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/m2; 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.