Lorcaserin: an investigational serotonin 2C agonist for weight loss.

Abstract

PURPOSE:

The pharmacology, pharmacokinetics, and adverse effects of the selective serotonin (5-HT) agonist lorcaserin are reviewed, with an emphasis on efficacy and safety data from Phase III clinical trials.

SUMMARY:

Lorcaserin is highly selective for a subtype of 5-HT receptors important in appetite regulation, with low affinity for other 5-HT-receptor subtypes whose activation is thought to underlie serious cardiovascular adverse effects; such effects have been seen with nonselective serotonergic agents for weight loss (e.g., fenfluramine). In two Phase III trials of lorcaserin, the cumulative proportion of patients who achieved weight loss of ≥5% over 12 months was about 47% with lorcaserin use versus 20-25% among placebo users (p < 0.0001 for both trials). Lorcaserin was generally well tolerated in the clinical trials to date; nausea and vomiting, headache, and dizziness were the most commonly reported adverse effects. In two of the three Phase III trials to date, lorcaserin use was not found to increase the risk of cardiac valvulopathy; however, in the other Phase III trial, which focused on patients with diabetes, lorcaserin use was associated with an increased rate of new valvulopathy. In a carcinogenicity evaluation involving laboratory rats, lorcaserin was linked to the development of various malignancies, a finding with uncertain implications for its potential future use in humans.

CONCLUSION:

Lorcaserin, a 5-HT(2C) agonist, has demonstrated efficacy in patients who are obese or are overweight with associated comorbidities. Phase III trials have found that more than 35% of patients lost greater than 5% of their baseline weight. The maker of lorcaserin has indicated it will continue to seek U.S. marketing approval of the drug for the indications of long-term weight loss and weight-loss maintenance in specific patient populations.

• Authors: Kathryn M Hurren, Helen D Berlie
• Journal: American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists (Am J Health Syst Pharm) Vol. 68 Issue 21 Pg. 2029-37 (Nov 01 2011) ISSN: 1535-2900 [Electronic] England
• PMID: 22011982 (Publication Type: Journal Article, Review)

Chemical References

• Anti-Obesity Agents
• Benzazepines
• Receptor, Serotonin, 5-HT2C
• Serotonin 5-HT2 Receptor Agonists
• lorcaserin

Topics

• Animals
• Anti-Obesity Agents (adverse effects, pharmacology, therapeutic use)
• Benzazepines (adverse effects, pharmacology, therapeutic use)
• Clinical Trials, Phase III as Topic
• Humans
• Obesity (complications, drug therapy, physiopathology)
• Overweight (complications, drug therapy)
• Rats
• Receptor, Serotonin, 5-HT2C (drug effects, metabolism)
• Serotonin 5-HT2 Receptor Agonists (adverse effects, pharmacology, therapeutic use)
• Weight Loss (drug effects)