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Pharmacological Management of the Patient with Obesity
Published in James M. Rippe, Lifestyle Medicine, 2019
Magdalena Pasarica, Nikhil V. Dhurandhar
Lorcaserin is a selective serotonin receptor agonist influencing hunger.41 A 12-week weight loss study used different doses of lorcaserin vs. a placebo in 469 adults. Compared to the placebo group, there was more weight loss in the lorcaserin groups proportionate to the dose. Side effects included headache, dizziness, and nausea.42In a one-year lorcaserin study, 4,008 adults with obesity and overweight received either lorcaserin 10 mg once or twice daily. All subjects received a lifestyle intervention program. Weight loss (in the 5%–10% range) was statistically significant in the lorcaserin group compared to the placebo group and was dose-dependent. No increase in valvulopathy was seen in serial echocardiograms.43
Pharmacotherapy for Weight Loss
Published in Ruth B.S. Harris, Appetite and Food Intake, 2017
In rats, a single oral dose of lorcaserin decreased eating during the first 2 hours, with the effect maintained over the following 22 hours (Smith et al., 2008), and a 4-week trial of locaserin in diet-obese rats resulted in reduced food intake and a selective loss of fat mass (Thomsen et al., 2008). Tests with selective 5-HT receptor subtype antagonists indicated that lorcaserin’s eating-inhibitory effect depends on 5-HT2C receptors (Thomsen et al., 2008). In humans, the efficacy and safety of lorcaserin were evaluated in three separate phase III trials (Table 13.2). Lorcaserin produced only modest weight loss, as summarized in a recent meta-analysis taking into account five randomized controlled studies, with a mean weight loss of 3.2 kg at 1 year and body mass index reduction of 1.2 kg/m2 compared with placebo (Chan et al., 2013).
Current research and future hope
Published in G. Michael Steelman, Eric C. Westman, Obesity, 2016
Greenway Frank L., R. Smith Steven
Lorcaserin is a serotonin agonist specific to the serotonin 5-hydroxytryptamine (5-HT) 2C receptor. Fenfluramine was a nonspecific agonist of this receptor that is metabolized to nor-dexfenfluramine, which has a greater affinity for the 5-HT2B receptor, the receptor associated with heart valve pathology, than serotonin itself (74). Thus, lorcaserin has the potential to replace fenfluramine in the phentermine/fenfluramine combination without the risk of heart valve pathology. Lorcaserin was approved for the treatment of obesity in 2012 and gives 3.6 kg greater weight loss than a placebo (75). A clinical trial testing the efficacy and safety of the lorcaserin/phentermine combination for the treatment of obesity is presently in progress (76).
Biochanin A attenuates obesity cardiomyopathy in rats by inhibiting oxidative stress and inflammation through the Nrf-2 pathway
Published in Archives of Physiology and Biochemistry, 2023
Jansy Isabella Rani A, V. V. Sathibabu Uddandrao, Sangeethadevi G, Saravanan G, Chandrasekaran P, Sengottuvelu S, Tamilmani P, Sethumathi P P, S. Vadivukkarasi
Normal diet was prepared according to AIN-93 guidelines with all the recommended macro and micronutrients (Brahma Naidu et al. 2016) in sterile condition and fed to the Group I (Normal control) with water, ad libitum. HFD composition was prepared as described by Sathibabu Uddandrao et al. (2019) prepared at NIN (National Institute of Nutrition), Hyderabad, India, as per nutrition guidelines. Obese groups (Group-II to Group-IV) initially were fed with HFD for 15 weeks to induce the obesity (20 g daily) then the HFD rats supplemented with BCA (Group III) and Lorcaserin (Group IV) for the period of 30 days with respective doses once per day. Lorcaserin, a well-known anti-obesity drug, facilitated sustained weight loss without increasing the rate of major cardiovascular events in a high-risk population of overweight or obese patients (Bohula et al. 2018). Thus, the therapeutic effect of BCA was compared with lorcaserin.
Efficacy and safety of lorcaserin in obesity: a systematic review and meta-analysis of randomized controlled trials
Published in Expert Review of Clinical Pharmacology, 2020
Awadhesh Kumar Singh, Ritu Singh
The reason for initial rejection of lorcaserin by FDA in 2010 was based on – a. the difference in mean weight loss versus placebo was about 3% and thus did not satisfy the first ‘mean’ efficacy criteria (placebo-subtracted weight loss ≥5% at 1 year), although lorcaserin did fulfill ‘categorical’ efficacy criteria (≥35% patients loosing ≥5% of body weight in the active arm, approximately double the proportion achieved by placebo), b. concern related with increase in mammary and brain tumors in preclinical studies [11]. However, FDA re-review in 2012, approved lorcaserin with a mandated cardiovascular outcome trial. FDA review also found no significant increase in FDA-defined valvulopathy or FDA-defined VHD (defined as mild or greater aortic regurgitation [AR] and/or moderate or greater mitral regurgitation [MR]) or neuropsychiatric symptoms (depression or suicidal risk) with lorcaserin. The most common adverse events noted with lorcaserin include nausea, dizziness and transient headache [12].
Pharmacotherapy in obesity: a systematic review and meta-analysis of randomized controlled trials of anti-obesity drugs
Published in Expert Review of Clinical Pharmacology, 2020
Awadhesh Kumar Singh, Ritu Singh
Nausea, headache, and dizziness were the most common and consistent side effects observed with lorcaserin in all RCTs. No significant increase in FDA-defined valvulopathy, depression and suicidal risk was observed with lorcaserin in any of phase 3/4 studies, unlike other nonselective serotonin receptor agonists [26–29]. Interestingly, a meta-analysis by DiNicolantonio and colleague (based on 3 RCTs) reported a significant increase in the FDA-defined moderate or greater MR (RR 1.88; 95% CI, 1.02 to 3.47; P = 0.04) and depression (RR 1.89; 95% CI, 1.04 to 3.44; P = 0.04) with lorcaserin [59]. The medical review by FDA (based on 3 RCTs) found an increased risk of FDA-defined moderate or greater MR (RR 1.95; 95% CI, 1.05 to 3.59; P = not reported) mITT-LOCF analysis data, but not in completers group analysis. However, no significant increase in the FDA-defined valvulopathy (RR 1.16; 95% CI, 0.81 to 1.67, P = not reported) or the FDA-defined mild or greater AR (RR 0.89; 95% CI, 0.56 to 1.42; P = not reported) was observed with lorcaserin [60]. Lorcaserin should not be used concomitantly with other selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors so as to avoid hyper-serotonergic/neurolept-malignant syndrome [61].