Lorcaserin

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Ujjwal Rastogi, M.B.B.S. [2]

Overview

Lorcaserin is a weight-loss drug developed by Arena Pharmaceuticals. It has serotonergic properties and acts as an anorectic. On 27 June 2012, the FDA officially approved lorcaserin for use in the treatment of obesity for adults with a BMI equal to or greater than 30 or adults with a BMI of 27 or greater who "have at least one weight-related health condition, such as high blood pressure, type 2 diabetes, or high cholesterol".

Mechanism of action

Lorcaserin is a selective 5-HT_2C receptor agonist and in vitro testing of the drug showed reasonable selectivity for 5-HT_2C over other related targets.

5-HT_2C receptors are located almost exclusively in the brain, and can also be found in the choroid plexus, cortex, hippocampus, cerebellum, amygdala, thalamus, and hypothalamus.

The activation of 5-HT_2C receptors in the hypothalamus is supposed to activate proopiomelanocortin (POMC) production and consequently promote weight loss through satiety. This hypothesis is supported by clinical trials and other studies.

Side effects

Lorcaserin was approximately as tolerable as placebo in Phase III, with 7% of participants in both the lorcaserin drug and placebo arms dropping out due to side effects.

The drug side effects compared with the placebo are listed in the following table:

Side effects	Placebo (%)	Drug arm (%)
Headache (most common)	11	18
Upper respiratory tract infection	11.9	14.8
Nasopharyngitis	12.0	13.4
Nausea	5.4	7.5

It was reported by national news-media that lorcaserin was associated with the development of cancer in laboratory rats.

Supportive trial data

BLOOM

[3]

BLOOM top line results were released on 30 March 2009. Measurements of efficacy using an intention to treat – last observation carried forward (ITT-LOCF), analysis showed that 47.5% of lorcaserin patients lost at least 5% of their body weight, compared to 20.3% for placebo.

BLOSSOM

BLOSSOM results were released on September 18, 2009. Measurements of efficacy using an intent-to-treat last observation carried forward, or ITT-LOCF, analysis showed that 47.2% of lorcaserin patients lost at least 5% of their body weight, compared to 25.0% for placebo. Lorcaserin patients achieved an average weight loss of 5.9%, or 12.7 pounds, compared to 2.8%, or 6.3 pounds, for placebo.