Randomized Placebo-Controlled Trial of Long-Term Treatment with Sibutramine in Mild to Moderate Obesity

,

Original Research

Randomized Placebo-Controlled Trial of Long-Term Treatment with Sibutramine in Mild to Moderate Obesity

J Fam Pract. 2001 June;50(6):505-512

By

Ian G. Smith, MB, ChB

References

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OBJECTIVE: We assessed the long-term weight reduction efficacy, tolerability, and safety of sibutramine used once daily in conjunction with behavior modification to treat mild to moderate obesity.

STUDY DESIGN: This was a double-blind randomized placebo-controlled parallel-group comparative study of sibutramine 10 mg or 15 mg (or placebo) once daily for 1 year, given with dietary advice.

POPULATION: A total of 485 obese men and women with uncomplicated obesity were included (mean age=42 years; mean body mass index=32.7 kg/m²).

OUTCOMES: measured The outcomes were mean weight loss, percentage losing more than 5% or 10% of their body weight, and adverse drug effects.

RESULTS: Among patients completing the study, those taking sibutramine 10 mg or 15 mg had greater mean weight loss compared with placebo at 12-month assessment (P <.001). Changes in body weight from baseline to end point were -1.6 kg for those taking placebo, -4.4 kg for those taking sibutramine 10 mg (P <.01, last observation carried forward [LOCF]), and -6.4 kg for those taking sibutramine 15 mg (P <.001, LOCF). For placebo patients, 20% lost 5% or more of their body weight compared with 39% of patients taking sibutramine 10 mg and 57% taking sibutramine 15 mg. Only 7% of the patients taking placebo lost 10% or more of their body weight, compared with 19% taking sibutramine 10 mg and 34% taking sibutramine 15 mg (P <.001 for both 10 mg and 15 mg vs placebo, and for both Ž5% and Ž10%).

CONCLUSIONS: Sibutramine 10 mg or 15 mg once daily given with dietary advice produces and maintains statistically and clinically significantly greater weight loss than dietary advice alone (placebo) throughout a 12-month treatment period, and is safe and well tolerated.

Obesity is a common problem, with significant health costs and associated morbidity; rates of overweight and obesity continue to increase in the United States^1,2 and Europe.³ In a typical general practice setting of 10,000 patients in the United Kingdom, approximately 1600 men and 1300 women could be expected to be overweight, and another 360 men and 700 women would need management of their obesity.⁴ Obesity predisposes patients to cardiovascular disease and hypertension,⁵ diabetes mellitus,⁶ hormone-related cancers,⁷ gallbladder disease,⁸ musculoskeletal disorders,⁹ sleep apnea,¹⁰ and generalized bodily pain.¹¹ It has a detrimental effect on social well-being,¹² decreases longevity,¹³ and imposes a tremendous financial and time burden on health care systems¹⁴; yet even a moderate amount of intentional weight loss (approximately 5%-10%) may significantly reduce the risk of mortality among subjects with medical complications of obesity.¹⁵

Increasingly, the major share of the primary effort to lower weight is falling on the general practice physician.¹⁶ Despite this, only 42% of obese patients seeking medical help are advised by their health professionals to lose weight; however, this telephone survey may suffer from a significant recall bias.¹⁷ Within the medical specialties, including family practice, internal medicine, and endocrinology, approximately 50% of physicians express interest in treating obesity in their practices.^16,18

Current treatment plans include mostly behavioral interventions, such as diet and exercise, along with behavior modification.¹⁹ These generally have a poor success rate, and in one study, long-term follow-up of weight maintenance after a 12-week very-low-calorie diet showed that patients regained the weight lost at a rate of 2.5% per month.²⁰ Although pharmacotherapy can be an important component of a weight loss program, safety issues have led to the withdrawal of some medications from the market. Studies with these have shown, however, that weight loss with pharmacotherapy can result in significant health benefits.^21-26

Sibutramine (Meridia; Knoll Pharmaceuticals, Nottingham, United Kingdom) is a new pharmacotherapy alternative. It is a serotonin-norepinephrine reuptake inhibitor (SNRI) that produces dose-related weight loss by enhancing postingestive satiety and by increasing energy expenditure.^21,27-29 Twelve months after weight reduction on a 4-week very-low-calorie diet, 75% of the patients taking sibutramine maintained 100% of their weight loss. This is a significantly greater percentage than the 42% who maintained 100% of weight loss in the nonsibutramine control group (P <.01).^30,31 Our study of sibutramine, carried out in a primary care general practice setting, was designed to determine the long-term efficacy, tolerability, and safety of dosages of 10 mg and 15 mg of sibutramine, which have been identified as effective and well tolerated in previous studies.^31,32 We also carried out analysis of improvements in risk factors resulting from 5% and 10% body weight loss.

Methods

The Nottinghamshire Independent Ethics Committee (Boots) approved our study, and all patients gave informed consent in writing. Our study was conducted in accordance with the Declaration of Helsinki (1983 revision).