Effects of Albiglutide in Patients With Heart Failure

Study Questions:

What is the effect of glucagon-like peptide (GLP)-1 on myocardial metabolic abnormalities in chronic heart failure?

Methods:

The investigators performed a randomized, placebo-controlled study evaluating 12 weeks of albiglutide in New York Heart Association (NYHA) class 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 ± standard error.

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-minute walk test (18 [12] m vs. 9 [11] 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:

The authors concluded that 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.

Perspective:

This study reports that albiglutide, a long-acting GLP-1 agonist, with weekly administration of for 12 weeks did not show benefit on cardiac metabolic or echocardiographic parameters in patients with heart failure with reduced ejection fraction and NYHA functional class II-III symptoms, although a modest improvement in peak oxygen consumption was demonstrated in patients on albiglutide compared with placebo. Because the results of the study do not demonstrate an effect of albiglutide on resting cardiac functional or metabolic measures, the effect on peak oxygen consumption suggests the possibility of extracardiac GLP-1 effects, or an effect on cardiac performance. Given the clinical need and potential for benefit, additional metabolic interventions should continue to be evaluated in the treatment of chronic heart failure.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Echocardiography/Ultrasound

Keywords: Echocardiography, Exercise Tolerance, Glucagon-Like Peptide 1, Heart Failure, Metabolism, Myocardium, Oxygen Consumption, Stroke Volume


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