Belviq (lorcaserin) / Eisai, Ildong, TTY Biopharm, Pfizer - LARVOL DELTA

Long-term effects of weight-reducing drugs in people with hypertension. (PubMed, Cochrane Database Syst Rev) - "There have been multiple developments in the domain of medications for long-term weight reduction in recent years. Several pharmaceutical products have been removed from the market due to safety concerns, whilst new drugs have been introduced. Our critical outcomes of death and cardiovascular complications were not the focus of the trials included in this review but were sometimes presented as part of an 'adverse events' outcome, with the resultant data providing only very low certainty evidence. Overall, the evidence for people with hypertension remains insufficient to draw conclusions regarding the benefits of pharmacological weight loss in terms of reducing the risk of mortality or cardiovascular morbidity. Further trials are needed. Moreover, separate results for participants with hypertension should be made available from any completed trials involving both normotensive and hypertensive people."

Clinical • Journal • Review • Cardiovascular • Hypertension • Obesity

Mutagenicity of EAT-positive NDSRIs in HepaRG spheroids. (PubMed, NAM J) - "In this study, we investigated the genotoxicity and mutagenicity of six EAT-positive NDSRIs, N-nitroso-desmethyl-diphenhydramine, N-nitroso-duloxetine, N-nitroso-lorcaserin, N-nitroso-nortriptyline, N-nitroso-propranolol, and N-nitroso-sertraline, in 3D HepaRG spheroids using a 14-day treatment protocol...Quantitative analysis revealed varying levels of DNA damage and mutagenic potency among the six NDSRIs and two previously reported NDSRIs (N-nitroso-varenicline and N-nitroso-fluoxetine). These findings represent an important first step towards supporting the use of 3D HepaRG spheroids as a human-relevant in vitro new approach methodology (NAM) for mutagenicity assessment as a follow-up to the EAT. The results also provide evidence for genotoxic potency ranking of NDSRIs and offer mechanistic insights through mutational spectrum analysis."

Journal

Lorcaserin in Obesity: Identification of CNS Targets Using fMRI (clinicaltrials.gov) - P4 | N=40 | Active, not recruiting | Sponsor: Beth Israel Deaconess Medical Center | Trial completion date: Mar 2026 ➔ Jun 2027 | Trial primary completion date: Mar 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

Childhood Obesity, Medications, and Surgeries. (PubMed, Cardiol Rev) - "Epigenetic regulation, the unique gut microbiome role in contributing to obesity, environmental factors, and the social context of a child can precipitation of childhood obesity. In this review, we hope to explore the different medications for obesity, orlistat, glucagon-like peptide-1 agonists, liraglutide, semaglutide, exenatide, setmelanotide, metreleptin, naltrexone, lorcaserin, phentermine, metformin, fluoxetine, lisdexamfetamine, and zonisamide, while also reviewing surgeries such as the Roux-en-Y gastric bypass, laparoscopic or vertical sleeve gastrectomy, and adjustable gastric banding."

Journal • Cardiovascular • Gastrointestinal Disorder • Genetic Disorders • Obesity • Oncology • POMC-null Obesity • BDNF • IL6 • LEP • TNFA

Biomarkers of hypothalamic melanocortin activity in human energy balance. (PubMed, J Neuroendocrinol) - "Previous studies evaluated POMC concentrations in human CSF in relation to BMI and leptin and to weight loss, including pharmacotherapy with lorcaserin which targets POMC neurons, showing that lower baseline POMC predicted a better weight loss response to lorcaserin...However, the cohort with obesity contained subjects with very low CSF POMC levels that may indicate POMC deficiency and predict treatment response to melanocortin agonists. It remains to be determined if alternative biomarkers associated with low CSF POMC can be identified for use in the clinical setting."

Biomarker • Journal • CNS Disorders • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • POMC-null Obesity • LEP

Lorcaserin induces abdominal fat loss with associated improvements of the circulating metabolome/lipidome and no changes in the myostatin-activin-follistatin-IGF-1 axes: A 6-month long randomized placebo-controlled clinical trial. (PubMed, Diabetes Obes Metab) - "Lorcaserin treatment was associated with greater abdominal fat mass loss, favourable lipid profile changes, while MAFI components remained largely unaffected. Lorcaserin may improve cardiometabolic health primarily through reductions in central adiposity."

Clinical • Journal • Genetic Disorders • Obesity • IGF1

Towards next-generation 5-hydroxytryptamine 2C receptor modulators: Greener synthesis and evaluation of novel isocoumarin derivatives as PAAMs of 5-HT2CR. (PubMed, Bioorg Chem) - "The in vitro evaluation of synthesized compounds revealed that several of them functioned as selective 5-HT2CR agonists with additional PAAM (positive ago-allosteric modulator) properties (unlike Lorcaserin)...Thus, compound 3b emerged as a promising PAAM of 5-HT2CR for further preclinical assessments. 2009 Elsevier Ltd."

Journal

Psychosocial stress-induced cocaine seeking in rats is inversely correlated with activation of medial prefrontal cortical neurons projecting to the rostral periaqueductal gray (Neuroscience 2025) - "Grant Support NIH Grant R00DA039991; Grant Support Osteopathic Heritage Foundation Grant OHFE-E-2023-31 Cocaine Use Disorder is characterized by a high risk of relapse even after prolonged abstinence...Furthermore, we found significant negative correlations between psychosocial stress-induced cocaine seeking magnitude and the number of Fos-positive rPAGl/vl-projecting neurons within the prelimbic and anterior cingulate cortices. These findings suggest that the contributions of the rPAGl/vl to psychosocial stress-induced cocaine seeking may be modulated by top-down frontal cortical input."

Preclinical • CNS Disorders

Obesity in Menopause: New Horizons and Challenges in Pharmacologic and Surgical Treatment (OBESITY WEEK 2025) - "also proposed a clinical management algorithm for this population.A retrospective cohort (Hurtado et al., 2024) with 106 postmenopausal patients treated with semaglutide found greater weight loss in MHT users vs. non-users (9.9% vs. 6.7%, p = 0.012).A case-control study (Santini et al., 2022) showed that postmenopausal individuals undergoing Roux-en-Y gastric bypass had significantly greater fat mass reduction (–33.1% vs. –5.9%) and better lean mass preservation (57.7% vs. 52.5%, p = 0.001) than non-surgical controls.One pilot trial (Kapoor et al., 2023) assessed lorcaserin in overweight midlife individuals, reporting modest weight loss and improvement in vasomotor symptoms, suggesting a potential dual benefit.No randomized controlled trials were identified... Despite the clear metabolic impact of menopause, there is a notable lack of high-quality evidence guiding pharmacologic and surgical obesity treatment in this population. Preliminary findings support the use of..."

Genetic Disorders • Obesity

Cp 809101, a selective serotonin (5-ht)2c receptor agonist, attenuates the expression of methamphetamine preference in adolescent male and female rats. (Neuroscience 2025) - "Indeed, lorcaserin, a 5-HT2C receptor agonist, underwent clinical trials for the treatment of cocaine use disorder but failed and was later removed from the market by the FDA due to side effects. Preliminary results indicate that rats exhibit METH preference to the 0.5 mg dose of METH, and that the preference is attenuated with pretreatment with CP 80901. These results suggest that targeting the 5-HT2C receptor system with a more selective agonist is effective in reducing METH-seeking behavior in adolescent male and female rats, and adds to the preclinical data examining this receptor system in adult animals."

Preclinical • CNS Disorders • Psychiatry

The Effect of Serotonin 5-HT2C Receptor Modulation on Binge Drinking and Alcohol-Seeking in Female Mice. (PubMed, Addict Biol) - "These findings suggest that 5-HT2CR PAMs, at the tested doses, may lack intrinsic efficacy in modulating alcohol use. However, our lorcaserin data demonstrate that targeting 5-HT2CR remains a valid approach to reduce behaviours associated with AUD."

Journal • Preclinical • Addiction (Opioid and Alcohol)

Obesity Drugs Over the Past 20 Years: A Meta-Analysis of Clinical Trials using ML and AI (OBESITY WEEK 2025) - "GLP-1 receptor agonists such as liraglutide, semaglutide, and tirzepatide have emerged as the most effective treatments to date, achieving 10–22% weight loss in clinical trials. Novel multi-receptor agonists—including retatrutide (GLP-1/GIP/glucagon) and the investigational NA-931 (IGF-1/GLP-1/GIP/glucagon)—demonstrate even greater promise, with weight loss exceeding 24% and favorable safety profiles. In contrast, older agents such as sympathomimetics (phentermine), lipase inhibitors (orlistat), and withdrawn serotonergic drugs (lorcaserin) have shown moderate efficacy (5–15% weight loss) but are limited by tolerability and safety concerns... GLP-1 agonists outperform traditional agents in promoting sustained weight loss and metabolic improvements; however, they are associated with gastrointestinal side effects, high costs, and rare but serious risks (e.g., pancreatitis, thyroid tumors). Sympathomimetics raise cardiovascular concerns, while orlistat often results in poor..."

Retrospective data • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Pancreatic Cancer • Pancreatitis • Solid Tumor • Thyroid Gland Carcinoma • IGF1

Glucagon-Like Peptide-1 Receptor Agonists and Age-Related Macular Degeneration. (PubMed, JAMA Ophthalmol) - "Patients were prescribed either the GLP-1RAs liraglutide or semaglutide or OWLDs including lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion. In this cohort study, GLP-1RA use was associated with reduced risk of developing nonexudative AMD but was not associated with progression to exudative AMD among individuals with nonexudative AMD. These findings may inform future randomized trials evaluating the ocular effects of GLP-1RAs in nondiabetic populations."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Genetic Disorders • Macular Degeneration • Metabolic Disorders • Obesity • Ophthalmology • Retinal Disorders

Glucagon-like Peptide-1 Receptor Agonist Use and Risk of Cataract Development. (PubMed, Am J Ophthalmol) - "GLP-1RA use was associated with a significantly reduced risk of age-related cataract compared to OWLD use and no pharmacologic treatment. These findings support the need for randomized prospective trials and mechanistic studies to better understand this observed association."

Journal • Cataract • Genetic Disorders • Metabolic Disorders • Obesity • Ophthalmology

Rebalancing the Serotonergic System in Cocaine Dependence (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Mclean Hospital | N=10 ➔ 0 | Active, not recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal

Clinical factors associated with jawbone remineralization after nonsurgical treatment and imaging-based insights into its processes. (PubMed, Oral Radiol) - "Bone remineralization following jawbone destruction is influenced by patient-specific characteristics and treatment-related factors. Changes in CT values during bone remineralization and metabolic activity detected using PET/CT provide insights into the underlying processes of bone remineralization."

Journal • Oncology • Oral Cancer • Solid Tumor

Combination Lorcaserin and Betahistine Treatment Improves Cognitive Dysfunction and Dopaminergic Neuron Activity in a Rat Model of Diet-Induced Obesity. (PubMed, Brain Sci) - "Lorcaserin and betahistine co-treatment significantly increased the number of spontaneously active dopaminergic neurons of obese animals. These results demonstrate the potential of combination lorcaserin-betahistine treatment to reverse obesity-related cognitive deficits, possibly through enhancement of mesocortical dopaminergic neuron activity."

Journal • Preclinical • Cognitive Disorders • Genetic Disorders • Obesity

Serotonin 5-HT2C Receptor Signaling Analysis Reveals Psychedelic Biased Agonism. (PubMed, ACS Chem Neurosci) - "Despite earlier evidence of 5-HT2C G protein coupling promiscuity, the full signaling landscape remains incompletely characterized, which may help explain the limited efficacy and potential cancer risks associated with lorcaserin...Profiling of both 5-HT2C-selective and psychedelic ligands reveals diverse signaling profiles, with serotonergic psychedelics such as LSD and psilocin exhibiting a striking Gq/11 bias due to minimal secondary G protein activation. Altogether, this work provides a foundation for incorporating a broader view of 5-HT2C signaling modalities into future investigations of 5-HT2C drug development efforts."

Journal • CNS Disorders • Depression • Genetic Disorders • Obesity • Oncology • Psychiatry • ARRB1

Assessment of drug-related migraine in a real-world large-scale database. (PubMed, Front Pharmacol) - "The highest-risk agents included lorcaserin (BCPNN = 3.33), tasimelteon (3.20), and botulinum toxin type A (3.06). Given the public health burden of migraine, pharmacovigilance efforts should incorporate such findings to mitigate iatrogenic risks. Further prospective studies are warranted to establish causal mechanisms and optimize therapeutic decision-making."

Journal • Real-world evidence • CNS Disorders • Migraine • Pain

Stereoselective Nucleophilic Di- and Monofluoro(sulfoximidoyl)Methylation of C═C Bonds: Remote Neighboring Group Participation Enables Facile Access to Chiral γ-Fluorinated Amines. (PubMed, Angew Chem Int Ed Engl) - "The key features of this chemistry include 1) stereoselective addition of the difluoro(sulfoximidoyl)methyl anion to C═C bonds, although it was considered to be highly unfavorable from the view of hard-soft acid-base (HSAB) theory; 2) intriguing neighboring group participation of the oxygen from the nitro group that was found to play a crucial role in controlling the stereoselectivity and efficiency of the transformation and was supported by mechanistic experiments and DFT calculations. This method has been applied to the late-stage modification of several complex molecules and the preparation of enantioenriched bioactive γ-fluorinated amines, such as a phytopathogenic fungi inhibitor, TRPC6 and CDK11 inhibitors, and even monofluorinated lorcaserin, which further demonstrated the significance and potential of this approach."

Journal • CDK1 • TRPC6

Lorcaserin modulation of semantic drug cue-elicited effective brain connectivity in persons with cocaine and opioid use disorders. (PubMed, Psychiatry Res Neuroimaging) - "Our previous neuroimaging study showed that mirtazapine (a non-selective 5-HT2AR antagonist) can reduce the effective connectivity (EC) of the pathway from the anterior cingulate cortex (ACC) to the hippocampus. Notably, these EC outcomes remained unaffected by factors such as handedness, presence of drug metabolites in urine, pretreatment urine drug screen, and the type of substance used. This study contributes further evidence of serotonergic regulation of the ACC → hippocampus EC, and the potential for this EC to be an early signal of target engagement for medication to treat SUDs."

Journal • Addiction (Opioid and Alcohol) • Substance Abuse

Bariatric Surgery and Lorcarserin Administration Differentially Affect the Myostatin-Activin-Follistatin-Inhibin Axis: Results from Two Interventional Studies (ENDO 2025) - "Values < 0.00625 were considered significant due to multiple comparisons.In Study 1, Lorcaserin reduced body weight by 7.74% and fat mass by 8.46% (p: 0.03 ) at 6 months without affecting significantly lean mass or bone mass...Bariatric surgery resulted in more significant weight loss and metabolic outcomes and showed notable hormonal shifts in Myostatin and FSTL-3 (all p:<0.006). Further investigation into short and long-term effects of weight loss interventions not only on body weight and metabolic outcomes but also on muscle and bone changes as well as hormones regulating weight and lean mass loss are needed."

Bariatric surgery • Surgery • Genetic Disorders • Obesity • IGF1

Eating a high fat diet enhances sensitivity of rats to serotonin receptor agonists. (PubMed, Physiol Behav) - "These results suggest that nutritional factors impact drug sensitivity in ways that might be relevant for the therapeutic effectiveness and side effect severity of serotonergic drugs."

Journal • Preclinical • CNS Disorders • Depression • Genetic Disorders • Mood Disorders • Obesity • Psychiatry

G proteins of the G12 family expressed by POMC neurons regulate key metabolic functions. (PubMed, Sci Adv) - "Studies with G12/13 knockout mice showed that G12/13 signaling in POMC neurons mediated the beneficial metabolic effects of lorcaserin, an appetite-suppressant drug that selectively activates serotonin 5-HT2C receptors. These findings indicate that G12/13-coupled receptors expressed by POMC neurons represent potential targets for advanced classes of antidiabetic and appetite-suppressant drugs."

Journal • Obesity • POMC-null Obesity • LEP

Genotoxicity evaluation of ten nitrosamine drug substance-related impurities using 2D and 3D HepaRG cells. (PubMed, Regul Toxicol Pharmacol) - "After 24-h exposure, five EAT-positive NDSRIs, N-nitroso-duloxetine, N-nitroso-fluoxetine, N-nitroso-lorcaserin, N-nitroso-nortriptyline, and N-nitroso-varenicline, significantly induced DNA damage in both 2D and 3D models and increased MN and γH2A.X formation in 3D spheroids...The five EAT-negative NDSRIs, N-nitroso-diclofenac, N-nitroso-folic acid, N-nitroso-paroxetine, N-nitroso-desvaleryl-valsartan, and N-nitroso-desvaleryl-valsartan methyl ester, showed no DNA damage or MN formation in either model...Overall, the ten NDSRIs exhibited the same positive/negative genotoxicity outcomes in both the EAT and 3D HepaRG spheroids. These findings support the use of 3D HepaRG spheroids as an alternative in vitro model for detecting NDSRI-induced genotoxicity and confirming NDSRI responses in the EAT."

Journal