Chronic dipeptidyl peptidase-4 inhibition with sitagliptin is associated with sustained protection against ischemic left ventricular dysfunction in a pilot study of patients with type 2 diabetes mellitus and coronary artery disease.
Circ Cardiovasc Imaging
; 7(2): 274-81, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24503784
ABSTRACT
BACKGROUND:
The incretin hormone, glucagon-like peptide-1, promotes myocardial glucose uptake and may improve myocardial tolerance to ischemia. Endogenous glucagon-like peptide-1 (7-36) is augmented by pharmacological inhibition of dipeptidyl peptidase-4. We investigated whether chronic dipeptidyl peptidase-4 inhibition by sitagliptin protected against ischemic left ventricular dysfunction during dobutamine stress in patients with type 2 diabetes mellitus and coronary artery disease. METHODS ANDRESULTS:
A total of 19 patients with type 2 diabetes mellitus underwent dobutamine stress echocardiography with tissue Doppler imaging on 2 separate occasions the first (control) while receiving oral hypoglycemic agents, and the second after the addition of sitagliptin (100 mg once daily) for ≈4 weeks. Sitagliptin increased plasma glucagon-like peptide-1 (7-36) levels and, at peak stress, enhanced both global (ejection fraction, 70.5±7.0 versus 65.7±8.0%; P<0.0001; mitral annular systolic velocity, 11.7±2.6 versus 10.9±2.3 cm/s; P=0.01) and regional left ventricular function, assessed by peak systolic velocity and strain rate in 12 paired, nonapical segments. This was predominantly because of a cardioprotective effect on ischemic segments (strain rate in ischemic segments, -2.27±0.65 versus -1.98±0.58 s(-1); P=0.001), whereas no effect was seen in nonischemic segments (-2.19±0.48 versus -2.18±0.54 s(-1); P=0.87). At 30 minutes recovery, dipeptidyl peptidase-4 inhibition mitigated the postischemic stunning seen in the control scan.CONCLUSIONS:
The addition of dipeptidyl peptidase-4 inhibitor therapy with sitagliptin to the treatment regime of patients with type 2 diabetes mellitus and coronary artery disease is associated with a sustained improvement in myocardial performance during dobutamine stress and a reduction in postischemic stunning. CLINICAL TRIAL REGISTRATION URL http//www.isrctn.org. Unique identifier ISRCTN61646154.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pirazinas
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Triazóis
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Doença da Artéria Coronariana
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Isquemia Miocárdica
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Disfunção Ventricular Esquerda
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Dipeptidil Peptidase 4
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Diabetes Mellitus Tipo 2
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Ventrículos do Coração
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Reino Unido