Dossier: Diabetes: Basic Research and Clinical Approach
Efficacy of sibutramine, orlistat and combination therapy on short-term weight management in obese patients

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Abstract

Objectives. – To compare changes in anthropometric measures [body mass index (BMI), body weight] of obese patients treated with diet and exercise alone or additionally sibutramine, orlistat or the combination of both drugs, respectively. To describe encountered adverse effects.

Methods. – Short-term (12 weeks), randomized, open-labeled trial. A total of 86 patients (18.6% male, age 41.1 ± 8.7 years, BMI: 36.11 ± 4.34 kg/m2) were randomized to (1) sibutramine group (10 mg/d, n = 22), or (2) orlistat group (3 × 120 mg/d, n = 25), or (3) combination group (10 mg sibutramine/d + 3 × 120 mg orlistat/d, n = 20), or (4) diet group (n = 19). The primary outcome parameter was a decrease in BMI. Additionally patient-reported adverse effects were reported.

Results. – The four interventional groups displayed decreases in BMI as follows: (1) –4.41 ± 1.26 kg/m2; (2) –3.64 ± 0.97 kg/m2; (3) –5.12 ± 1.44 kg/m2 and (4) –2.52 ± 1.36 kg/m2; with the diet group showing the significantly lowest decrease in BMI compared to the orlistat (P = 0.004), sibutramine (P < 0.001) or the combination groups (P < 0.001), respectively. Decreases in BMI did not statistically differed between the sibutramine group and the combination therapy group (P = 0.072). However, both treatment groups were significantly more efficient in decreasing BMI than the orlistat group (P < 0.001). In addition to well-known side effects, such as gastrointestinal disturbances, headache and dry mouth, newly described adverse effects were self-reported hypermenorrhea (13.6%, n = 3) with sibutramine and forgetfulness with orlistat (24%, n = 6).

Conclusion. – In our study pharmacotherapy showed significant better results in the short-term management of obesity than dietary regimens alone. Sibutramine and sibutramine in combination with orlistat seemed to be equally effective in terms of weight reduction compared to orlistat monotherapy. Attention should be paid to the possibility of adverse effects.

Introduction

According to the World Health Organization (WHO), 10–15% of all European men and 15–25% of all European women are obese and the problem of overweight has been extending gradually, turning obesity into one of the leading mortality causes worldwide [1], [2], [3], [4], [5]. Furthermore, obesity is a well-known risk factor for the metabolic syndrome [6], type 2 diabetes mellitus [6], [7], coronary heart disease [8] and stroke [9]. Even moderate weight reduction of 5–10% has been shown to significantly improve the majority of these risk factors [10], [11]. Even though lifestyle modifications including diet and exercise regimens are still considered the cornerstones of obesity management; in a considerable number of patients these approaches are of limited success. Pharmacological agents can be useful adjuncts to exercise and dietary therapy, especially when associated metabolic and vascular risk factors justify aggressive weight management interventions for the patient [12]. In recent years, several new oral pharmacological agents with different acting mechanisms have been introduced for the purpose of antiobesity therapy. Sibutramine hydrochloride is a central acting serotonin and noradrenalin reuptake-inhibitor (SNRI) with weight reducing properties [13]. Although its mechanisms of action are not fully clear yet [14], sibutramine is said to execute its effect via a dual action of enhancing satiety and increasing energy expenditure by enhancing metabolic rate [13]. Orlistat, the first agent in the lipase inhibitor class of antiobesity drugs [15], has a peripheral, selective inhibitory acting mechanism on gastric and pancreatic lipases, leading to a dose dependant reduction in dietary fat absorption [16], with a maximum of 30% [17]. Although many studies have been focusing on the efficacy and safety of either sibutramine or orlistat alone in contrast to placebo, very little is known about comparison of the performance of these drugs, as well as the effects of combining sibutramine and orlistat. The aim of this study was to compare the efficacy of sibutramine and orlistat, in mono- and combination therapy, with the effect of non-pharmaceutical therapy on BMI of obese patients. Furthermore, adverse effects in the four different interventional groups were monitored.

Section snippets

Materials and methods

The local ethical committee approved the study protocol. The study was carried out in accordance with the Declaration of Helsinki with all patients giving their informed consent.

The study was designed as a prospective, short-term, open-labeled randomized trial and conducted at a hospital internal medicine outpatient clinic unit. The follow-up period was 3 months. Inclusion criteria were age over 18 and under 60 years, history of at least one unsuccessful attempt to lose weight by dietary

Results

Demographic and baseline clinical characteristics of the study population are shown in Table 1. There was no statistically significant difference between the groups concerning baseline demographic and main outcome parameters. Eighty-six of a total of 104 initially enrolled patients completed the study with a drop out rate of 17.30% mainly because of failure to attend the clinical appointments. There was only one case in the combination therapy group, with allergic side effects occurring 1 h

Discussion

In our study, we aimed at comparing the effects of two oral antiobesity drugs, sibutramine and orlistat and their combination, on obesity in contrast to a non-pharmaceutical approach with calorie-restricted diet and exercise regimen, which turned out to be least effective on weight loss and BMI decrease, producing statistically significant differences with all other interventional groups. These results are in accordance with many randomized controlled trials, conducted with either of the two

Conclusion

According to our study results, compared to pharmaceutical intervention, diet and exercise regimen were significantly less effective in terms of weight loss and BMI decrease in short-term obesity management. When comparing efficacy of mono-therapy of the two drugs, sibutramine proved to be more effective in terms of weight management than orlistat. Combination therapy was more effective than orlistat mono-therapy, but showed no superior effect compared to sibutramine mono-therapy. Although the

Acknowledgements

The authors wish to express their gratitude to Dr Richard Atkinson (University of Wisconsin Medical School, Beers-Murphy Clinical Nutrition Center), Dr Hans Hauner (German Diabetes Research Institute, Heinrich-Heine-University Duesseldorf), Dr D. De Zeeuw, Dr R.H. Henning and Dr Y.E. Kocabasoglu (University of Groeningen, Faculty of Medicine, Department of Clinical Pharmacology) for their valuable suggestions and critically reading the manuscript.

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