Weight loss drugs have modest effects
Ten trials combining pharmacologic and behavioral interventions involved a total of 1294 obese adolescents ages 12 to 19. All evaluated short-term weight loss effects of either sibutramine (10-15 mg/d) or orlistat (120 mg tid). Trials ranged from 3 to 12 months. Participants in both the control and intervention groups received behavioral counseling.
The trials all favored the treatment groups, although not all of the results were statistically significant. Trials of longer duration (12 months) had more favorable results than those lasting 6 months.
The largest sibutramine trial (n=498) reported a mean BMI reduction of 2.9 in the treatment group, compared with a reduction of 0.3 in the control group (P<.001). This corresponds to an average weight loss of 14 lb in the intervention group, vs 4.2 lb in the control group, after 12 months.
The largest orlistat trial (n=539) reported a mean BMI reduction in the treatment group of 0.6, vs 0.3 in the control group (P<.001)—an average weight loss of 4.2 lb in the intervention group, compared with 2.1 lb among the controls after 12 months. None of the trials evaluated weight change after cessation of the study drug, and none compared orlistat with sibutramine.
Adverse effects in the sibutramine-treated patients were primarily cardiovascular and gastrointestinal. Cardiovascular effects included tachycardia and increases in systolic and diastolic blood pressure. The differences between the intervention and control groups were small, and no differences were observed in discontinuation rates caused by adverse events. Nor were differences reported in growth and maturation between the intervention and control groups.
Adverse effects in the orlistat-treated patients were also low and similar in the intervention and control groups. Gastrointestinal effects were common. The number needed to harm (NNH) for fatty or oily stools was 2,4 and the NNH for fecal incontinence was 12.5
WHAT'S NEW: Clinicians treating obese kids have cause for optimism
Although the trials included in this review were heterogeneous and many were small, this systematic review provides evidence that intensive, comprehensive behavioral weight loss interventions for obese children can be effective up to 12 months after the conclusion of the program. Family physicians should consider referring obese children and adolescents to such programs—or finding ways to provide supportive strategies themselves.
Sibutramine and orlistat may be helpful in the context of comprehensive, intensive behavioral interventions, although there is no follow-up data to demonstrate long-term safety and weight maintenance after the medication is stopped.
CAVEATS: Little is known about long-term safety of the drugs
There have been few randomized trials of pharmacologic interventions in adolescents and none evaluating weight maintenance after 12 months (or discontinuation of treatment), or assessing long-term safety of the medication.
Sibutramine is not approved by the US Food and Drug Administration (FDA) for use in children or adolescents.7 Orlistat is currently approved only for individuals over the age of 12.8
In January 2010, an additional contraindication was added to the sibutramine drug label, stating that it is not to be used in patients with a history of cardiovascular disease.9 And the FDA is currently investigating a rare association between orlistat and liver injury, although no conclusions have been released.10 Children and adolescents are particularly vulnerable to long-term side effects, given their relatively young age at the time of drug initiation, so we urge caution with the use of these drugs in this patient population.
CHALLENGES TO IMPLEMENTATION: Intensive approach may be hard to reproduce
Implementation of high-intensity comprehensive interventions for obese children faces a number of roadblocks, including limited availability of programs, cost, and reimbursement. Most of the intensive interventions in these trials took place in specialty centers rather than in primary care offices. Replicating them could require a referral—or significant resources within the primary care setting itself. Yet many, if not most, insurance policies still do not cover such extensive lifestyle interventions. (For information on weight loss interventions for adults, see “Weight loss strategies that really work”).
None of these trials reported on cost or cost effectiveness. Despite the considerable cost of a comprehensive obesity management program, however, a successful weight-maintenance model could be a worthwhile investment in long-term health.
Lastly, the results of this trial should not negate the importance of obesity prevention efforts by parents, who are in the best position to reverse the childhood obesity epidemic.11
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999; awarded by the National Center for Research Resources; the grant is a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.