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

Diabetes Obes Metab. 2011 May;13(5):418-25. doi: 10.1111/j.1463-1326.2011.01366.x. Epub 2011 Jan 19.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptides / analogs & derivatives
  • Glycated Hemoglobin A / drug effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Immunoglobulin Fc Fragments / administration & dosage
  • Immunoglobulin Fc Fragments / adverse effects
  • Immunoglobulin Fc Fragments / therapeutic use*
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / complications*
  • Postprandial Period
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use*
  • Treatment Outcome
  • Weight Loss / drug effects*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • dulaglutide