Side effects The common side effects of lorcaserin include nausea, headache, dizziness, fatigue, dry mouth, cough, constipation, hypoglycem...
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]
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