Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonist albiglutide (HARMONY 1 trial): 52-week primary endpoint results from a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes mellitus not controlled on pioglitazone, with or without metformin

Diabetes Obes Metab. 2014 Dec;16(12):1257-64. doi: 10.1111/dom.12382. Epub 2014 Oct 6.

Abstract

Aims: To show that albiglutide, a glucagon-like peptide-1 receptor agonist, is an effective and generally safe treatment to improve glycaemic control in patients with type 2 diabetes mellitus whose hyperglycaemia is inadequately controlled with pioglitazone (with or without metformin).

Methods: In this 3-year, randomized, double-blind, placebo-controlled study, 310 adult patients on a regimen of pioglitazone (with or without metformin) were randomly assigned to receive additional treatment with albiglutide [30 mg subcutaneous (s.c.) once weekly, n = 155] or matching placebo (n = 155). The primary efficacy endpoint was change from baseline to week 52 (intention-to-treat) in glycated haemoglobin (HbA1c).

Results: The model-adjusted change from baseline in HbA1c at week 52 was significantly better with albiglutide than with placebo (-0.8%, 95% confidence interval -1.0, -0.6; p < 0.0001). Change from baseline fasting plasma glucose was -1.3 mmol/l in the albiglutide group and +0.4 mmol/l in the placebo group (p < 0.0001); a significantly higher percentage of patients reached the HbA1c goals with albiglutide (p < 0.0001), and the rate of hyperglycaemia rescue up to week 52 for albiglutide was 24.4 versus 47.7% for placebo (p < 0.0001). Albiglutide plus pioglitazone had no impact on weight, and severe hypoglycaemia was observed rarely (n = 2). With few exceptions, the results of safety assessments were similar between the groups, and most adverse events (AEs) were mild or moderate. The 52-week incidence rates for gastrointestinal AEs for albiglutide and placebo were: 31.3 and 29.8%, respectively (diarrhoea: 11.3 and 8.6%; nausea: 10.7 and 11.3%; vomiting: 4.0 and 4.0%).

Conclusions: Albiglutide 30 mg administered once weekly as an add-on to pioglitazone (with or without metformin) provided effective and durable glucose lowering and was generally well tolerated.

Keywords: albiglutide; glucagon-like peptide-1 agonist; incretins; type 2 diabetes.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / therapeutic use
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / prevention & control*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Incretins
  • Male
  • Metformin / administration & dosage
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Middle Aged
  • Pioglitazone
  • Thiazolidinediones / administration & dosage
  • Treatment Outcome

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Incretins
  • Thiazolidinediones
  • rGLP-1 protein
  • Glucagon-Like Peptide 1
  • Metformin
  • Pioglitazone