A new drug, lorcaserin, showed good weight loss results without the valvular side-effects associated with some other serotonin type agents in the Phase III Blossom (Behavioural Modification and Lorcaserin Second Study for Obesity Management) study, presented at the Obesity 2009 meeting held in October in Washington DC, USA.
Lorcaserin acts as an agonist at the 5HT2C-receptor. Lead investigator of the Blossom study, Dr Lee Kaplan (Massachusetts General Hospital, Boston, USA) explained that serotonin is known to be important in inducing weight loss; previous drugs have raised endogenous serotonin levels. More has been discovered about various different serotonin receptors, and it is now thought that the 5HT2B receptor is responsible for the cardiac valvular effects of these serotonergic drugs, while the 5HT2C receptor is responsible for weight loss. So by stimulating the 5HT2C receptor alone, it should be possible to induce weight loss without the valvular side effects.
In the BLOSSOM trial, 3,182 obese and overweight patients were randomised to treatment with lorcaserin 10 mg twice daily, 10 mg once daily, or placebo. After one year, the intention-to-treat analysis showed weight reductions of 5.8 kg in the lorcaserin twice daily group, 4.7 kg in the lorcaserin once daily group and 2.9 kg in the placebo group. When looking at only those patients who completed the study (about 60% of patients), weight reductions were larger —7.7 kg (lorcaserin twice daily), 6.5 kg (lorcaserin once daily), and 3.9 kg (placebo).
In the intention-to-treat analysis, 47.2% of patients in the lorcaserin twice daily group, lost more than 5% of their body weight, compared with 40.2% receiving lorcaserin once daily, and 25% of those on placebo. And weight reductions greater than 10% were achieved by 22.6% of the twice daily group and 17.4% of the once daily group.
The most common adverse events with lorcaserin were headache, nausea, dizziness, fatigue, and dry mouth. Approximately 100 patients reported a serious adverse event in the trial, but the difference between lorcaserin and placebo was not significant. Six events (including syncope, depression, and anxiety) were considered to be possibly related to the study drug.
The trial included 56 patients with pre-existing echocardiographic valvulopathy and there was no worsening of valve disease in these patients. Rates of new valve problems were similar in all three arms.