Efficacy and safety of lorcaserin in obesity: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT

Background: Lorcaserin is a novel, selective 5-hydroxytryptamine 2C serotonin receptor agonist, approved for the treatment of obesity. Several phase 3 randomized controlled trials (RCTs) trials have shown a significant reduction in body weight with lorcaserin.

Research design and methods: We systematically searched the database of PubMed, Embase, The Cochrane Library and ClinicalTrials.gov up to 31 July 2019 and retrieved all the studies conducted with lorcaserin for ≥1 year that have explicitly reported the efficacy and safety outcomes versus placebo. Subsequently, we studied the effect of lorcaserin on weight reduction, FDA-defined valvulopathy, depression and suicidal risks in RCTs.

Results: The meta-analysis of four RCTs (N = 16,856) demonstrated a significant decrease in body weight (mean ∆ −3.076 Kg; 95% CI, −3.49 to −2.66; P < 0.00001), compared to placebo. No significant difference in FDA-defined valvulopathy (RR 1.20; 95% CI, 0.89 to 1.63; P = 0.24), depression (RR 1.07; 95% CI, 0.80 to 1.43; P = 0.67) or suicidal risk (RR 1.43; 95% CI, 0.96 to 2.15; P = 0.08) has been observed with lorcaserin compared to placebo.

Conclusions: Lorcaserin reduces body weight modestly, with no obvious serious adverse side effects. The common adverse events noted with lorcaserin include nausea, dizziness, and transient headache.

KEYWORDS:

• Lorcaserin
• obesity
• anti-obesity drugs
• weight reduction
• neuropsychiatric manifestation
• valvulopathy

Article highlights

• Obesity poses a major public health risk, as it is frequently associated with significant increase in morbidity and mortality.

• Currently, five anti-obesity drugs have been approved by US FDA for long-term use including lorcaserin. Owing to its 15- to 90-fold selectivity to 5-HT_2c over 5-HT_2A and 5-HT_2B respectively, lorcaserin is posed to be devoid of (although biologically plausible) any significant increase in valvular heart disease (5-HT_2B) and neuropsychiatric symptoms (5-HT_2A), that have been seen with other non-selective 5-HT receptor agonists, such as fenfluramine and dexfenfluramine. Lorcaserin is a novel selective 5-HT_2c serotonin receptor agonist that has shown a significant reduction in weight, in various phase 3 RCTs without any significant untoward off-target side effects.

• Although obese patients responded well and exhibited a significant weight loss with lorcaserin, this seems to be a modest, at best. Moreover, a certain proportion of patients appeared to be non-responders to lorcaserin. Similarly, regain in weight after the initial 1 year of use was observed in certain percentage of subjects, despite the continued use of lorcaserin; nevertheless, the weight loss observed was still significantly better, with lorcaserin compared to placebo, at the second year.

• The Cardiovascular outcome trials (CAMELLIA TIMI 61) conducted with lorcaserin suggested no significant increase in the composite of cardiovascular risks. Additionally, lorcaserin use was associated with a significant decrease in future risk of incidental diabetes, microvascular complications (composite of renal outcomes including microalbuminuria) and also exhibited an increased chance of diabetes remission.

• Future trials that are currently underway will further explore the safety and efficacy of lorcaserin in the obese adolescent (12–17 years).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they were a previous investigator on clinical trials of Lorcaserin. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

Both AKS and RS were involved in the conception and design, or analysis and interpretation of the data; the drafting of the paper or revising it critically for intellectual content; and the final approval of the version to be published; and that all authors agree to be accountable for all aspects of the work.

Supplementary Material

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Additional information

Funding

This paper was not funded.