Ian G. Smith, MB, ChB, on behalf of the members of the Sibutramine Clinical Study 1047 Team Michael A. Goulder, BSc Chorley and Nottingham, England Submitted, revised, February 25, 2001. From Synexus LTD, Chorley (I.G.S.) and Biostatistics and Data Management, Knoll Limited, Nottingham (M.A.G.). Reprint requests should be addressed to Ian G. Smith, MB, ChB, Synexus LTD, Sandringham House, Ackhurst Park, Chorley PR7 1NY United Kingdom. E-mail: ian.smith@synexus.co.uk
References
The plateau in weight loss observed at 6 months and maintained while having treatment is consistent with observations in other long-term studies of drug treatment in uncomplicated obese patients.26,37 On the basis of other studies of weight loss, the regain of weight after cessation of treatment is not unexpected. The rates of completion of the study, although low, probably reflect what might be expected to occur in a general practice setting and are consistent with completion rates of weight loss programs in general.37
The response rate at the 5% and 10% weight-reduction thresholds, with changes in waist circumference and in waist/hip ratio, were chosen for analysis in part because weight loss at these levels may ameliorate obesity-related disease.37-42 Sustained moderate weight loss may be expected to bring about a reduction in blood pressure, hypertension, and dyslipidemia.43 The small mean changes in blood pressure seen in the sibutramine groups were not unexpected given the norepinephrine-reuptake inhibitory properties of sibutramine. In clinical practice, any clinically significant changes that may occur should be detected by routine monitoring of vital signs. Of note, even in the current setting, where approximately 8% of patients were being treated with concomitant therapies related to cardiovascular disease, no patients were withdrawn (0%) because of elevated blood pressure.
Limitations
There were limitations to the general applicability of our study results to family practice. The treatment was limited to those patients who first demonstrated they could adhere to a weight loss program. Although the family practitioner may have some background information concerning this capability for a candidate for sibutramine treatment, general documentation may not be available for all candidates. Also, only 53% of the randomized patients completed this 1-year weight loss study. In addition, generally patients who stop weight loss treatment gain weight; however, the Sibutramine Trial in Obesity Reduction and Maintenance44 demonstrated that weight loss can be maintained safely with sibutramine for up to 2 years. Another limitation to applicability of the study is the detailed depression and anxiety profile carried out for some patients enrolled. Such analysis is not practical or needed before sibutramine use in a family practice setting, and this analysis is not included in recently initiated studies. This was a generally healthy obese patient population with few comorbidities, and they were not depressed or anxious. That may limit the ability to generalize these findings to obese patients overall.
Conclusions
Dosages of sibutramine 10 mg or 15 mg administered once daily in a primary care general practice setting to patients with mild to moderate uncomplicated obesity produced statistically and clinically significant weight reduction that was maintained over a 12-month treatment period. Sibutramine was safe and well tolerated at both 10-mg and 15-mg once-daily doses. Further studies in patients with medical complications of obesity are under way to evaluate the efficacy of sibutramine-induced weight loss on the comorbidities and risk factors associated with obesity.
Acknowledgments
The author would like to thank the Sibutramine Clinical Study 1047 Team for their contributions, especially J Hosie, I James, and SP Jones. Competing interests: This study was funded by Knoll Pharmaceuticals, the manufacturer of sibutramine.
