Efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide (HARMONY 2): 52 week primary endpoint results from a randomised, placebo-controlled trial in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise

Abstract

Aims/hypothesis: Additional safe and effective therapies for type 2 diabetes are needed, especially ones that do not cause weight gain and have a low risk of hypoglycaemia. The present study evaluated albiglutide as monotherapy.

Methods: In this placebo-controlled study, 309 patients (aged ≥ 18 years) with type 2 diabetes inadequately controlled by diet and exercise and who were not using a glucose-lowering agent (HbA1c 7.0-10.0% [53.00-85.79 mmol/mol], body mass index 20-45 kg/m(2), and fasting C-peptide ≥ 0.26 nmol/l) were randomised (1:1:1 on a fixed randomisation schedule using an interactive voice response system) to receive once-weekly albiglutide 30 mg (n = 102) or 50 mg (n = 102) or matching placebo (n = 105). The study treatments were blinded to both patients and study personnel. All study data were collected at individual patient clinic visits. The primary efficacy endpoint was change in HbA1c from baseline to week 52. The primary analysis was applied to the intent-to-treat population. Additional efficacy and safety endpoints were assessed.

Results: At week 52, both albiglutide 30 mg and 50 mg were superior to placebo in reducing HbA1c. The least-squares means treatment difference from placebo was -0.84% (95% CI -1.11%, -0.58%; p < 0.0001) with albiglutide 30 mg and -1.04% (-1.31%, -0.77%; p < 0.0001) with albiglutide 50 mg. Injection-site reactions were reported more frequently with albiglutide (30 mg: 17.8%; 50 mg: 22.2%) than with placebo (9.9%). Other commonly reported adverse events included nausea, diarrhoea, vomiting and hypoglycaemia; the incidences of these were generally similar across treatment groups.

Conclusions/interpretation: Albiglutide is safe and effective as monotherapy and significantly lowered HbA1c levels over 52 weeks, did not cause weight gain, and had good gastrointestinal tolerability and a low rate of hypoglycaemia compared with placebo. Trial registration ClinicalTrials.gov NCT00849017 Funding This study was sponsored by GlaxoSmithKline.

Keywords: Albiglutide; GLP-1 agonist; Randomised controlled trial; Type 2 diabetes.

Fig. 1

Patient disposition throughout the study. The study was ongoing at the time of data analysis and the number of patients who withdrew because of an adverse event by week 52 was reconciled to include two additional patients in each of the albiglutide treatment groups

Fig. 2

(a, b) Mean change in HbA_1c (a) and FPG (b) from baseline through to week 52. Data are means ± SEM. Blue diamonds, placebo (n = 99); green squares, albiglutide 30 mg (n = 100); red triangles, albiglutide 50 mg (n = 97) uptitration at week 12. To convert values for HbA_1c in DCCT % into mmol/mol, subtract 2.15 and multiply by 10.929. (c) Kaplan–Meier plot of probability of hyperglycaemic rescue. Blue line, placebo; green line, albiglutide 30 mg; red line, albiglutide 50 mg. HbA_1c and FPG analyses were for the ITT population with LOCF; Kaplan–Meier plot of probability of hyperglycaemic rescue was for the ITT population

Fig. 3

Nausea/vomiting (a) and diarrhoea events (b) over time to week 52. Analyses are for the safety population, defined as all randomised patients who received at least one dose of study drug. Blue lines, placebo (n = 101); green lines, albiglutide 30 mg (n = 101); red lines, albiglutide 50 mg (n = 99) uptitration at week 12