Effects of Sibutramine on the Treatment of Obesity in Patients with Arterial Hypertension

Abstract

Objective - Effects of Sibutramine on the Treatment of Obesity in Patients with Arterial Hypertension Artigo OriginalThe prevalence of obesity and its associated morbidities has increased in several countries worldwide, including Brazil 1,2 . The increase in body mass index has proved to be a determinant factor for elevation of blood pressure, both for obese and nonobese children and adults 3,4 . In addition, the presence of obesity is related to a 2.5 higher risk of arterial hypertension, mainly in patients with central body fat distribution 5 . Several hypotheses exist for the pathophysiology of arterial hypertension in this obese population. The first and more accepted hypothesis proposes that hyperinsulinemia secondary to insulin resistance existing in these patients leads to greater sympathetic activity and to renal sodium retention, which would account for the increase in pressure levels [6][7][8] . The second hypothesis associates the arterial hypertension existing in these patients with the mechanical compression of renal parenchyma by visceral fat. This leads to hyperactivation of the renin-angiotensinaldosterone system (RAAS), higher sodium reabsorption, and a subsequent elevation in blood pressure by a mechanism independent from insulinemia 9,10 .Even though we have not reached a consensus about the causes of arterial hypertension in the obese, several clinical studies confirm the importance of weight loss to better control blood pressure levels 11,12 .The great challenge has been to find effective clinical treatments, which do not impair blood pressure control, to induce weight loss in hypertensive patients. Of the several treatments available for weight control, we can count on appetite suppressing drugs, which comprise a generic class of drugs derived from amphetamines that act through adrenergic receptors, and, therefore, may aggravate hypertension. More recently, other options include orlistat that inhibits gastrointestinal fat absorption, and sibutramine, an appetite suppressant that blocks serotonin, dopamine, and noradrenaline reuptake 13 .The use of sibutramine is associated with an increase in satiety scores and a lack of decline in 24-hour energy

Can sibutramine alter systemic blood pressure in obese patients? Systematic review and meta-analysis

“…Sibutramine doses -10 mg: six studies [16][17][18]20,22,23 REFERENCES ference in systolic blood pressure was found (the author did not give data on the statistical analyses). However, there was a statistically significant difference favoring the control group, in relation to diastolic blood pressure (CI = 3.51 to 13.29); -Increasing doses, from 5 mg to 20 mg: two studies 19,21 used this scheme and neither of them showed any statistical significance favoring either the experimental or the control group; -Increasing doses, depending on weight loss, up to 20 mg: only one study used this strategy, 9 and it was the only one that found statistical significance for the control group, in relation to both systolic blood and diastolic blood pressure.…”

“…Eight studies 9,[16][17][18][19][20][21][22] presented continuous data that could be analyzed in relation to the outcome of systolic blood pressure (SBP). There were 599 participants in the sibutramine group and 388 in the control group.…”

“…Removing this study from the meta-analysis did not modify the end result. The meta-analysis on these last two studies 16,18 began with participants presenting mean SBP greater than 140 mmHg, and none of them showed increased statistical significance with regard to SBP.…”

“…This variable was capable of influencing the result, depending on the inclusion criteria limits imposed: BMI less than 30 kg/m²: six studies; 16,19,21,[25][26][27] BMI greater than 40 kg/m 2 :, three studies; 9,18,20 BMI up to 50 kg/m 2 :, one study. 18 Despite the different inclusion criteria relating to BMI, the mean for all participants was between 33 and 35 kg/m 2 , except for one study 18 that had a higher mean of 39.5 kg/m 2 and another 26 that had a smaller mean of 30.8 kg/m 2 .…”

“…This observation confirms the concept of the importance of diet, independent of the drugs used. In the meta-analysis relating to this outcome, two studies 16,18 began with participants whose mean DBP was greater than 90 mmHg, and neither of them increased the statistical significance of DBP.…”