Obesity.(Drug Update)

Withdrawal of the popular obesity drugs fenfluramine and dexfenfluramine (Redux) from the U.S. market in 1997 left Americans hungry for new obesity drugs with long-term efficacy. They're still waiting, as their waistlines continue to grow.

In other words, there's no weight-loss drug now available that's close to ideal. Obesity plus overweight remains the most common nutritional disorder in the United States, with a prevalence that has ballooned by 75% since 1980. Available pharmacologic agents are rarely effective for weight loss or for improving obesity-related conditions unless they're used as part of a comprehensive approach that also includes dietary and lifestyle changes and behavioral therapy. Patients often regain weight after stopping treatment. But despite these shortcomings, some type of drug therapy is recommended for patients with a body mass index of 27 kg/[m.sup.2] or higher and obesity-related morbidity, and for everyone with a BMI of 30 kg/[m.sup.2] or higher.

Orlistat and sibutramine are the newest obesity drugs and are the only ones approved for long-term use. Both have been studied for at least 2 years. Along with behavioral interventions, these drugs are generally modestly effective for weight loss and maintenance, compared with placebo.

Behavioral interventions--which can be as simple as support group participation or consulting a registered dietitian--enhance the effects of treatment. In one study with 57 patients, loss of at least 15% of body weight was the benchmark for success. This goal was reached by 15% of patients treated with a drug only, 25% of those treated with a drug plus participation in a lifestyle intervention group, and 60% of patients who got the drug and participated in both lifestyle and behavioral intervention groups.

With the exception of orlistat, which is not absorbed into the systemic circulation, obesity drugs should be avoided by women who are pregnant or breast-feeding. A number of experts also don't prescribe orlistat during pregnancy.

Several other drugs are in development. Cannabinoid receptor blockers, now in phase III trials, may become the first approved appetite-reducing drugs that are not stimulants. Topiramate and other antiepileptics are being studied for obesity and may be particularly good for patients with bingeing disorders.

 
Drug             AWC/day*              Dosage 
 
LIPASE INHIBITOR 
orlistat         no generic available  120 mg b.i.d. 
 [Xenical]       [$2.76] 
 
MIXED NORADRENERGIC-SEROTONERGIC AGENT 
sibutramine      no generic available  5-15 mg/day 
 [Meridia]       [$4.16 (15 mg/day)] 
 
NORADRENERGIC AGENTS 
All agents in class are appetite suppressants. The four drugs listed 
here are on the DEA's schedule of controlled substances, so all are 
considered to have some potential for abuse. Few have been studied for 
longer than 6 months; all are approved for short-term use only (assumed 
to be less than 12 weeks). All are contraindicated in patients with 
moderate to severe hypertension, cardiovascular disease, or a history 
of drug abuse. 
phentermine      $1.02 (37.5 mg/day)   18.5-37.5 
 [Adipex-P]      [$1.67]               mg/day 
 [Atti-Plex P]   [$0.65] 
 [Pro-Fast SR]   [$0.89] 
benzphetamine    no generic available  25-50 mg/day 
 [Didrex]        [$1.07 (50 mg/day)] 
phendimetrazine  $0.36 (35 mg b.i.d.)  17.5-70 mg 
 [Bontril]       [$0.80]               b.i.d or t.i.d. 
 [Obezine]       [$0.10] 
 [Phendiet]      [$0.08] 
diethylpropion   $0.72                 25 mg t.i.d. 
 [Tenuate]       [$1.62] 
 
Drug             What the Experts Say** 
 
LIPASE INHIBITOR 
orlistat         Available in trade formulation only. The single Food 
 [Xenical]       and Drug Administration-approved obesity drug that 
                 works by blocking nutrient absorption. Inhibits 
                 pancreatic lipases, blocking absorption of about 
                 one-third of fat consumed. Approved for long-term use 
                 for weight loss and maintenance. Modestly effective; no 
                 abuse potential. Recently approved for use in 
                 adolescents. Taken during a fat-containing meal or 
                 within 1 hour after meal is over. Labeled dosage is 120 
                 mg t.i.d., but most use it b.i.d. with lunch and dinner 
                 and eat a low-fat breakfast. Mild to moderate 
                 gastrointestinal upset can occur if too much fat is 
                 consumed. GI effects can be ameliorated with a nightly 
                 dose of psyllium fiber, which binds to the oils that 
                 are not absorbed. A daily multivitamin can help 
                 counteract decreased absorption of fat-soluble 
                 vitamins. 
 
MIXED ...