Efficacy and Safety of Multiple Doses of Exenatide Once-Monthly Suspension in Patients With Type 2 Diabetes: A Phase II Randomized Clinical Trial

Carol H. Wysham, Leigh MacConell, Elise Hardy
2016 Diabetes Care  
OBJECTIVE This study investigated the efficacy and safety of multiple exenatide oncemonthly suspension (QMS) doses of exenatide-containing microspheres in Miglyol referenced against the clinical dose of exenatide once-weekly (QW) microspheres in aqueous solution. RESEARCH DESIGN AND METHODS In this phase II, randomized, controlled, single-blind study, 121 adults (∼30/arm) with type 2 diabetes and HbA 1c 7.1-11.0% (54-97 mmol/mol) were randomized 1:1:1:1 to subcutaneous exenatide QW 2 mg
more » ... ide QW 2 mg (self-administered) or exenatide QMS 5, 8, or 11 mg (caregiver-administered) for 20 weeks. The primary end point was change in HbA 1c . RESULTS At baseline, mean age was 50 years, HbA 1c was 8.5% (69 mmol/mol), fasting plasma glucose (FPG) was 184 mg/dL, and body weight was 98 kg. At week 20, mean 6 SD HbA 1c reductions were 21.54% 6 1.26% with exenatide QW and 21.29% 6 1.07%, 21.31% 6 1.66%, and 21.45% 6 0.93% with exenatide QMS 5, 8, and 11 mg, respectively (evaluable population: n = 110). There were no significant differences in HbA 1c reductions among the exenatide QMS doses. FPG reductions were 234 6 48 mg/dL with exenatide QW and 225 6 43, 230 6 52, and 249 6 49 mg/dL with exenatide QMS 5, 8, and 11 mg, respectively. Weight decreased with all treatments. For exenatide QMS, nausea (16.7-23.3%) and headache (16.7-26.7%) were the most common adverse events. No major or minor hypoglycemia occurred. CONCLUSIONS All doses of exenatide QMS resulted in efficacy and tolerability profiles consistent with exenatide QW. These results combined with pharmacokinetic and pharmacodynamic modeling could inform dose selection for further development. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are recommended as add-on therapy for patients with type 2 diabetes after failure of oral glucose-lowering medications (1,2). GLP-1RAs target multiple pathophysiologic mechanisms, including stimulating glucose-dependent insulin secretion from pancreatic b-cells, suppressing glucose-dependent glucagon secretion from pancreatic a-cells, slowing gastric motility
doi:10.2337/dc16-0238 pmid:27436275 fatcat:42gojg75djgh5proycri6foota