Safety and Efficacy of Lorcaserin: A Combined Analysis of the BLOOM and BLOSSOM Trials

Aronne, Louis J.; Shanahan, William R.; Fain, Randi; Glicklich, Alan; Soliman, William; Li, Yuhan; Smith, Steven R.

doi:10.3810/pgm.2014.10.2817

Cited by 62 publications

(70 citation statements)

References 36 publications

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“…Lorcaserin elicits average weight loss of about 3.2 kg more than placebo (better than orlistat but still poor) and there are worries about its preclinical safety and psychiatric risks. There is no evidence that it increases valvulopathy [15], which was the main cause of the demise of the 5HT releasers and reuptake inhibitors fenfluramine and dexfenfluramine. This may remain a concern in the minds of some regulators, however.…”

Section: Disappointments Past and Presentmentioning

confidence: 99%

Horizons in the Pharmacotherapy of Obesity

Arch

2015

Curr Obes Rep

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Abstract:Obesity drugs have had a chequered history. In the recent past, only the low efficacy, pancreatic lipase inhibitor orlistat was available worldwide and it was little used. The 5HT2C agonist lorcaserin, and two combinations of old drugs have been approved in the United States but not in Europe. The diabetes drug liraglutide has been approved in both the US and Europe and seems likely to be most widely accepted. In view of regulators' caution in approving obesity drugs, some (like beloranib) may initially be progressed for niche obesity markets. New drug targets have been identified in brown adipose tissue with the aim of not only activating thermogenesis but also increasing the capacity for thermogenesis in this tissue. Attempts are being made to match the efficacy of bariatric surgery by mimicking multiple gut hormones. Unapproved pharmacotherapies are tempting for some patients. Others remain optimistic about more conventional routes to pharmacotherapy.3

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Section: Disappointments Past and Presentmentioning

confidence: 99%

Horizons in the Pharmacotherapy of Obesity

Arch

2015

Curr Obes Rep

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“…Overall effect size was modest (Kennett and Clifton 2010;Heal et al 2012, Bray andRyan 2014), with a 3.2 kg weight loss compared to placebo, approximating to a 3 % weight change. A meta-analysis of the BLOOM and BLOSSOM trials has been recently reported (Aronne et al 2014) and includes data from 6388 patients. By week 52, more than twice as many lorcaserin (10 mg b.i.d.…”

Section: Introductionmentioning

confidence: 99%

Lorcaserin and CP-809101 reduce motor impulsivity and reinstatement of food seeking behavior in male rats: Implications for understanding the anti-obesity property of 5-HT2C receptor agonists

Higgins

Silenieks²,

Altherr

et al. 2016

Psychopharmacology

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These results suggest that in addition to previously reported effects on satiety and reward, altered impulse control may represent a contributory factor to the anti-obesity property of 5-HT2C receptor agonists. Lorcaserin may promote weight loss by improving adherence to dietary regimens in individuals otherwise prone to relapse and may be beneficial in cases where obesity is associated with eating disorders tied to impulsive traits, such as binge eating disorder.

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“…In clinical studies, lorcaserin is well tolerated and decreases food intake and body weight (Smith et al, 2009(Smith et al, , 2010Chan et al, 2013;Aronne et al, 2014) at doses that have low potential for producing heart valve disease (Weissman et al, 2013) or abuse (Shram et al, 2011), effects commonly associated with 5-HT 2B and 5-HT 2A receptor agonists, respectively (Nichols, 2004;Hutcheson et al, 2011). In addition to preclinical studies demonstrating that lorcaserin decreases food intake and body weight (Smith et al, 2008;Thomsen et al, 2008;Higgins et al, 2013b;Grottick et al, 2015), lorcaserin is also shown to decrease nicotine selfadministration and the reinstatement of responding for nicotine in rats (Levin et al, 2011;Higgins et al, 2012Higgins et al, , 2013b.…”

Section: Introductionmentioning

confidence: 99%

Lorcaserin Reduces the Discriminative Stimulus and Reinforcing Effects of Cocaine in Rhesus Monkeys

Collins

Gerak

Javors

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Cocaine abuse and obesity are serious public health problems, and studies suggest that both dopamine and serotonin systems are involved in regulating the consumption of drugs and food. Lorcaserin has serotonin (5-HT) 2C receptor agonist actions, is approved by the U.S. Food and Drug Administration for treating obesity, and might be effective for treating cocaine abuse. These studies characterized the pharmacokinetic and behavioral profiles of lorcaserin (intragastric administration) and determined the effectiveness of lorcaserin to alter discriminative stimulus and reinforcing effects of cocaine (intravenous administration) in rhesus monkeys. Administered acutely, lorcaserin dosedependently increased the occurrence of yawning while decreasing spontaneous activity and operant responding for food. These effects appeared within 30-60 minutes of administration and began to dissipate by 240 minutes, a time course closely matching plasma concentrations of lorcaserin. In monkeys discriminating cocaine from saline, lorcaserin alone did not occasion cocaine-appropriate responding but shifted the cocaine dose-response curve to the right and down in two of three monkeys. When administered acutely, lorcaserin dosedependently decreased the rate at which monkeys responded for infusions of cocaine. When administered chronically, 3.2 mg/kg lorcaserin reduced the rate of cocaine-maintained responding by 50% for the duration of a 14-day treatment period. Together, these results show that lorcaserin attenuates the discriminative stimulus effects of cocaine after acute administration and the reinforcing effects of cocaine after acute and repeated administration, consistent with the view that it might have utility in treating cocaine abuse.

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Safety and Efficacy of Lorcaserin: A Combined Analysis of the BLOOM and BLOSSOM Trials

Cited by 62 publications

References 36 publications

Horizons in the Pharmacotherapy of Obesity

Horizons in the Pharmacotherapy of Obesity

Lorcaserin and CP-809101 reduce motor impulsivity and reinstatement of food seeking behavior in male rats: Implications for understanding the anti-obesity property of 5-HT2C receptor agonists

Lorcaserin Reduces the Discriminative Stimulus and Reinforcing Effects of Cocaine in Rhesus Monkeys

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