HARMONY 4: randomised clinical trial comparing once-weekly albiglutide and insulin glargine in patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea

• Published in: Diabetologia Vol. 57; no. 12; pp. 2475 - 2484
• Main Authors: Weissman, Peter N., Carr, Molly C., Ye, June, Cirkel, Deborah T., Stewart, Murray, Perry, Caroline, Pratley, Richard
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2014; Springer; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blood Glucose; Clinical trials; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Drug Administration Schedule; Drug Therapy, Combination; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting; Female; Glucagon; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide 1 - analogs & derivatives; Glucagon-Like Peptide 1 - therapeutic use; Glucose; Human Physiology; Humans; Hypoglycemia; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Insulin; Insulin Glargine; Insulin, Long-Acting - administration & dosage; Insulin, Long-Acting - therapeutic use; Internal Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metformin - therapeutic use; Middle Aged; Pancreatitis; Patients; Peptides; Retreatment; Sulfonylurea Compounds - therapeutic use; Treatment Outcome; Young Adult; United States > US; Type 2 diabetes; Insulin glargine; Albiglutide; GLP-1 agonist; Endocrinopathy; Human; Pancreatic hormone; Agonist; Metabolic diseases; Insulin; Biguanides; Sulfonylureas; Clinical trial; Metformin
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-014-3360-3

Aims/hypothesis
The aim of this study was to compare the efficacy and safety of once-weekly albiglutide with once-daily insulin glargine (A21Gly,B31Arg,B32Arg human insulin) in patients with type 2 diabetes inadequately controlled on metformin with or without sulfonylurea.
Methods
This was a randomised, open-label, multicentre (
n
 = 222), parallel-group, non-inferiority out-patient clinical trial, with 779 patients enrolled in the study. The study was conducted in 222 centres located in four countries. Patients aged ≥18 years with type 2 diabetes treated with metformin (±sulfonylurea) for at least 3 months with a baseline HbA
1c
7.0–10.0% (53.0–85.8 mmol/mol) were randomly assigned (2:1) via a computer-generated randomisation sequence with a voice response system to receive albiglutide (30 mg once a week,
n
 = 504) or insulin glargine (10 U once a day,
n
 = 241) added to current therapy. Participants and investigators were not masked to treatment assignment. Doses of each medication were adjusted on the basis of the glycaemic response. The primary endpoint was change from baseline in HbA
1c
at week 52.
Results
In the albiglutide group, HbA
1c
declined from 8.28 ± 0.90% (67.0 ± 9.8 mmol/mol) (mean ± SD) at baseline to 7.62 ± 1.12% (59.8 ± 12.2 mmol/mol) at week 52. A similar reduction occurred in the insulin glargine group (8.36 ± 0.95% to 7.55 ± 1.04% [67.9 ± 10.4 to 59.0 ± 11.4 mmol/mol]). The model-adjusted treatment difference of 0.11% (95% CI −0.04%, 0.27%) (1.2 mmol/mol [95% CI −0.4, 3.0 mmol/mol]) indicated non-inferiority of albiglutide to insulin glargine based on the pre-specified non-inferiority margin of 0.3% (3.3 mmol/mol,
p
 = 0.0086). Body weight increased in the insulin glargine group and decreased in the albiglutide group, with a mean treatment difference of −2.61 kg (95% CI −3.20, −2.02;
p
 < 0.0001). Documented symptomatic hypoglycaemia occurred in a higher proportion of patients in the insulin glargine group than in the albiglutide group (27.4% vs 17.5%,
p
 = 0.0377).
Conclusions/interpretation
Albiglutide was non-inferior to insulin glargine at reducing HbA
1c
at week 52, with modest weight loss and less hypoglycaemia. Both drugs were well tolerated. Albiglutide may be considered an alternative to insulin glargine in this patient population.
Trial registration:
ClinicalTrials.gov NCT00838916 (completed)
Funding:
This study was planned and conducted by GlaxoSmithKline.