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ADA: Safety and Efficacy of Once-Monthly Exenatide over 20 Weeks in Patients with Type 2 Diabetes

Exenatide, a GLP-1 receptor agonist, improves glycemic control and body weight with twice daily or once weekly subcutaneous (SC) injections in patients with type 2 diabetes (T2DM)….

A new formulation, exenatide suspension, uses the extended-release microspheres of exenatide once weekly (ExQW) with a triglyceride-based diluent that enables delivery of higher doses with less frequency. The safety and efficacy of 3 monthly doses of exenatide suspension (ExQM; 5, 8, or 11mg SC) or ExQW (2mg) as a reference arm, were assessed in a randomized, open-label, controlled study in 121 patients (36%F, 50±10y, WT 97±19kg, A1C 8.5±1.2%, FPG 185±45mg/dL, diabetes duration 6±5y, mean±SD) with T2DM treated with diet/exercise, metformin (MET), pioglitazone (PIO), or MET+PIO. Across 20wks, patients received 5 monthly ExQM injections or 20 weekly ExQW injections, with high patient retention (94%). Sustained plasma levels were achieved with all ExQM doses.

Greater peak to trough variability was observed with ExQM than ExQW, however mean trough concentrations remained within the therapeutic range with all ExQM doses. The 2 highest ExQM doses achieved levels similar to ExQW. As with ExQW, ExQM approached undetectable levels 8wks after last injection. A1C, FPG, and WT were substantially improved with all doses of ExQM and were comparable to ExQW (Table). Evaluable and ITT results were comparable. No unique safety findings were observed with ExQM relative to ExQW. The most frequent AEs were: ExQM, headache (17-27%) and nausea (17-23%); ExQW, headache (30%) and diarrhea (27%) (ITT). No major or minor hypoglycemia was observed. One AE (vomiting/ExQM) led to withdrawal. There was no evidence of prolonged AE duration with ExQM or ExQW. ExQM was well-tolerated with robust improvements in glycemic control in patients with T2DM, supporting further development of the suspension formulation. [Table]

 
N

Baseline A1C (%)

[Delta]A1C (%)

A1C [lt]7% (Wk20)

[Delta]FPG (mg/dL)

[Delta]WT (kg)

ExQW (2mg)

29
8.6[plusmn]0.2
-1.5[plusmn]0.2
48%
-34[plusmn]9
-1.4[plusmn]0.6

ExQM (5mg)

26
8.4[plusmn]0.2
-1.3[plusmn]0.2
50%
-25[plusmn]8
-1.1[plusmn]0.8

ExQM (8mg)

28
8.6[plusmn]0.2
-1.3[plusmn]0.3
57%
-30[plusmn]10
-0.4[plusmn]0.6

ExQM (11mg)

27
8.4[plusmn]0.3
-1.5[plusmn]0.2
70%
-49[plusmn]9
-1.1[plusmn]0.7

Mean[plusmn]SE [Delta] from baseline to Wk20, Evaluable Population.

 

Author(s):LEIGH MACCONELL, JARET MALLOY, WENYING HUANG, BRENDA CIRINCIONE, LARRY SHEN, LISA PORTER: Scientific Sessions Late Breaking Abstract Sunday, June 26, 2011 Abstract -46-LB