Effects of sibutramine on abdominal fat mass, insulin resistance and blood pressure in obese hypertensive patients.
OBJECTIVE
The objective of this study is to assess the effects of sibutramine on body weight, body fat distribution, insulin resistance, plasma leptin, lipid profile and blood pressure profiles in hypertensive obese patients.


METHODS
Eighty-six central obese hypertensive patients (BMI = 39 +/- 5 kg/m(2), 84% of women, 48 +/- 8.5 years old) were placed on a hypocaloric diet and placebo therapy for 4 weeks. They were then randomized to receive sibutramine (10 mg) or placebo for 24 weeks. Both, before therapy and at the end of the study, the waist and hip circumferences were measured and the waist/hip ratio (WHR) was calculated; abdominal ultrasonography was performed in order to estimate the amount of subcutaneous fat (SF) and visceral fat (VF), and the visceral/subcutaneous ratio. Beyond HOMA-r, another insulin resistance index (IRIp) was calculated by means of the formula: peak of blood glucose after oral glucose load x plasma insulin level/10(4). Fasting plasma leptin and lipid levels were also determined.


RESULTS
Sibutramine induced greater weight reduction than placebo (6.7 vs. 2.5%, p < 0.001). Reductions in WHR (0.97 +/- 0.08 vs. 0.94 +/- 0.07, p < 0.01), IRIp (0.11 +/- 0.07 vs. 0.09 +/- 0.06 mmol mu/l(2)) and VF (6.4 +/- 2.4-6.0 +/- 2.4 cm, p < 0.01) were observed only with sibutramine. Plasma leptin decreased with placebo (24 +/- 15 vs. 18 +/- 10 UI/l, p < 0.01), but not with sibutramine (18.8 +/- 8.4 vs. 18.2 +/- 13.2 UI/l). No clinically significant change in lipid profile was observed in both groups. Moreover, office and 24-h blood pressure values did not change during placebo or sibutramine therapy, whereas a significant increase in office heart rate, from 78.3 +/- 7.3-82 +/- 7.9 b.p.m., p = 0.02, was observed with sibutramine.


CONCLUSIONS
Sibutramine therapy induced greater body weight loss than placebo in hypertensive obese patients. This was associated with WHR reduction, decreases in VF and insulin resistance. The maintenance of leptin levels during sibutramine therapy may be important to avoid weight recovery, although this finding must be confirmed by other prospective studies.
Faria
A N
AN
Endocrinology and Nephrology Divisions, Hospital do Rim e da Hipertensão, Universidade Federal de São Paulo, São Paulo, Brazil. ale_faria@uol.com.br
Ribeiro Filho
F F
FF
Kohlmann
N E
NE
Gouvea Ferreira
S R
SR
Zanella
M T
MT
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001067:Appetite Depressants / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003503:Cyclobutanes / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D049629:Waist-Hip Ratio; D015431:Weight Loss
D000959:Antihypertensive Agents; D001067:Appetite Depressants; D003503:Cyclobutanes; D020738:Leptin; D008055:Lipids; C058254:sibutramine