Persistent insulin-sensitizing effects of sarpogrelate hydrochloride, a serotonin 2A receptor antagonist, in patients with peripheral arterial disease.
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).


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 (300 mg/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+/-2.0 microU/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+/-4.37 microg/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.
Kokubu
Nobuaki
N
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-0061, Japan. kokubu@sapmed.ac.jp
Tsuchihashi
Kazufumi
K
Yuda
Satoshi
S
Hase
Mamoru
M
Eguchi
Mariko
M
Wakabayashi
Takeru
T
Hashimoto
Akiyoshi
A
Nakata
Tomoaki
T
Miura
Tetsuji
T
Ura
Nobuyuki
N
Nagao
Kazuhiko
K
Tsuzuki
Masahiro
M
Wakabayashi
Chikashi
C
Shimamoto
Kazuaki
K
D052242:Adiponectin / Q000097:blood; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000188:drug therapy / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D013386:Succinates / Q000494:pharmacology / Q000627:therapeutic use*
D052242:Adiponectin; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate