Lorcaserin and Cardiovascular Outcomes
Oct 16, 2018, 17:06 PM
Within and outside of clinical practice, I love discussing obesity management. Since June 2012, there have been four drugs approved by the Food and Drug Administration for long-term weight management. These medications include lorcaserin (marketed as Belviq), phentermine with topiramate (marketed as Qsymia), bupropion with naltrexone (marketed as Contrave), and liraglutide (marketed as Saxenda). Each medication has advantages and disadvantages. For example, Qsymia is the most effective agent for weight loss but consists of two medications, which can mean more contraindications and drug-drug interactions. As another example, Saxenda is the only injectable medication, which presents a barrier for people with a fear of needles. We must always look at patient-specific factors before deciding to prescribe or recommend one of these particular medications for long-term weight loss.
Among these agents there are randomized, placebo-controlled trials investigating their efficacy and safety among certain patient populations. Most often, the patient populations were those with metabolic syndrome or diabetes and the primary outcome was weight loss over a specific period of time. The most common period was one to two years, but Saxenda has evidence over three years. These medications were compared to a placebo to find statistically significant differences, such as more than 5% weight loss from baseline in comparison to the placebo group or more than 35% of patients in the treatment group achieving a 5% weight loss. These outcomes are considered statistically significant as evidence-based guidelines recommend a 5 to 10% weight loss in order to improve metabolic endpoints.
In late August 2018, a paper titled “Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients” was published in the New England Journal of Medicine. The authors wanted to determine the efficacy and safety of this specific agent among patients who were overweight or had obesity but had also a significant cardiovascular history or risk factors for cardiovascular disease. The randomized, double-blind and placebo-controlled study investigated major cardiovascular events as a composite endpoint. The composite endpoint consisted of death from cardiovascular event, myocardial infarction or stroke.
Time will tell how this evidence impacts clinical practice and possibly how these anti-obesity medications are covered by insurance.
First, the patient population was older (average: 64 years of age) and consisted of more male patients (65%, compared to 70-80% female in other trials). In addition, 25% of the patients had risk factors for cardiovascular disease, compared to 75% having baseline cardiovascular disease. Lastly, medications are important to note at baseline, as 75%, 75%, and 85% were taking aspirin, an ACE-inhibitor (or ARB), and statins, respectively. For the results, lorcaserin 10 mg orally twice daily did not cause or prevent major cardiovascular events at the interim analysis or at the completion of the trial. The only statistically significant finding was new-onset diabetes, meaning lorcaserin had fewer cases compared to the placebo arm (8.5% versus 10.3% out of 6000 patients in each arm); however, this finding was a secondary outcome.
While the results of this trial were neutral for lorcaserin, it is still evidence that we did not have before. As with antidiabetic agents, the anti-obesity agents will have cardiovascular data over the next few years. This information will provide more detail for choosing one specific agent over another. So, time will tell how this evidence impacts clinical practice and possibly how these anti-obesity medications are covered by insurance.
What are your thoughts? Share in the comments a time that you may have recommended or talked to a patient about one of these anti-obesity medications.
About the Author
Jennifer Clements received her Doctorate of Pharmacy from Campbell University in 2006 and completed a primary care residency at a Veterans Affairs Medical Center in 2007. She is also a certified diabetes educator and board certified in pharmacotherapy. Currently, she is an Associate Professor of Pharmacy Practice at Presbyterian College School of Pharmacy.