Author + information
- Received February 27, 2015
- Revision received January 4, 2016
- Accepted January 20, 2016
- Published online July 1, 2016.
- John J. Lepore, MDa,∗ (, )
- Eric Olson, PhDa,
- Laura Demopoulos, MDa,
- Thomas Haws, BSb,
- Zixing Fang, PhDc,
- April M. Barbour, PhDd,
- Michael Fossler, PharmD, PhDd,
- Victor G. Davila-Roman, MDe,
- Stuart D. Russell, MDf and
- Robert J. Gropler, MDg
- aMetabolic Pathways and Cardiovascular Therapeutic Area Unit, GlaxoSmithKline, King of Prussia, Pennsylvania
- bClinical Pharmacology Science and Study Operations, GlaxoSmithKline, King of Prussia, Pennsylvania
- cQuantitative Sciences, Clinical Statistics, GlaxoSmithKline, King of Prussia, Pennsylvania
- dClinical Pharmacology Modeling and Simulation, GlaxoSmithKline, King of Prussia, Pennsylvania
- eCardiovascular Imaging and Clinical Research Core Laboratory, Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
- fDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
- gMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
- ↵∗Reprint requests and correspondence:
Dr. John J. Lepore, GlaxoSmithKline, 1250 Collegeville Road, Collegeville, Pennsylvania 19426.
Objectives This study sought to determine if glucagon-like peptide (GLP)-1 ameliorates myocardial metabolic abnormalities in chronic heart failure.
Background Albiglutide (GSK716155) is a GLP-1 agonist indicated for type 2 diabetes.
Methods We performed a randomized, placebo-controlled study evaluating 12 weeks of albiglutide in New York Heart Association II or III subjects with ejection fraction <40%. Subjects received weekly placebo (n = 30) or albiglutide 3.75 mg (n = 12), 15 mg (n = 13), or 30 mg (n = 27). The primary comparison was between albiglutide 30 mg and placebo. Assessments included echocardiography, 6-minute-walk test, and peak oxygen consumption. In a subgroup of patients, myocardial glucose and oxygen use were assessed. Endpoints are reported as change from baseline ± SE.
Results Albiglutide 30 mg compared with placebo did not improve change from baseline in left ventricular ejection fraction (2.4% [1.1%] vs. 4.4% [1.1%]; p = 0.22), 6-min walk test (18  m vs. 9  m; p = 0.58), myocardial glucose use (p = 0.59), or oxygen use (p = 0.25). In contrast, albiglutide 30 mg versus placebo improved change from baseline in peak oxygen consumption (0.9 [0.5] ml/kg/min vs. -0.6 [0.5] ml/kg/min; p = 0.02). Albiglutide was well tolerated.
Conclusions Although there was no detectable effect of albiglutide on cardiac function or myocardial glucose use, there was a modest increase in peak oxygen consumption, which could have been mediated by noncardiac effects. (A Multi-center, Placebo-controlled Study to Evaluate the Safety of GSK716155 and Its Effects on Myocardial Metabolism, Myocardial Function, and Exercise Capacity in Patients With NYHA Class II/III Congestive Heart Failure; NCT01357850)
Funding for this study was provided by GlaxoSmithKline (NCT01357850). Drs. Lepore, Olson, Demopoulos, and Fang and Mr. Haws are employees of and have stock options and own stock in GlaxoSmithKline. Dr. Barbour was an employee of GlaxoSmithKline at the time of this study and owns stock in GlaxoSmithKline; she is currently an employee of Merck & Co., Inc., and owns stock in Merck & Co., Inc. Dr. Fossler was an employee of GlaxoSmithKline at the time of this study and held stock and stock options in GlaxoSmithKline. Dr. Davila-Roman has received funding from various pharmaceutical companies. Drs. Russell and Gropler have received funding from GlaxoSmithKline for study administration; and have received reimbursement for travel-related expenses to investigator meetings by GlaxoSmithKline.
- Received February 27, 2015.
- Revision received January 4, 2016.
- Accepted January 20, 2016.
- 2016 American College of Cardiology Foundation