Side effects
The common side effects of lorcaserin include nausea, headache, dizziness, fatigue, dry mouth, cough,
constipation, hypoglycemia, and back pain.
3) Clinical efficacy
Lorcaserin was evaluated in the BLOOM (Behavioral Modification and Lorcaserin for Obesity and
Overweight Management) and BLOSSOM (Behavioral
Modification and Lorcaserin Second Study for Obesity
Management), randomized, double-blind, placebo-controlled phase III trials, which sought to investigate the
efficacy and safety of different doses of lorcaserin. In
the BLOOM study, 3,182 participants aged 18–65 with
a BMI ranging from 30–45 kg/m2
received either 10 mg
lorcaserin BID or placebo for 52 weeks [32]. At the end
of the trial, participants in the lorcaserin group continued the intake of lorcaserin at the same dose or placebo
for an additional 52 weeks. All patients were given diet
and exercise counseling. At the conclusion of the trial,
a weight loss greater than 10% was achieved in 22.6%
of participants in the lorcaserin group vs. 7.7% in the
placebo group.
Of the participants administered lorcaserin for an additional 52 weeks, 67.9% of those who
had an initial weight reduction >5% maintained this
loss compared to the 50.3% patients re-randomized to
receive placebo. In the BLOSSOM study, 4,008 patients
between 18–65 years of age with a BMI from 30–45
kg/m2
received either 10 mg QD or 10 mg BID of lorcaserin or placebo. After 52 weeks, significantly more
participants administered either 10 mg QD or 10 mg
BID of lorcaserin lost >10% of body weight (22.6% and
17.4%, respectively), compared to 9.7% in the placebo
group [33]. In a more recent RCT, 12,000 patients with
a BMI >27 kg/m2
and confirmed CVD in men >50 or
women >55 years of age were administered 10 mg BID
lorcaserin vs. placebo. This study primarily assessed the
cardiovascular safety and efficacy of this medication
after 1 year. Based on the findings, 14.6% of subjects in
the lorcaserin group had lost >10% weight compared to
4.8% of subjects in the placebo group who had a similar
CVD risk at the 3.3-year median follow-up [34]. Lorcaserin resulted in a weight loss of ~3.3% from the baseline
total body weight and improved fasting glucose, fasting
insulin, and hemoglobin A1c (HbA1c) levels. In a smaller cohort of the BLOOM-DM (Behavioral Modification
and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus) trial, which comprised 603
overweight or obese patients with T2DM and HbA1c
7.0% to 10.0%, a mean reduction in HbA1c was found
in the lorcaserin group compared to the placebo group
(0.9% vs. 0.4%) [35].
Due to the concerns regarding the
potential effect of lorcaserin on other types of 5-HT
receptors, which could thus affect valvular competency,
patients were monitored with serial echocardiograms
during these phase III trials. A pooled risk of 1.15 (95%
confidential interval=0.81–1.67) was found for the FDAdefined valvulopathy, suggesting that an unacceptable
increase in the risk of valvulopathy was not present
with the use of lorcaserin [36]. Although many longterm trials demonstrated beneficial effects of lorcaserin in T2DM and its substantial CVD safety profiles,
weight loss efficacy of lorcaserin is only modest.
3. Phentermine/topiramate
Phentermine/topiramate ER (Qysmia®
) was approved
by the FDA in 2012 as the first combination agent
for the long-term management of obesity. However,
the EMA has not approved this medication due to its
abuse potential, the lack of long-term data on the cardiovascular effects of phentermine, and the cognitive
side effects of topiramate—attention, language, and
memory impairment [27]. As this drug combination
contains phentermine, it is a controlled DEA schedule
IV substance.
1) Mechanism of action
This drug combination mainly suppresses appetite
through mechanisms that remain unclear. The central
sympathetic action of phentermine, a noradrenergic
agonist, is to enhance the release of norepinephrine,
dopamine, and serotonin [37]. Topiramate, a gammaaminobutyric acid agonist, glutamate antagonist, and
carbonic anhydrase inhibitor, was approved for the
treatment of epilepsy and prophylaxis of migraines
[38]. However, significant weight loss was observed
Young Jin Tak and Sang Yeoup Lee: An Updated Review on Anti-Obesity Drugs
www.wjmh.org 213
among epileptic patients treated with topiramate,
thereby leading to its evaluation in clinical studies for
the treatment of obesity. Although the actions of topiramate on the central nervous system have not been
completely understood, rodent studies have suggested
that it acts as a neurostabilizer and may boost thermogenesis [39,40]
