Persistent Insulin-Sensitizing Effects of Sarpogrelate Hydrochloride, a Serotonin 2A Receptor Antagonist, in Patients With Peripheral Arterial Disease

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Background There is considerable interest in the pleiotropic pharmacological action of sarpogrelate hydrochloride, a novel selective serotonin 2A receptor antagonist. In the present study the persistent insulin-sensitizing effects of sarpogrelate were investigated in non-diabetic and non-medicated diabetic patients with peripheral artery disease (PAD). Methods and Results Indices of insulin resistance (IR) (fasting immunoreactive insulin (IRI) and calculated homeostasis model assessment (HOMA-R)) and adiponectin were measured before and after 2 weeks of sarpogrelate administration (300mg/day) in 24 patients (19 men, 76±9 years) with PAD. Sixteen of the 24 patients were examined after 3 months of treatment for assessment of the chronic effect of sarpogrelate on IR. After 2 weeks of treatment, significant decreases in fasting IRI (p=0.03) and HOMA-R (p=0.024), but not in adiponectin, were observed. After 3 months of treatment, significant decreases in fasting IRI (16.0±10.3 vs 9.2±2.0μU/ml, p=0.03) and HOMA-R (4.30±2.83 vs 2.40±0.74, p=0.025) were maintained. Furthermore, adiponectin was significantly increased (8.11±4.13 vs 9.64±4.37μg/ml, p=0.027). All of the examined HOMA-R had a significant correlation with all of the examined adiponectin (p<0.001, r=-0.441). Conclusions Sarpogrelate has a persistent insulin-sensitizing effect through adiponectin modification and might be beneficial for anti-atherosclerotic therapy, at least, in non-diabetic and non-medicated diabetic patients with PAD.
社団法人日本循環器学会の論文
2006-10-20

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