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.

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 HbA1c 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 HbA1c at week 52.

Results: In the albiglutide group, HbA1c 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 HbA1c 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.