Safety and efficacy of fenproporex for obesity treatment: a systematic review

Abstract

OBJECTIVE To evaluate clinical evidence on the safety and efficacy of fenproporex for treating obesity.METHODS MEDLINE, LILACS and Cochrane Controlled Trials Register were searched as well as references cited by articles and relevant documents. Two authors independently assessed the studies for inclusion and regarding risk of bias, collected data, and accuracy. Eligible studies were all those placebo-controlled that provided data on the efficacy and safety of Fenproporex to treat obesity.RESULTS Only four controlled studies met the inclusion criteria. One randomized, placebo-controlled trial on Fenproporex was found on electronic databases. Three placebo-controlled studies (in non-indexed journals) were identified by hand-searching. Patients with cardiovascular and other comorbidities were excluded in all studies. Trials lasted from 40 to 364 days and doses ranged from 20 to 33.6 mg/d. All controlled studies found that weight loss among Fenproporex-treated patients was greater than that produced by the placebo, but drug effect was modest. Fenproporex produced additional weight reductions of 4.7 kg (one year), 3.8 kg (six months) and 1.55 kg (two months) in average, in relation to diet and exercise only (three trials). Insomnia, irritability, and anxiety were the most frequently reported side effects in the four studies.CONCLUSIONS There is a paucity of randomized, placebo-controlled trials on Fenproporex and those identified here present major methodological flaws. These studies suggest that Fenproporex is modestly effective in promoting weight loss. Nonetheless, they failed to provide evidence that it reduces obesity-associated morbidity and mortality. Data from these studies are insufficient to determine the risk-benefit profile of Fenproporex. Abuse potential and amphetamine-like adverse effects are causes for concern.

Teratogen update: Amphetamines

“…None of these drugs are marketed for the treatment of ADHD. Fenproporex, a compound with structural similarity to amphetamine and prescribed as an anorectic drug, is 60-80% converted to amphetamine in rats and humans (see review by Paumgartten, Pereira, & de Oliveira, 2016). While data on fenproporex could be considered relevant to the possible developmental effects of amphetamine, we did not locate adequate studies on human pregnancy outcomes after fenproporex exposure.…”

Possible Mechanisms Involved in the Vasorelaxant Effect Produced by Anorexigenic Drugs in Rat Aortic Rings

“…The maximal plasmatic concentration of fenproporex occurs 2–4 h post-administration and its effect lasts for 6–8 h. It has renal clearance and eliminates fully after 48 h [2,7,21,22]. Among the adverse events are glaucoma, pulmonary artery hypertension, vomiting, headaches, vertigo, tachycardia and insomnia [19].…”

The return of amphetamine-like anorectics: a backward step in the practice of evidence-based medicine in Brazil

“…A recent systematic review found only four controlled trials of fenproporex, which had in common a flawed study design with a high risk of selection, performance, and detection biases as well as incomplete outcome data 6 . Another systematic review of clinical trials of amfepramone, fenproporex, and mazindol revealed that 19 out of 25 studies included in the review showed a high risk of bias and authors' conclusion was that these drugs "…showed poor evidence of efficacy in the treatment of overweight and obese patients" 7 (p. 317).…”

“…Besides being a risk factor for cardiovascular morbidity, amphetamines are psychostimulant drugs and may induce sleeplessness, mood changes, and psychiatric disorders. Several cases of abuse and dependence to fenproporex (converted into amphetamine in the body) were reported 6 .…”