CAMELLIA–TIMI 61: Lorcaserin first weight-loss agent to show CV safety in high-risk patients

Lorcaserin has become the first weight-loss agent to show cardiovascular (CV) safety in patients at high CV risk, according to results of the CAMELLIA–TIMI 61 study presented at the European Society of Cardiology (ESC) Congress 2018.

“No weight-loss agents have convincingly demonstrated CV safety in a rigorous clinical study. Our present study supports the use of lorcaserin as an adjunct to lifestyle modification for long-term weight management in patients at high CV risk,” said investigator Dr Erin Bohula of the Brigham and Women’s Hospital, Boston, Massachusetts, US.

In the CAMELLIA–TIMI 61 (Cardiovascular and Metabolic Effects of Loraserin in Overweight and Obese Patients–Thrombolysis in Myocardial Infarction 61) study, designed to demonstrate CV safety for lorcaserin, 12,000 overweight or obese patients with atherosclerotic CV disease or multiple CV risk factors were randomized to receive either lorcaserin 10 mg twice daily or placebo. The primary safety outcome was major adverse CV events (MACEs) (a composite of CV death, MI, or stroke). The primary CV efficacy outcome was a composite of MACE, hospitalization for unstable angina, heart failure, or any coronary revascularization. [N Engl J Med 2018, doi: 10.1056/NEJMoa1808721]

After a median follow-up of 3.3 years, the rate of the primary safety outcome was 2.0 percent in the lorcaserin group vs 2.1 percent in the placebo group (hazard ratio [HR], 0.99; 95 percent confidence interval [CI], 0.85 to 1.14; p<0.001 for noninferiority). “The individual outcomes were generally consistent with the composite outcomes,” added Bohula.

However, the primary efficacy outcome failed to show superiority (12.8 percent vs 13.3 percent for lorcaserin vs placebo; HR, 0.97; 95 percent CI, 0.87 to 1.07; p=0.55 for superiority).

At 1 year, 38.7 percent of patients in the lorcaserin group and 17.4 percent in the placebo group achieved ≥5 percent weight loss (odds ratio, 3.01; 95 percent CI, 2.74 to 3.30; p<0.001). Compared with patients in the placebo group, those in the lorcaserin group had significant reductions in systolic blood pressure (difference, -0.9 mm Hg; 95 percent CI, -1.4 to -0.4; p=0.001), heart rate (difference, -1.0 bpm; 95 percent CI, -1.3 to -0.7; p<0.001), triglyceride levels (difference, -11.7 mg/dL; 95 percent CI, -14.7 to -8.7; p<0.001) and HbA_1c levels (difference, -0.2 percent; 95 percent CI, -0.3 to -0.2; p<0.001).

“Rates of serious adverse events were comparable between the two groups. More patients in the lorcaserin vs placebo group discontinued treatment due to dizziness [1.3 percent vs 0.3 percent], fatigue [1.1 percent vs 0.1 percent], headache [0.6 percent vs 0.3 percent] and nausea [0.6 percent vs 0.3 percent],” reported Bohula. “The rates of malignant neoplasm and 1-year US FDA-defined valvulopathy were similar in both groups.”

“The fact that lorcaserin demonstrated CV noninferiority but not superiority vs placebo is similar to what has been shown for dipeptidyl peptidase-4 inhibitors in general for the treatment of type 2 diabetes,” said discussant Professor Peter Nilsson of the Lund University, Lund, Sweden. “Nevertheless, lorcaserin has been shown to reduce nicotine dependence. The use of lorcaserin in obese smokers would be worth exploring.”