Patients administered the FDA-approved therapy reported tripled rates of weight-loss, along with noninferiority for risk of major cardiovascular events, over 1 year and an extension period.
Erin A. Bohula, MD
A selective receptor agonist that modulates appetite with proven benefit for weight management therapy has been shown to be safe and effective for cardiovascular indications.
In a new study including 12,00 overweight or obese patients with cardiovascular risks, selective serotonin 2C receptor agonist lorcaserin showed benefits as a weight-loss therapy without any increased risks for major cardiovascular risks versus placebo.
Lorcaserin was previously approved by the US Food and Drug Administration (FDA) as an adjunct therapy to reduced-calorie diet and increased physical activity for patients in need of long-term weight management. However, data on its long-term cardiovascular and metabolic safety is lacking. As worldwide obesity rates have nearly tripled in the past 4 decades, the discovery of an efficacious, safe weight-loss therapy with no added risk for major cardiovascular events is a crucial development.
The Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obsese Patients-Thrombolysis in Myocardial Infarction 61 (CAMELLIA-TIMI 61) study, presented at the European Society of Cardiology (ESC) 2018 Congress this weekend, sought a primary safety outcome of major cardiovascular events in patients administered either 10 mg twice daily lorcaserin or placebo.
Investigators—led by Erin A. Bohula, MD, of the Brigham and Women’s Hospital, Boston, MA—randomly assigned 12,000 overweight/obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to either treatment or placebo (n = 6000 each). Patients were required to have a body mass index (BMI) of at least 27, and reported a median BMI of 35. Median age in both treatment groups was 64 years, and the majority of patients were male (64.8% and 63.6%, respectively).
Patients were provided access to and were encouraged to participate in a weight-management program which included behavior therapy, dietary and exercise information, and telephone access to a dietitian.
The team sought a primary safety outcome of major cardiovascular events—as defined as either cardiovascular death, myocardial infarction, or stroke—as assessed at an interim analysis, in order to exclude a noninferiority boundary of 1.4.
If noninferiority was met, investigators assessed superiority in primary cardiovascular efficacy outcome (composite of major events, heart failure, hospitalization of unstable angina, or coronary revascularization) at the end of the trial.
After 1 year, the rate of patients to have lost at least 5% of their weight from baseline was more than double in the lorcaserin group (1986; 38.7%) than in the placebo group (883; 17.4%), giving investigators an odds ratio (OR) of 3.01 (95% CI; 2.74-3.30; P < .001). Patients treated with lorcaserin also reported improved blood pressure, heart rate, glycemic control, and lipid counts than patients administered placebo.
In the extended follow-up (median 3.3 years), the rate of the primary safety outcome was 2.0% annually in the lorcaserin group, and 2.1% annually in the placebo group, giving investigators a hazard ratio (HR) of 0.99 (95% CI; 0.85-1.14; P < .001). Respectively, the 2 groups reported extended major cardiovascular event rates of 4.1% and 4.2% annually (HR 0.97; 95% CI; 0.87-1.07; P = .55).
Adverse events were limited across both groups, with only serious hypoglycemia being reported a high rate of lorcaserin patients (13) than in placebo patients (4; P = .04).
Previous studies have shown that patients to receive lorcaserin had 3-4% greater weight loss than patients treated with placebo. The new trial results, showing lorcaserin plus lifestyle intervention result in net mean weight loss of 2.7% at 1 year, and more than tripled odds for weight loss of at least 5% or 10% versus patients given placebo.
Perhaps most impressively, the difference in weight loss was still significant through 40 months of follow-up.
“To put these findings in perspective, lifestyle interventions typically result in a weight loss of 2 to 10%,” investigators wrote. “The rate is 2 to 10% with pharmacotherapy and a more durable 15 to 60% with bariatric surgery.”
Investigators concluded that, along with maintaining its weight-loss capabilities in extended analysis, lorcaserin was able to meet FDA-mandated criteria for cardiovascular safety.
“Counterbalancing these serious safety concerns is the scope of the obesity epidemic,” investigators wrote. “Thus, the FDA has allowed approval of weight-loss agents contingent on the ability to rule out an increased risk of adverse cardiovascular outcomes in a dedicated postmarketing safety trial.”
The study, “Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients,” was published in New England Journal of Medicine on Sunday.