Exenatide once-weekly (EQW, Bydureon™) injection, a new glucagon-peptide-1 (GLP-1) agonist, was approved in Februrary 2012 for treatment of patients with type 2 diabetes. Its role in diabetes, like other GLP-1 agonists (exenatide twice daily injection, Byetta® and liraglutide once daily injection, Victoza®), is to be added to oral medications for better glycemic control and to help patients lose weight; however when to add a GLP-1 agonist versus other therapies, including long-acting insulin, is not always clear and often patient-dependent. Studies have shown that EQW lowers A1C more than Byetta® and is similar to Victoza®.1 But, how EQW compares to a long-acting insulin, like insulin glargine (IG), in terms of safety and efficacy will help determine its true place in therapy.
Diamant and colleagues compared the safety and efficacy of EQW and IG titrated to glucose targets in patients with type 2 diabetes in the phase 3 trial, titled DURATION-3. The results of the first 26 weeks of the treatment groups were previously reported and found an improvement in glycemic control with EQW.2 The present study is an interim report of the extension of the original trial and includes data for 84 weeks (planned follow-up is at least 2.5 years). The trial is a multi-center, open-label, randomized, two-arm, parallel trial to assess the long-term safety and efficacy of EQW and IG. The efficacy objectives include the change in A1C, time to failure of glycemic control (A1C ≥ 7%), percent of patients achieving A1C <7.0 and ≤6.5%, and changes in body weight, glucose values and lipids. Safety objectives include the incidence of adverse effects and hypoglycemia.3
The extension study included 390 (194 EQW and 196 IG) of the 415 patients who completed the 26-week DURATION-3 trial. Eligible patients had type 2 diabetes and were at least 18 years, had suboptimal glycemic control after maximizing metformin (1500 mg or more) or metformin and sulfonylurea therapy for at least 8 weeks (A1C 7.1-11%), and a BMI of 25-45 with stable body weight for at least 3 months. The mean duration of diabetes was 8 years in the EQW group and 7.8 years in the IG group and mean BMI was 32 kg/m2 in both groups. Patients in the EQW group received a 2 mg injection of exenatide weekly. Patients in the IG group received 10 IU of insulin on day 1, and then were titrated to target using the Initiate Insulin by Aggressive Titration and Education (INITIATE) dosing algorithm.
At 84 weeks, mean A1C decreased from baseline (8.3%) by a mean 1.2±0.1% in the EQW group versus 1.0±1% in the IG group resulting in a treatment difference of -0.18±0.8% favoring EQW (p=0.029). There was no difference between the groups in reached an A1C <7% (EQW 44.6%; IG 36.8%, p=0.084), however more patients achieved an A1C ≤6.5% in the EQW group (31.3% versus 20.2% for IG, p=0.009). The mean time to failure was longer with EQW (57.1±1.9 weeks) compared to IG (47±1.9 weeks, p=0.0007), and IG lowered fasting glucose levels greater than EQW (p=0.003). Patients taking EQW lost 2.1 kg of body weight, whereas those taking IG gained 2.4 kg (p<0.001). Rates of hypoglycemia were significantly greater in the IG group regardless if on a sulfonylurea. Diarrhea and nausea occurred significantly more frequently in the EQW group in the initial 26 weeks and lessened with time; after 26 weeks more patients in the EQW group reported an injection site nodule.3
This study showed that patients treated with EQW continued to experience better glycemic control with sustained overall weight loss and a lower risk of hypoglycemia than patients treated with IG over 84 weeks.3 However, while there were statistical differences in the endpoints, the clinical importance of this improvement in glycemic control is uncertain. Limitations of this study ...