Lorcaserin hydrochloride for the treatment of obesity was a selective serotonin 2C receptor agonist designed to reduce appetite and support weight loss. Whilst it demonstrated efficacy in clinical trials and received approval in the United States, lorcaserin has never been authorised for use in the United Kingdom or European Union. In February 2020, the medication was voluntarily withdrawn from the US market following safety concerns about a potential increased cancer risk identified in long-term cardiovascular outcome studies. This article provides historical and clinical context about lorcaserin, its mechanism of action, evidence base, and the reasons for its withdrawal, alongside current UK-approved alternatives for obesity management.

What Is Lorcaserin HCl and How Does It Work for Weight Loss?

Lorcaserin hydrochloride is a selective serotonin 2C (5-HT2C) receptor agonist that was developed as a pharmacological treatment for obesity. The medication works by targeting specific receptors in the hypothalamus, the region of the brain responsible for regulating appetite and satiety. By selectively activating 5-HT2C receptors on pro-opiomelanocortin (POMC) neurones, lorcaserin promotes feelings of fullness and reduces food intake, thereby supporting weight reduction when combined with lifestyle modifications.

The selectivity of lorcaserin for the 5-HT2C receptor is clinically significant. Earlier weight-loss medications that affected multiple serotonin receptor subtypes, particularly 5-HT2B receptors, were associated with serious cardiac valvular disease. Lorcaserin was designed with approximately 15-fold selectivity for 5-HT2C over 5-HT2A receptors and higher selectivity over 5-HT2B receptors, theoretically reducing the risk of valvular heart disease that affected previous serotonergic agents. This selectivity profile was intended to minimise activation of 5-HT2B receptors on cardiac valves, which had been implicated in fenfluramine-related valvulopathy.

The mechanism of action involves modulation of the melanocortin system, which plays a central role in energy homeostasis. When 5-HT2C receptors are activated, they stimulate POMC neurones to release α-melanocyte-stimulating hormone (α-MSH), which then acts on melanocortin-4 receptors to decrease appetite. The primary effect in humans is appetite reduction and decreased food intake. This targeted approach distinguishes lorcaserin from other anti-obesity medications that work through different pathways, such as lipase inhibition or combined noradrenergic-serotonergic mechanisms.

Lorcaserin was intended for use as an adjunct to a reduced-calorie diet and increased physical activity in adults with obesity (BMI ≥30 kg/m²) or those who are overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidaemia. However, lorcaserin has never been authorised for use in the United Kingdom or European Union and was withdrawn from the US market in 2020 due to safety concerns.

Clinical Evidence for Lorcaserin in Obesity Management

The clinical efficacy of lorcaserin was evaluated in several large-scale, randomised controlled trials, most notably the BLOOM (Behavioural Modification and Lorcaserin for Overweight and Obesity Management) and BLOSSOM (Behavioural Modification and Lorcaserin Second Study for Obesity Management) trials. These phase 3 studies demonstrated statistically significant weight loss compared to placebo when lorcaserin was combined with lifestyle interventions.

In the BLOOM trial, which enrolled over 3,100 participants, those receiving lorcaserin 10 mg twice daily achieved a mean weight loss of 5.8% at one year compared to 2.2% in the placebo group. Approximately 47% of lorcaserin-treated patients achieved at least 5% weight loss (a clinically meaningful threshold) versus 20% of placebo recipients. The BLOSSOM trial, involving nearly 4,000 participants, produced similar results with 47.5% of lorcaserin patients achieving ≥5% weight loss compared to 20.3% on placebo.

The BLOOM-DM trial specifically examined lorcaserin in patients with type 2 diabetes, demonstrating not only weight reduction but also improvements in glycaemic control. Participants treated with lorcaserin experienced reductions in HbA1c levels alongside weight loss, suggesting potential metabolic benefits beyond simple weight reduction. However, patients with type 2 diabetes taking insulin or sulfonylureas experienced an increased risk of hypoglycaemia, requiring careful monitoring and potential dose adjustments of antidiabetic medications. Improvements were also observed in some cardiovascular risk factors including blood pressure in certain studies.

The long-term cardiovascular safety of lorcaserin was evaluated in the CAMELLIA-TIMI 61 trial, a large cardiovascular outcomes study involving over 12,000 patients. Whilst this trial demonstrated that lorcaserin did not increase major adverse cardiovascular events (MACE) compared to placebo, analysis revealed a statistically significant increase in cancer diagnoses among lorcaserin-treated patients (7.7% versus 7.1% over approximately 3.3 years). Cancers of the pancreas, colorectum, and lung were among those with numerical increases. In February 2020, the US Food and Drug Administration (FDA) requested voluntary withdrawal of lorcaserin from the market based on these findings, and the manufacturer complied, ceasing distribution globally.

Dosage, Administration and Treatment Duration

The following information is provided for historical reference only. Lorcaserin is not authorised in the UK and is no longer available for prescription anywhere globally.

When lorcaserin was available in the United States, the recommended dosage was 10 mg taken orally twice daily. The medication could be taken with or without food. An extended-release formulation (20 mg once daily) was also marketed. Unlike some weight-loss medications that require dose titration, lorcaserin was typically initiated at the therapeutic dose without a gradual increase.

US prescribing guidance recommended that healthcare professionals evaluate treatment response after 12 weeks of therapy. If a patient had not achieved at least 5% weight loss from baseline by this point, discontinuation of lorcaserin was advised, as continued treatment was unlikely to result in clinically meaningful weight reduction. This 12-week assessment point was specified in the US prescribing information.

For patients who did achieve adequate weight loss at 12 weeks, treatment could be continued as part of a comprehensive weight management programme. The clinical trials that established lorcaserin's efficacy typically extended for one to two years, though the optimal duration of treatment was not definitively established.

Dose adjustments were not routinely required for elderly patients or those with mild to moderate renal impairment. However, lorcaserin was not recommended for patients with end-stage renal disease or severe hepatic impairment due to limited safety data in these populations. The medication was contraindicated during pregnancy, and women of childbearing potential were advised to use effective contraception during treatment, as weight loss during pregnancy could pose risks to foetal development.

Side Effects and Safety Considerations

The adverse effect profile of lorcaserin in clinical trials included several side effects that occurred more frequently than with placebo. The most commonly reported adverse reactions included:

• Headache (reported in approximately 18% of patients)

• Dizziness (8–9% of patients)

• Nausea (9% of patients)

• Fatigue (7% of patients)

• Dry mouth (5% of patients)

• Constipation (6% of patients)

These effects were typically mild to moderate in severity and often diminished with continued use. However, they could impact treatment adherence and quality of life for some patients.

More serious safety concerns centred on serotonin syndrome, a potentially life-threatening condition that could occur if lorcaserin was combined with other serotonergic medications. Patients taking selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), triptans, or other serotonergic agents required careful monitoring. Symptoms of serotonin syndrome include agitation, hallucinations, rapid heart rate, fever, muscle rigidity, and gastrointestinal disturbances. Patients experiencing these symptoms required immediate medical attention and discontinuation of serotonergic medications.

Lorcaserin is a moderate inhibitor of the CYP2D6 enzyme, which could increase plasma concentrations of medicines metabolised by this pathway, including certain antidepressants (e.g., tricyclics), beta-blockers (e.g., metoprolol), antiarrhythmics, and dextromethorphan. Dose adjustments or additional monitoring may have been required when lorcaserin was co-administered with CYP2D6 substrates.

Cardiac valvulopathy was monitored closely in clinical trials given the history of fenfluramine-related valve disease. Echocardiographic assessments were performed in trials to evaluate valve function; however, routine echocardiography was not mandated in clinical practice. The incidence of FDA-defined valvulopathy was low and similar to placebo in most studies.

Hypoglycaemia was a concern in patients with type 2 diabetes, particularly those taking insulin or sulfonylureas. Dose reductions of antidiabetic medications were often necessary when initiating lorcaserin to reduce this risk.

Cognitive impairment, including attention and memory disturbances, was reported in some patients. Those experiencing significant cognitive effects, particularly if operating machinery or driving, were advised to exercise caution. Additionally, psychiatric adverse events including depression, anxiety, and suicidal ideation were monitored, though rates were generally similar to placebo.

The most significant safety concern that ultimately led to market withdrawal was the potential increased cancer risk identified in the CAMELLIA-TIMI 61 trial. Patients who had previously taken lorcaserin were advised to discuss ongoing cancer screening with their GP, following standard age-appropriate and risk-based screening protocols.

If you experience any side effects from any medication, you should report them via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk or search for MHRA Yellow Card in the Google Play or Apple App Store.

UK Regulatory Status and Prescribing Information

Lorcaserin has never been authorised for use in the United Kingdom by the Medicines and Healthcare products Regulatory Agency (MHRA) or the European Medicines Agency (EMA). Whilst the medication received approval from the US FDA in 2012 under the brand name Belviq, it did not gain marketing authorisation in Europe or the UK. The EMA's Committee for Medicinal Products for Human Use (CHMP) declined to recommend approval, citing concerns about the benefit-risk balance, particularly regarding potential cardiovascular and psychiatric risks.

Following the FDA's request for voluntary market withdrawal in February 2020 due to cancer safety signals identified in the CAMELLIA-TIMI 61 trial, lorcaserin was removed from the US market and is no longer available for prescription anywhere globally. The manufacturer, Eisai Inc., complied with the FDA's request and ceased distribution.

For UK healthcare professionals and patients, this means lorcaserin is not a treatment option for obesity management. Patients should not attempt to obtain lorcaserin from non-UK sources or online suppliers, as this poses regulatory and safety risks.

Current pharmacological options for weight management in the UK, as recommended by the National Institute for Health and Care Excellence (NICE), include:

• Orlistat (a lipase inhibitor available on NHS prescription for adults with BMI ≥28 kg/m² with associated risk factors or BMI ≥30 kg/m², per NICE CG189 and BNF guidance)

• Liraglutide 3.0 mg (a GLP-1 receptor agonist recommended by NICE TA664 for specialist weight management services in adults with BMI ≥35 kg/m² or ≥32.5 kg/m² in certain ethnic groups, with specific comorbidity and stopping rules)

• Semaglutide 2.4 mg (a GLP-1 receptor agonist recommended by NICE TA875 for specialist weight management services in adults with BMI ≥35 kg/m² or ≥32.5 kg/m² in certain ethnic groups, with specific comorbidity and stopping rules)

Naltrexone-bupropion combination is licensed in the UK but is not recommended for routine use by NICE.

Patients seeking weight management support should consult their GP or specialist weight management service to discuss appropriate, evidence-based interventions. NICE guidance (CG189) emphasises that pharmacological treatment should only be considered as part of a comprehensive approach including dietary modification, increased physical activity, and behavioural interventions. Any concerns about previous lorcaserin use obtained through non-UK sources should be discussed with a healthcare professional, particularly regarding appropriate cancer screening and ongoing health monitoring.

Frequently Asked Questions