The effects of LY2189265, a long-acting glucagon-like peptide-1 analogue, in a randomized, placebo-controlled, double-blind study of overweight/obese patients with type 2 diabetes: the EGO study.

AIM: To evaluate the efficacy and tolerability of once-weekly LY2189265 (LY), a novel glucagon-like peptide-1 (GLP-1) IgG4-Fc fusion protein, in patients with type 2 diabetes failing oral antihyperglycaemic medications (OAMs). METHODS: Placebo-controlled, double-blind study in 262 patients (mean age 57 ± 12 years; BMI 33.9 ± 4.1 kg/m(2); and glycosylated haemoglobin A1c (A1c) 8.24 ± 0.93%) receiving two OAMs. Patients were randomized to once-weekly subcutaneous injections of placebo or LY 0.5 mg for 4 weeks, then 1.0 mg for 12 weeks (LY 0.5/1.0); 1.0 mg for 16 weeks (LY 1.0/1.0); or 1.0 mg for 4 weeks, then 2.0 mg for 12 weeks (LY 1.0/2.0). RESULTS: At week 16, A1c changes (least-squares mean ± standard error) were -0.24 ± 0.12, -1.38 ± 0.12, -1.32 ± 0.12 and -1.59 ± 0.12%, in the placebo, LY 0.5/1.0, LY 1.0/1.0 and LY 1.0/2.0 arms, respectively (all p < 0.001 vs. placebo). Both fasting (p < 0.001) and postprandial (p < 0.05) blood glucose decreased significantly compared to placebo at all LY doses. Weight loss was dose dependent and ranged from -1.34 ± 0.39 to -2.55 ± 0.40 kg at 16 weeks (all p < 0.05 vs. placebo). At the highest LY dosage, the most common adverse events were nausea (13.8%), diarrhoea (13.8%) and abdominal distension (13.8%). Hypoglycaemia was uncommon overall (≤0.8 episodes/patient/30 days) but more common with LY than placebo through the initial 4 weeks (p < 0.05). No differences in cardiovascular events or blood pressure were shown between treatments. CONCLUSIONS: LY2189265, given to overweight/obese patients with type 2 diabetes for 16 weeks in combination with OAMs, was relatively well tolerated and significantly reduced A1c, blood glucose and body weight.