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modification, have been established through Lorcaserin for Obesity and Overweight Management
prospective randomized, controlled trials. Response in Diabetes Mellitus (BLOOM-DM) study was a
rates vary among the studies, participants assigned randomized, double-blind, placebo-controlled trial
to the medication groups achieved significantly that evaluated the efficacy and safety of lorcaserin
greater weight loss than compared to placebo, as (administered in conjunction with a lifestyle
well as improvements in cardio metabolic risk factors modification program) for weight loss among those
and quality of life. The average weight loss ranged with type 2 diabetes showed almost similar results
from 7.0 to 12.4% among participants who completed Rates of adverse events (AEs) and discontinuations
1 year of treatment, who received one of the four due to AEs in both trials were generally low (6–7%),
newer medications groups, as compared to 1.6 to with the most common side effect being headaches
3.5% among those who received placebo.
(6,8); however, around a third of patients in total
withdrew from one trial, and in the other trial
Lorcaserin the proportion of withdrawals rose to over 40%.
Lorcaserin, was first of these, approved in 2012, Lor- Echocardiogram studies were performed on all phase
caserin is selective 5-hydroxytryptamine 2C (5-HT2C) III trial participants, leading to the final assessment
receptor agonist to cause the release of serotonin (5- that lorcaserin did not cause cardiac valve tissue
HT) and inhibit the subsequent uptake of serotonin fibrosis.
(6). Anorectic POMC neurons expressing 5-HT2CR
depolarize on receptor activation and release MSH, Phentermine/Extended-Release Topiramate
which activate MC4R expressing neurons, principally Combination of phentermine and extended-release
within the Paraventricular nucleus [PVH] of hypothal- (ER) topiramate has been developed, approved by
amus.
the FDA for weight loss in 2012. Exact mechanism
It has low specificity for the 5-HT2B receptor (~100 of action remains unknown, phentermine is believed
times lower than that of the 5-HT2C receptor) (6), to mediate the release of catecholamines (including
lorcaserin carries a low risk of causing heart-valve noradrenaline and dopamine) in the hypothalamus,
abnormalities with long-term use. Side effects of which blunts appetite, while topiramate strengthens
lorcaserin are neuroleptic malignant syndrome-like the activity of the neurotransmitter gamma-
reactions: headache, dizziness, fatigue, nausea; dry aminobutyrate, [GABA] modulates voltage-gated
mouth; constipation and in diabetic patients cause ion channels, and inhibits AMPA/kainite excitatory
hypo glycaemia, and fatigue. glutamate receptors and carbonic anhydrase, which
prolongs satiety.
The first study investigating lorcaserin, the Behavioral
Modification and Lorcaserin for Overweight and Obe- Although originally declined for approval due to
sity Management (BLOOM) study, enrolled people 18 concerns over the increased risk of depression and
to 65 years of age [mean baseline weight of ~100 kg, cognitive-related disorders, as well as cardiovascular
] with a baseline BMI of 30 to 45 kg/m2 or a BMI of events, the drug was reconsidered and approved
27 to 45 kg/m2 with at least 1 concomitant weight-re- by the FDA for weight loss in 2012. Side effects
lated comorbidity. A total of 3182 participants were reported by the FDA include tingling of hands and
randomized to receive lorcaserin 10 mg twice a day feet (paraesthesia), dizziness, altered taste sensation,
(n =1595) or placebo (n =1587) for 52 weeks. insomnia, constipation and dry mouth.
Patients in the lorcaserin group lost an average of Clinical trials which played key role in is approval
5.81±0.16% of the baseline body weight, as compared include EQUATE, CONQUER, EQUIP and SEQUEL.
with 2.16±0.14% in the placebo group (P<0.001) The EQUATE trial, a 28-week, RCT, phase III study,
More patients lost 10% or more of their baseline compared the combination treatment of phentermine/
body weight in the lorcaserin group (22.6%) than topiramate (high and low dose) with the individual
in the placebo group (7.7%,P<0.001). patients who components alone (both high- and low-dose
achieved 5% weight loss of baseline weight after phentermine and high- and low-dose topiramate).
52weeks, seen in 47.5% of those receiving lorcaserin Weight loss was significantly greater in patients
compared with 20.3% receiving placebo and the loss receiving the high-dose combination treatment
was maintained in a greater proportion of patients compared with high doses of both compounds alone.
who continued to receive lorcaserin in year 2 than in
those who were reassigned to receive placebo (67.9% CONQUER was a 56-week, RCT double-blind, placebo-
vs. 50.3%,P<0.001). The Behavioral Modification and controlled, phase III trial in which two phentermine/

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