Lorcaserin proven safe as weight loss agent in obese patients CAMELLIA-TIMI 61 trial: Results from ESC 2018, Munich

The selective serotonin 2c receptor agonist, Lorcaserin has been proven to be effective in the promotion of sustained weight loss through appetite suppression in obese and overweight patients, with no increase in cardiovascular events, according to the CAMELLIA-TIMI 61 (Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients–Thrombolysis in Myocardial Infarction 61) trial, presented at the ESC conference in Munich.

Over 40 % of adults are obese in the US. Although, lifestyle modification such as diet, exercise and behavior changes remain the mainstay of therapy, other surgical and medical options such as bariatric surgery and drug therapy may also be considered. Weight loss may be challenging due to increased rates of adverse cardiovascular events, frequently seen with drugs such as dexfenfluramine, fenfluramine, and sibutramine. In this randomized trial,12,000 obese and overweight enrollees (body mass index [BMI] >27 kg/m²), with established atherosclerotic cardiovascular disease or multiple cardiovascular risk factors,  were randomized to 10mg twice daily of the selective serotonin 2C receptor agonist Lorcaserin, versus placebo to assess cardiovascular safety and efficacy in obese and overweight patients. The follow-up duration was 3.3 years.

The principal safety outcome measured was major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke), whereas the primary cardiovascular efficacy outcome was extended major cardiovascular events (a composite of major cardiovascular events plus heart failure, hospitalization for unstable angina, or coronary revascularization).

In the study, Bohula et al. report weight loss of ≥ 5% occurred in 38.7% versus 17.4% in the lorcaserin and placebo groups respectively. Moreover, the primary safety outcome occurred in 2% per year versus 2.1% per year in the in the Lorcaserin and placebo groups respectively (p for noninferiority <0.001). As the condition for noninferiority was met, further analyses were performed focussing on superiority testing for cardiovascular efficacy. Extended major adverse cardiovascular events occurred in 4.1% per year versus 4.2 % per year in the Lorcaserin and placebo groups respectively, so the p-value was not significant for efficacy.

This trial confirmed the safety of Lorcaserin as compared with placebo among obese and overweight patients with cardiovascular disease. At the same time, Lorcaserin was associated with a significant weight reduction, with no increase in adverse cardiovascular events at a median of 3.3 years.

This drug represents an addition to the currently available options for weight loss including lifestyle modification and bariatric surgery. Speaking of the role of this drug in the treatment of overweight or obese patients, Dr. Julie R. Ingelfinger commented in an accompanying editorial, “Will lorcaserin prove to be helpful over the long haul? For now, the drug may be best used on a cautious basis according to the needs of individual patients. As in other reports on its use, the side effects of a headache, fatigue, dizziness, diarrhea, and nausea led to twice the number of discontinuations in the lorcaserin group as in the placebo group, although the total rates of discontinuation were similar in the two groups. With respect to efficacy, liraglutide would provide a similar degree of weight loss but a lower risk of diabetes.” When asked about the future in this field, Dr. Erin Bohula, the primary investigator stated, “There is a huge demand for a tool to treat obesity. There is a gap between bariatric surgery and lifestyle changes. So, there’s a lot of interest in having other tools, other pharmacologic agents and so I hope there will soon be other safe and effective options.”