Patients with uncontrolled type 2 diabetes display greater reductions in HbA_1c using a regimen of a once-weekly autoinjection of exenatide as compared with twice-daily injections of exenatide. The results of the randomized, double-blind Efficacy and Safety of Exenatide Once Weekly Suspension in Subjects With Type 2 Diabetes study [DURATION-NEO-1; NCT01652716] were presented by Carol H. Wysham, MD, Rockwood Clinic, Spokane, Washington, USA.

A once-weekly administration of the glucagon-like peptide-1 receptor agonist exenatide provides glycemic control and helps with weight loss in individuals with type 2 diabetes [Russell-Jones D et al. Diabetes Care 2012; Blevins T et al. J Clin Endocrinol Metab 2011; Bergenstal RM et al. Lancet 2010; Diamant M et al. Lancet 2010; Drucker DJ et al. Lancet 2008]. However, the current need for reconstitution of the formulation has hindered its use. The present study evaluated a new formulation that does not require reconstitution and that can be administered by a single-use autoinjection pen.

The study involved 377 patients with type 2 diabetes. Other inclusion criteria were attempted control of diabetes using diet and exercise; the use of ≤ 2 of metformin, sulfonylurea, or thiazolidinediones; HbA_1c of 7.1% to 11.0%; body mass index ≤ 45 kg/m²; and fasting plasma glucose < 280 mg/dL. The patients were randomized to receive a once-weekly autoinjection of exenatide 2 mg (n = 229) or conventional twice-daily exenatide 10 µg (n = 148). The modified intention-to-treat population was 229 and 146, respectively. The primary end point was the change in HbA_1c after 28 weeks of treatment in the two study arms (197 and 118 subjects completed, respectively). The demographics and baseline characteristics were similar in both study arms (Table 1).

The change in HbA_1c over time for both study arms featured a similar sharp decline at Week 8, followed by divergent but stabilized levels thereafter. The primary outcome (change in HbA_1c between baseline and Week 28) significantly favored the once-weekly arm (−1.4%) compared with the twice-daily arm (−1.0%; p = .007). The proportion of subjects in the once-weekly exenatide and twice-daily exenatide arms who achieved HbA_1c reduction < 7.0% were similar (49% and 43%, respectively; p = .23), but those who achieved a ≤ 6.5% reduction favored the once-weekly injection regimen (36% and 26%, respectively; p = .05). The decline in fasting plasma glucose was greater for the once-weekly arm from Weeks 6 to 24, but was not significant at Week 28 (−33 mg/dL vs −23 mg/dL for the twice-daily arm; p = .17). The change in postprandial glucose was similar between the study arms, as was the change in body weight (−1.5 ± 0.3 kg for once-weekly exenatide vs −1.9 ± 0.4 kg for twice-daily exenatide).

The prevalence of adverse events (AEs) was overall similar between the study arms (Table 2). However, the prevalence of nausea and diarrhea was lower but the presence of an injection-site nodule was far more common in the once-weekly exenatide arm as compared with the twice-daily arm.

The present results were similar to those of the previous DURATION-5 study [Blevins T et al. J Clin Endocrinol Metab 2011]. This featured administration of exenatide QW, which required reconstitution and administration with a syringe. The researchers concluded that a weekly autoinjection of exenatide that does not require reconstitution provides statistically superior reduction in HbA_1c and fewer gastrointestinal AEs than the regimen of exenatide given by twice-daily injection.