Lorcaserin (trade name Belviq) is an obesity medication that is not available in Canada, but is used in USA and other countries as a treatment of obesity. A recent study evaluated the cardiovascular safety of lorcaserin in people with obesity or overweight, with either established cardiovascular (CV) disease, or multiple cardiovascular risk factors but without established CV disease. (skip to BOTTOM LINE below as to why this study is important)
In the study, published in the New England Journal of Medicine, 12,000 people were randomized to receive either lorcaserin or placebo for a median of 3.3 years. Seventy-five percent of participants had established cardiovascular disease. At one year, people on lorcaserin lost -4.2kg, compared to -1.4kg in the placebo group. At 3.3 years, there was no difference in the rate of cardiovascular events (a composite of cardiovascular death + nonfatal heart attack + nonfatal stroke) between groups, at 2.0% per year on lorcaserin vs 2.1% per year on placebo.
In people who had diabetes at the start of the study (57% of the total population), diabetes control was improved slightly at 1 year (-0.3% greater reduction in A1C than placebo). Amongst those with prediabetes at the start, the proportion of people on lorcaserin who went on to develop type 2 diabetes was slightly lower (3.1% per year) than those on placebo (3.8% per year).
The rate of discontinuation of study medication was similar between the two groups, at 12.0% per year in the lorcaserin group vs 12.7% in the placebo group. In the lorcaserin group, the most common side effects leading to stopping treatment were known potential side effects of dizziness, fatigue, headache, diarrhea, and nausea.
Echocardiogram (heart ultrasound) was performed in a subset of 3270 study participants, because an related obesity medication previously available (fentermine-phenfluramine or Fen-Phen) was found to have an adverse effect on heart valves. After a year of treatment, they found no statistically significant difference in heart valve problems between the two groups, with 23 cases of new onset, mild aortic valve insufficiency on lorcaserin vs 15 on placebo, and 13 cases of pulmonary hypertension on lorcaserin vs 8 on placebo.
So what’s the BOTTOM LINE? This is the first time that the cardiovascular safety of an obesity medication has been rigorously tested and proven to be safe. Some previously available obesity medications have been pulled from most markets due to safety concerns (eg sibutramine due to increased cardiovascular events in people with CV disease, rimonabant due to psychiatric side effects).
Regarding the three currently available obesity medications in Canada:
- Orlistat (Xenical) has not been tested in this fashion
- Liraglutide as a diabetes treatment (Victoza 1.8mg) has been shown to reduce cardiovascular events and death in people with type 2 diabetes. Though liraglutide as an obesity treatment (Saxenda 3.0mg) has not been specifically studied for CV safety, these data are accepted by regulatory agencies as reassurance for CV safety in the lower risk population of people with obesity without diabetes
- Naltrexone/bupropion (Contrave) had a study started but stopped part way through because of a release of interim results that was felt to compromise the integrity of the study. A new trial is now in the planning stages.
Looking very forward to more safety outcome data in this area.
Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the makers of liraglutide (Novo Nordisk) and naltrexone/bupropion (Valeant).