A Risk-Benefit Assessment of Anti-Obesity Drugs

Abstract

This review evaluates the benefits and potential health risks of the currently used drugs that are approved for the pharmacological treatment of obesity. Analysis of several long term clinical trials indicates that all of these drugs are efficient in reducing excess bodyweight, and that the majority of them allow the maintenance of the reduced bodyweight for at least 1 year. However, the loss of bodyweight attributable to these drugs is in general rather modest, approaching only 0.2 kg per week during the first 6 months of treatment, and at least a partial regain of bodyweight occurs when these drugs are used for periods longer than 1 year. All of these drugs induce several adverse effects. Although most of these adverse effects are mild and transient, the prolonged use of adrenergic or serotonergic anorectic drugs, or their use as combination treatment, may induce serious and potentially life-threatening complications, such as primary pulmonary hypertension or valvular heart disease. The adrenergic appetite-suppressing drugs are not recommended for the treatment of obesity, since their safety has never been evaluated in long term clinical trials, and because of their stimulatory effects on the cardiovascular and nervous systems. The serotonergic drugs, such as fenfluramine and dexfenfluramine, have been the most widely used during the past decade; however, both these compounds have recently been withdrawn from the market, since their use was associated with serious cardiovascular complications. The safety of the prolonged therapeutic use of newer compounds such as sibutramine and orlistat has not yet been demonstrated. Therefore, none of the currently available anti-obesity medications meets the criteria of an 'ideal anti-obesity drug' and, if prescribed, these medications should be used with caution and only under careful medical supervision. Since obesity is recognised as a chronic health-threatening condition, and since classical behavioural therapeutic approaches lack long term efficacy, there is clearly a need for an efficient pharmacological treatment offering an acceptable safety profile. Such a treatment is not available at present. Development of new agents and a more careful assessment of the safety of currently available drugs are needed.

Identification of Acyl Coenzyme A:Monoacylglycerol Acyltransferase 3, an Intestinal Specific Enzyme Implicated in Dietary Fat Absorption

“…However, the mechanism for Orlistat, which is to inhibit pancreatic lipase, leads to the undesirable side effect of fecal leakage (15). An alternative approach may be to allow for the digestion of fat to fatty acids in the gut but block the uptake or the packaging of fatty acids into chylomicron particles.…”

Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference

“…[158][159][160][161][162] Appetite-suppressing agents have lost favor due to their side effects. 163 Recent data suggest a role for orlistat, a lipase inhibitor, as an adjunct to weight loss. 164 Several studies have reported beneficial effects of bariatric surgery, [165][166][167] although precipitous weight loss has the potential to exacerbate steatohepatitis.…”

An update on the pharmacological treatment of obesity

“…However, these medications were found to have multiple, potentially fatal side effects, or a potential for abuse, which resulted in either their withdrawal from the market, or to the implementation of regulations prohibiting their use in the treatment of obesity 21,22 . The most recent prescription anti-obesity medications to be removed from the market were fenfluramine and its isomer dexfenfluramine.…”