A randomized dose-finding study demonstrating the efficacy and tolerability of albiglutide in Japanese patients with type 2 diabetes mellitus

Abstract

Objective:

To investigate the optimal dosage/regimen and to evaluate the efficacy and safety of albiglutide in Japanese patients with type 2 diabetes mellitus.

Research design and methods:

This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose-ranging, superiority study in Japanese patients with type 2 diabetes mellitus. Patients (n = 215) who were treatment naive or washed out of one oral antidiabetic drug were randomized to placebo or albiglutide 15 mg weekly, 30 mg weekly, or 30 mg every other week (biweekly).

Clinical trial registration:

NCT01098461.

Main outcome measures:

The primary end point was the change from baseline in HbA_1c at week 16, measured using the Japan Diabetes Society standardization scheme and presented here using the National Glycohemoglobin Standardization Program equivalents. Other measures of efficacy as well as safety and population pharmacokinetics and pharmacokinetics/pharmacodynamics of albiglutide were assessed.

Results:

Baseline HbA_1c was 8.53%. There was a statistically significant difference between each albiglutide treatment group and placebo for change from baseline in HbA_1c at week 16, with treatment effects of −0.89% for 15 mg weekly, −1.55% for 30 mg weekly, and −1.10% for 30 mg biweekly (P < 0.0001 for all groups vs placebo). By week 16, 63.0% and 33.3% of patients in the 30 mg weekly albiglutide group compared with 6.0% and 0% of patients in the placebo group achieved HbA_1c <7.4% and <6.9%, respectively. No serious adverse events were related to study therapy; no deaths occurred. Nasopharyngitis was the most frequently reported adverse event in all treatment groups (n = 43 [20.3%]).

Conclusions:

Albiglutide exhibited therapeutic hypoglycemic effects with good tolerability among Japanese patients with type 2 diabetes mellitus; the 30 mg weekly dose was the most efficacious in this study. The 16 week duration of the study prevents generalizing these conclusions to longer treatment periods.

Keywords::

• Albiglutide
• Diabetes mellitus, Type 2
• Glucagon-like peptide-1
• Japanese

Transparency

Declaration of funding

This study was funded by GlaxoSmithKline. All authors meet ICMJE authorship criteria. All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Y.S. and N.I. contributed to the study design and concept and design of the manuscript. H.N. contributed to the concept and design of the manuscript and supervision of the clinical study. I.O. and H.M. contributed to the study design and concept and design of the manuscript and operated the clinical study. M.B. contributed to the study design and concept and design of the manuscript and analyzed and interpreted data. J.Y. and S.J. contributed to the concept and design of the manuscript and analyzed and interpreted the data. M.C.H. collected, assembled, analyzed, and interpreted the data. All authors approved the final manuscript.

Declaration of financial/other relationships

H.M., J.Y., M.C.H., S.J., E.L. and H.N. are employees and stockholders of GlaxoSmithKline. I.O. is an employee of GlaxoSmithKline. M.B. is a former employee of and stockholder of GlaxoSmithKline. Y.S. is a consultant/advisor for Taisho Pharmaceutical Co. Ltd, Sanofi-Aventis, GlaxoSmithKline, Novo Nordisk A/S, Eli Lilly and Company, Takeda Pharmaceutical Company Ltd, and Otsuka Pharmaceutical Group. N.I. is a consultant/advisor for Takeda Pharmaceutical Company Ltd, Ono Pharmaceutical Co. Ltd, Taisho Pharmaceutical Co. Ltd, Nippon Boehringer Ingelheim Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Kissei Pharmaceutical Co. Ltd, and GlaxoSmithKline K.K.

CMRO Peer Reviewer 1 has no relevant financial or other relationships to disclose. Peer Reviewer 2 is a CMRO editorial board member and has been a consultant to a number of pharmaceutical companies including GlaxoSmithKline, Takeda, Novo Nordisk, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, Pamlabs, Astra-Zeneca, Abbott, Bristol–Myers Squibb, and Boehringer Ingelheim.

Acknowledgments

The authors thank Yukiko Imai (GlaxoSmithKline) and Fred Yang (GlaxoSmithKline) for statistical analysis support; Charles Smith and Prapoch (Keng) Watanalumlerd (Pharmaceutical Product Development, LLC) for PK analysis support; and Beth Burke, Joelle Suchy, Kristi Allard, and Brett Scott (MediTech Media) and Diana Talag (PharmaWrite) for assistance in preparation of the manuscript, which was funded by GlaxoSmithKline.

Previous presentation: This study was presented as two posters (973-P, 1020-P) at the 72nd Scientific Session of the American Diabetes Association, 8–12 June 2012, Philadelphia, PA, USA.