a 16-week, randomized, double-blind, placebo-controlled trial. Patients with type 2 diabetes who had inadequate glycemic control and were taking a thiazolidinedione with (79%) or without (21%) metformin were randomized to receive exenatide (n=121) or placebo (n=112). The majority (84%) of patients were Caucasian; 8% of patients were Hispanic, and 3% were Black. Baseline hemoglobin A1c (HbA1c) levels were similar between the placebo and exenatide groups (7.9%). Treatment with exenatide was initiated at 5 mcg twice daily for 4 weeks and then increased to 10 mcg twice daily for 12 weeks. Exenatide or placebo was injected subcutaneously before the morning and evening meals. After 16 weeks of treatment, exenatide resulted in statistically significant reductions in HbA1c from baseline (–0.8%) compared with placebo (+0.1%; P<.0001). Additionally, among patients with a baseline HbA1c >7%, a higher proportion of those treated with exenatide achieved HbA1c ≤7% (62.3%) compared with those receiving placebo (16.2%; P<.0001). Patients treated with exenatide also experienced a greater change in body weight from baseline (–1.5 kg) compared with those treated with placebo (–0.2 kg; P<.0001).
Dosing. Exenatide therapy should be initiated as a 5-mcg dose administered twice daily within the 1-hour period before each of the 2 main meals of the day, ≥6 hours apart. Exenatide should not be administered after a meal. The exenatide dose can be increased to 10 mcg twice daily after 1 month of therapy. Doses should be administered as subcutaneous injections in the thigh, abdomen, or upper arm.