Lorcaserin was associated with significant weight loss among overweight and obese individuals without compromising cardiovascular safety, according to a large, randomized trial published Aug. 26 in The New England Journal of Medicine and presented at the European Society of Cardiology (ESC) Congress in Munich.
According to the authors, it is the first weight-loss drug to demonstrate cardiovascular safety in such a large-scale trial. Lorcaserin, an appetite suppressant, was approved by the FDA in 2012 on the basis that post-market safety studies would be conducted.
“We have been able to show for the first time that this weight-loss drug does what it is intended to do,” lead investigator Erin Bohula, MD, DPhil, with Brigham and Women’s Hospital in Boston, said in a press release. “It helps people lose weight without causing an increase in major adverse cardiovascular events in a population at higher risk for heart attacks and strokes.”
Bohula and colleagues randomized 12,000 patients with a body mass index (BMI) of 27 or higher to receive 10 mg of lorcaserin twice daily or a placebo. All participants had either atherosclerotic cardiovascular disease or multiple cardiovascular risk factors at baseline. Their median age was 64 years, 64.2 percent of participants were male and their median BMI was 35.
Patients in both groups were encouraged to participate in a weight management program, but those taking lorcaserin lost significantly more weight over the first year—9.3 pounds on average versus 3.1 pounds. At 40 months, the gap was slightly smaller (8.8 pounds versus 4.6 pounds) but remained statistically significant.
Notably, the weight-loss benefit didn’t come at the cost of excess cardiovascular risk—a problem seen with previous pharmacological approaches. About 2 percent of patients in both groups experienced an adverse cardiovascular event, defined as cardiovascular death, myocardial infarction or stroke.
When hospitalization for unstable angina, heart failure or any coronary revascularization were added to those outcomes, the rates remained similar between groups (4.1 percent per year for lorcaserin; 4.2 percent per year for placebo).
“One of our hypotheses was that losing weight with this medication might also lead to a cardiovascular benefit but we did not see that,” Bohula said. “While there were improvements in multiple cardiovascular risk factors, including weight, lipids and blood glucose, the magnitude of impact on these risk factors was relatively small.
“Nevertheless, the CAMELLIA-TIMI 61 study is notable as it provides the first demonstration of cardiovascular safety of any weight-loss agent in a dedicated cardiovascular outcomes trial.”
The authors suggesting keeping the weight off for a longer period of time may have more of an impact on cardiovascular risk.
The most common side effects attributed to lorcaserin were dizziness, fatigue, headache, diarrhea and nausea, which have been reported in previous trials. Hypoglycemia was also more common with the weight-loss agent than with placebo.
In a related editorial, Julie R. Ingelfinger, MD, and Clifford J. Rosen, MD, said the findings of an echocardiographic substudy should be followed further. In 3,270 patients for whom the echocardiographic data were available, 1.8 percent of those in the lorcaserin group and 1.3 percent of those in the placebo group showed new or worsening heart valve disease. Also, new or worsening pulmonary hypertension was present in 1.6 percent of patients receiving the drug and 1.0 percent of those on placebo medication.
“It would appear that long-term data remain very important with regard to cardiovascular safety, given that the use of lorcaserin is likely to extend for years to maintain weight loss,” the editorialists wrote.
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.