Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure.
The incretin hormone glucagon-like peptide-1 (GLP-1) and its analogs are currently emerging as antidiabetic medications. GLP-1 improves left ventricular ejection fraction (LVEF) in dogs with heart failure (HF) and in patients with acute myocardial infarction. We studied metabolic and cardiovascular effects of 48-h GLP-1 infusions in patients with congestive HF. In a randomized, double-blind crossover design, 20 patients without diabetes and with HF with ischemic heart disease, EF of 30 +/- 2%, New York Heart Association II and III (n = 14 and 6) received 48-h GLP-1 (0.7 pmol.kg(-1).min(-1)) and placebo infusion. At 0 and 48 h, LVEF, diastolic function, tissue Doppler regional myocardial function, exercise testing, noninvasive cardiac output, and brain natriuretic peptide (BNP) were measured. Blood pressure, heart rate, and metabolic parameters were recorded. Fifteen patients completed the protocol. GLP-1 increased insulin (90 +/- 17 pmol/l vs. 69 +/- 12 pmol/l; P = 0.025) and lowered glucose levels (5.2 +/- 0.1 mmol/l vs. 5.6 +/- 0.1 mmol/l; P < 0.01). Heart rate (67 +/- 2 beats/min vs. 65 +/- 2 beats/min; P = 0.016) and diastolic blood pressure (71 +/- 2 mmHg vs. 68 +/- 2 mmHg; P = 0.008) increased during GLP-1 treatment. Cardiac index (1.5 +/- 0.1 l.min(-1).m(-2) vs. 1.7 +/- 0.2 l.min(-1).m(-2); P = 0.54) and LVEF (30 +/- 2% vs. 30 +/- 2%; P = 0.93), tissue Doppler indexes, body weight, and BNP remained unchanged. Hypoglycemic events related to GLP-1 treatment were observed in eight patients. GLP-1 infusion increased circulating insulin levels and reduced plasma glucose concentration but had no major cardiovascular effects in patients without diabetes but with compensated HF. The impact of minor increases in heart rate and diastolic blood pressure during GLP-1 infusion requires further studies. Hypoglycemia was frequent and calls for caution in patients without diabetes but with HF.
Halbirk
Mads
M
Dept. of Cardiology, Aarhus Univ. Hospital, Skejby, Denmark. mshl@ki.au.dk
Nørrelund
Helene
H
Møller
Niels
N
Holst
Jens Juul
JJ
Schmitz
Ole
O
Nielsen
Roni
R
Nielsen-Kudsk
Jens Erik
JE
Nielsen
Søren Steen
SS
Nielsen
Torsten Toftegaard
TT
Eiskjaer
Hans
H
Bøtker
Hans Erik
HE
Wiggers
Henrik
H
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D002302:Cardiac Output / Q000502:physiology; D002908:Chronic Disease; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D052216:Glucagon-Like Peptide 1