The weight loss drug lorcaserin did not increase cardiovascular events based on findings from the CAMELLIA-TIMI 61 Trial presented Aug. 26 at ESC Congress 2018 and simultaneously published in the New England Journal of Medicine. The appetite suppressant is approved for use in the U.S. contingent on post-market studies assessing the risk of major cardiovascular events, but not in Europe.

The CAMELLIA-TIMI 61 Trial enrolled 12,000 adults from 473 centers in eight countries between January 2014 and November 2015. All participants had a minimum BMI of 27 kg/m and either established cardiovascular disease (with or without diabetes) or diabetes and at least one cardiovascular risk factor. Participants were randomly assigned (1:1 ratio) to lorcaserin (10 mg/twice a day) or placebo and followed for a median of 3.3 years.

Overall, the study met its primary safety endpoint of noninferiority of the drug compared to placebo for major adverse cardiovascular events (MACE). At study completion, MACE occurred in 6.1 percent of those taking lorcaserin and 6.2 percent of those on placebo. However, the trial did not meet its superiority endpoint for the composite of MACE plus hospitalization for unstable angina, heart failure, or any coronary revascularization (11.8 percent in lorcaserin group vs. 12.1 percent for placebo group).

Study investigators noted that those patients taking lorcaserin lost an average of 4.2 kg in the first year compared to 1.4 kg for those taking placebo. Additionally, 39 percent of those taking the drug had lost at least 5 percent of their body weight at one year compared with 17 percent of those in the placebo group. The differences between groups remained significant at 3.3 years of follow-up. Lorcaserin also appeared to reduce the conversion rate to diabetes in those patients with pre-diabetes at baseline, as well as lead to small improvements in levels of triglycerides, blood glucose, heart rate and blood pressure.

According to investigators, CAMELLIA-TIMI 61 is notable as it provides the first demonstration of cardiovascular safety of any weight loss agent in a dedicated cardiovascular outcomes trial. "We have been able to show for the first time that this weight loss drug does what it is intended to do. It helps people lose weight without causing an increase in MACE in a population at higher risk for heart attacks and strokes," said Erin Bohula, MD, an investigator with the trial. "One of our hypotheses was that losing weight with this medication might also lead to a cardiovascular benefit but we did not see that."

In a related editorial, Julie R. Ingelfinger, MD, and Clifford J. Rosen, MD, question whether the drug is an "elixir or liability." They caution that for now "the drug may be best used on a cautious basis according to the needs of individual patients" given its side effects and the need for more long-term data. Side effects included headache, fatigue, dizziness, diarrhea and nausea and were the reason for twice the number of discontinuations in the lorcaserin group compared with placebo, even though the total rates of discontinuation in both groups were similar.

Keywords: ESC18, ESC Congress, Primary Prevention, Secondary Prevention, Overweight, Obesity, Benzazepines, Myocardial Infarction

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