Anti-Obesity Medications: LorcaserinWednesday, October 2, 2013
The following is a summary of the findings from our recent systematic review of current literature published in Nature Endocrine Reviews, in which we discuss the efficacy and safety of new and emerging anti-obesity drugs.
We undertook a broad literature search of Medscape (PubMed) using “lorcaserin”, “naltrexone”, “bupropion”, “phentermine”, “topiramate” and “weight” or “obesity” as search terms. In addition, FDA Advisory Meeting Briefing Documents related to new drug applications for each agent were reviewed.
The first drug we discuss in our paper is lorcaserin, recently approved by the FDA and launched in the US under the trade name Beliviq.
Lorcaserin is a selective agonist of 5‑hydroxytryptamine receptor 2C (5-HT2C), which is predominantly expressed in hypothalamic pro opiomelanocortin (POMC)-producing neurons in the central nervous system – the very centre that controls hunger, appetite, satiety and other aspects of energy balance.
Activation of the 5‑HT2C receptors by lorcaserin stimulates the release of melanotropin‑α (also known as α‑MSH), which decreases appetite through stimulation of melanocortin receptor 4 (MC4‑R). Genetic variants of this receptor are widespread in the population and have been implicated in the development of obesity.
Importantly, lorcaserin has low affinity for other 5‑hydroxytryptamine receptor subtypes, such as 5-HT2B, which has previously been associated with the development of valvular heart disease in patients receiving serotonergic antiobesity drugs (like Fen-Phen).
The approval of lorcaserin by the FDA was based on the results of two phase II studies and three phase III randomized controlled trials involving well over 8,000 subjects. These studies included a large number of individuals with obesity related comorbidities like hypertension, cardiovascular disease, dyslipidaemia, impaired glucose metabolism, diabetes or sleep apnoea and each study is described in detail in our paper.
Although the average weight loss compared to the placebo group was relatively modest (on average about 3.5% more than the placebo group), almost twice as many participants in the lorcaserin group as in the placebo group lost at least 5% of their initial weight (47.5% versus 20.3%, respectively in one study).
These changes in body weight were accompanied by significant placebo-adjusted improvements in cardiometabolic risk factors and quality of life.
The reported rates of serious and nonserious adverse events were slightly higher in the active-treatment groups, the most common being headache (17% versus 10%), dizziness (9% versus 4%), nausea (8% versus 5%) and fatigue (7% versus 3%). No differences were observed between the groups in the occurrence of depression, anxiety or other psychiatric adverse events.
Particular attention was paid to the possibility of valvular disease by including echocardiographic assessments of all study participants, which did not reveal any significant difference in the incidence of new valvulopathies between the lorcaserin and placebo treated participants. Because new valvulopathies are a rather rare event, despite the thousands of participants in these studies, one cannot fully rule out a slightly increased risk, and this is an issue that deserves further attention.
Also with regard to safety, there is some suggestion that in extremely high doses in animal studies, lorcaserin may increase the risk of certain cancers, but there was no report of increased cancer risk in the clinical trials – again an issue that will need to be closely observed in future studies.
As with all new compounds, we still know little about long-term efficacy or safety of lorcaserin (at least when used longer than 24 months) – this, however, is not an unusual situation for new medications.
Obviously, as we point out in our review, the ultimate test of the usefulness of obesity drugs is not simply in terms of whether or not they help people lose weight (or keep it off) – the real test is whether or not they ultimately reduce obesity related health risks and improve quality of life – that question has yet to be answered for lorcaserin.
Disclaimer: lorcaserin is currently not approved for obesity treatment in Canada. I have received honoraria from the makers of lorcaserin (and other anti-obesity drugs) for consultation and research.
Rueda-Clausen CF, Padwal RS, & Sharma AM (2013). New pharmacological approaches for obesity management. Nature reviews. Endocrinology, 9 (8), 467-78 PMID: 23752772
Sunday, December 8, 2013
Phentermine works very well to suppress appetite, but caused an increase in my BPH symptoms. Can you tell me if lorcaserin and other appetite suppressing drugs also have this side effect?