medwireNews: The weight-loss medication lorcaserin neither increases nor reduces cardiovascular risk, report the CAMELLIA–TIMI 61 investigators.
During a median 3.3 years of treatment, the primary cardiovascular safety endpoint of cardiovascular death, myocardial infarction, or stroke occurred at a rate of 2.0% per year in the 6000 participants randomly assigned to take lorcaserin 10 mg twice/day.
The corresponding rate among the 6000 patients who took placebo was 2.1%, making lorcaserin statistically noninferior to placebo, Erin Bohula (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and study co-authors report in The New England Journal of Medicine.
But the superiority endpoint, adding in heart failure, hospitalization for unstable angina, and coronary revascularization, was not met; the annual endpoint rates were 4.1% and 4.2% per year for patients taking lorcaserin and placebo, respectively.
Three-quarters of the trial participants had established atherosclerotic disease and the rest had multiple cardiovascular risk factors. Just over half had diabetes and a third had prediabetes. All patients had a BMI of at least 27 kg/m2, with the median being 35 kg/m2.
During the first year of treatment, average weight fell by 4.2 kg in the lorcaserin group versus 1.4 kg in the placebo group, to give a significant 2.8 kg difference. At 1 year, patients taking lorcaserin had slightly lower levels of triglycerides and non-high-density lipoprotein cholesterol and their glycated hemoglobin level was 0.2% lower (0.3% among patients with diabetes at baseline). In addition, the annual rate of new-onset diabetes was significantly lower in the lorcaserin than placebo groups, at 3.1% versus 3.8%.
These findings are “consistent with an overall picture of an improved metabolic profile,” say the researchers, also noting that blood pressure and heart rate were slightly lower among patients taking lorcaserin versus placebo.
“In contrast, most other weight-loss agents cause an increase in heart rate and, in some instances, blood pressure,” they say.
Of adverse events possibly related to lorcaserin and leading to discontinuation, only headache and nausea were significantly more common than in the placebo group and these occurred in less than 1% of patients. Severe hypoglycemia with serious complications (hospitalization or life-threatening/disabling) occurred in significantly more patients in the lorcaserin than placebo group (0.22 vs 0.07%), with almost all cases occurring in patients who were taking insulin or sulfonylureas.
In an echocardiographic substudy involving 3270 patients, lorcaserin was associated with slight increases in the rates of valvulopathy and pulmonary hypertension. The researchers stress that the event rates were very low, however, precluding a significant difference.
NEJM deputy editor Julie Ingelfinger (Mass General Hospital for Children at Massachusetts General Hospital, Boston, USA) and Clifford Rosen (Tufts University School of Medicine, Boston) highlight these findings in an accompanying editorial, stressing 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 suggest that, for the time being, lorcaserin “may be best used on a cautious basis according to the needs of individual patients.” But they say it is “uncertain” whether the trial findings will boost the use of lorcaserin in clinical practice, considering that liraglutide “would provide a similar degree of weight loss but a lower risk of diabetes.”
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