Efficacy and tolerability of albiglutide versus placebo or pioglitazone over 1 year in people with type 2 diabetes currently taking metformin and glimepiride: HARMONY 5

AimsTo investigate the efficacy and tolerability of albiglutide, a weekly glucagon-like peptide-1 receptor agonist, when added to metformin and glimepiride in a triple therapy regimen in people with type 2 diabetes mellitus. MethodsThis was a 156-week, randomized, double-blind, parallel-group, multicentre study. In the present paper we describe the primary results, namely those at 52weeks. Adult participants (n=685) were randomly assigned to albiglutide (30mg/week), pioglitazone (30mg/day) or placebo. If needed, blinded uptitration of albiglutide (to 50mg/week) and pioglitazone (to 45mg/day) was allowed. The participant's current dose of metformin (>1500mg/day) was maintained throughout. The glimepiride dose (4mg/day), standardized before randomization, could be decreased if persistent hypoglycaemia occurred. ResultsThe week 52 model-adjusted difference in change of glycated haemoglobin (primary endpoint) for albiglutide versus placebo was -0.87 [95% confidence interval (CI) -1.07, -0.68]%-units (p<0.001), and for albiglutide versus pioglitazone it was 0.25 (95% CI 0.10, 0.40)%-units; therefore, not non-inferior. In the albiglutide group only, fasting plasma glucose reduced rapidly in the first 2weeks. Confirmed hypoglycaemia occurred in 14% of participants on albiglutide, 25% on pioglitazone and 14% on placebo. The mean ( standard error) weight change was -0.42 (+/- 0.2)kg with albiglutide, +4.4 (+/- 0.2)kg (p<0.001) with pioglitazone, and -0.40 (+/- 0.4)kg with placebo and serious adverse events occurred in 6.3, 9.0 and 6.1% of participants in the respective groups. Injection site reactions occurred in 13% of participants on albiglutide and resulted in treatment discontinuation for four participants (1.4%). ConclusionsAlbiglutide, as part of triple therapy, provided effective glucose-lowering and was generally well tolerated.