Health-related quality of life in a randomised placebo-controlled trial of sibutramine in obese patients with type II diabetes.

OBJECTIVE: We evaluated the effects of 12-month treatment with sibutramine 15 mg daily compared with placebo on health-related quality of life (HRQL) in obese type II diabetes patients. We examined the associations between the changes in HRQL and in weight, glycaemic control, and haemodynamic variables. We also explored the predictive value of HRQL and its changes early during treatment. DESIGN: A randomised clinical trial. The subjects were enrolled in a 2-week single-blind run-in period with a modestly hypocaloric diet (700 kcal daily deficit) and then randomised to receive either sibutramine 15 mg (n=114, 60% female) or placebo (n=122, 58% female) once daily with the hypocaloric diet for 12 months. SUBJECTS: Obese (mean BMI 36 kg/m(2) and age 54 y) type II diabetes patients untreated with antidiabetic medications. MEASUREMENTS: The main outcome measures included body weight and HRQL (the RAND 36-Item Health Survey 1.0). RESULTS: The mean weight loss was greater in the sibutramine group (-7.1 kg) than in the placebo group (-2.6 kg, P<0.001). The baseline HRQL was relatively high. There were no significant differences between the treatment groups in glycaemic control or in any of the RAND-36 scales during the study. The scores on physical functioning (PF) and health change (HC) since last year improved in both groups and this improvement was related to weight loss. When HRQL changes were examined in categories of weight loss, the scores on PF and HC increased with >/=5% weight loss, but the scores on vitality (V) and general health (GH) increased only after >/=15% weight loss. Decrease in HbA1c was associated with increases in the scores of PF, GH, V, mental health, and HC. In the sibutramine group, the increase in diastolic blood pressure was associated with the decrease in the scores of PF, physical role functioning, emotional role functioning (ERF), social functioning (SF), and bodily pain. High baseline scores on ERF and SF, and low scores on V predicted weight loss at 12 months. Also, increasing scores on PF and V during the first 3 months predicted weight loss at 12 months. The sum of four dichotomised HRQL variables (baseline ERF >/=75=1 and <75=0; baseline SF>/=80=1 and <80=0; 3-month change in PF>0=1 and 0=1 and /=5% weight loss, but >/=15% weight loss was needed to achieve a cluster of HRQL improvements. The decrease in HbA1c was associated with many HRQL benefits. Poor baseline HRQL and the improvement observed in the first months of treatment may prove to be useful in predicting success in long-term weight loss.

Absence of cardiac valve dysfunction in obese patients treated with sibutramine.

OBJECTIVE: Serotonin-releasing agents prescribed as weight-loss medications have been implicated as a cause of acquired aortic and mitral valve abnormalities. Sibutramine hydrochloride (MERIDIA) is a serotonin and norepinephrine reuptake inhibitor with proven efficacy of weight reduction. The purpose of this study was to determine the incidence of cardiac valve disease in sibutraminetreated patients. RESEARCH METHODS AND PROCEDURES: Obese patients with type 2 diabetes mellitus enrolled in an ongoing double-blind, placebo-controlled, parallel-arm, 12-month study of sibutramine (followed by a 12-month open label extension) underwent transthoracic echocardiographic imaging and color Doppler interrogation for assessment of cardiac valve anatomy and function. RESULTS: A total of 210 patients were evaluated. Of these, 133 were receiving sibutramine (72 in the double-blind period), and 77 were receiving placebo. The mean+/-Standard Deviation age was 54+/-9 years, and the mean duration of treatment was 229+/-117 days (approximately 7.6 months). The prevalence of left-sided cardiac valve dysfunction was low and similar for the two treatment groups (sibutramine 3/133, or 2.3%; placebo 2/77, or 2.6%). All five cases were cases of aortic insufficiency; four were mild, one was severe (in a placebo patient). All three sibutramine cases were patients over age 50; two had a history of systemic hypertension. CONCLUSION: The prevalence of left-sided cardiac valve dysfunction was not higher than background in obese patients treated with sibutramine for an average of 7.6 months.