Use of concomitant glucose-lowering therapies and associated treatment results observed in clinical trials of twice-daily exenatide.

OBJECTIVE: To explore, by post hoc analyses of pooled data, the efficacy and safety of the use of exenatide twice daily (BID) in patients stratified by baseline glucose-lowering therapies. METHODS: Patients with type 2 diabetes from long-term randomized controlled trials who were treated with exenatide BID were classified into concomitant medication groups on the basis of background treatment (diet and exercise only, metformin only, sulfonylurea only, thiazolidinedione only, metformin + sulfonylurea, metformin + thiazolidinedione, or insulin with or without other oral antihyperglycemic medications). Seventeen studies were included in the analyses (N = 2,096). RESULTS: In these analyses of patients treated with exenatide BID for 12 to 30 weeks, there were significant decreases from baseline in hemoglobin A(1c) (A1C) and fasting glucose levels in all groups and significant decreases from baseline in body weight in all groups except the thiazolidinedione-only group. The decrease in A1C appeared to be greater in the insulin group than in the other groups, likely because the insulin dose was titrated whereas doses of concomitant antihyperglycemic medications were generally not titrated. Overall, changes in blood pressure and lipids were small. Across all groups, the most common adverse effects were gastrointestinal events. Hypoglycemia was more common in the sulfonylurea-only, metformin + sulfonylurea, and insulin groups than it was in the other concomitant medication groups. CONCLUSION: The use of exenatide BID across a wide range of background therapies was associated with reductions in A1C, fasting glucose, and body weight. Gastrointestinal adverse events were common.