- This study aims to assess the heart safety of lorcaserin, a weight management drug in obese or overweight patients who have established heart disease or other risk factors of heart disease such as high blood sugar, hypertension and increased lipids
- Many earlier weight loss agents have caused serious heart and psychiatric complications leading to their withdrawal from the market. Currently there is need for a safe weight loss drug
- Being overweight or obese is associated with several complications including heart disease; weight loss drugs are recommended in some patients in addition to lifestyle changes for sustained longterm health benefit and reduction of these risks
Lorcaserin, a weight loss agent is known to be effective in overweight and obese patients. The current multinational clinical trial aims to assess the safety of lorcaserin in overweight or obese patients with established heart disease or having risk factors of heart disease. The trial termed "CAMELLIA-TIMI 61 (Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients-Thrombolysis in Myocardial Infarction 61)", was carried out in 473 centers across eight countries.
The findings of the study titled "Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients" is published in the New England Journal of Medicine.
Testing Heart Safety of Lorcaserin Versus Placebo
- Obese or overweight patients numbering 12,000 were randomly assigned to receive either lorcaserin 10 mg twice daily or placebo
- The average age of the participants was 64 years, and the median body mass index (BMI) was 35. The trial had 64.2 percent male participants. The patients were followed up for an average duration of 3.3 years
- Participants had a wide range of coexisting risk factors of heart disease, such as hypertension (90.4%), diabetes (56.8%), hyperlipidemia (93.6%), and chronic kidney disease (19.0%). About 8958 patients (74.7%) had narrowing of coronary arteries that supply blood to the heart due to build-up of fatty material in the vessel wall (atherosclerotic heart disease)
- During follow-up at one year, a minimum 5% weight loss was noted in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) persons in the group assigned to placebo.
- Throughout the 40 month follow-up period, the lorcaserin group showed a significantly higher degree of weight loss compared to the placebo group
- At the same time (one year follow-up), patients in the lorcaserin group showed slightly better parameters with regards to heart disease risk factors (including blood sugar, blood pressure, heart rate and lipids) compared to the placebo group
- The rate of occurrence of major heart related events (including death, heart attack, or stroke) assessed in the interim follow-up period was 2% per year in the lorcaserin group and 2.1% per year in the placebo group
- Similarly the occurrence of serious heart events at the end of the trial period (3.3 years) was 4.1% per year and 4.2% per year in the lorcaserin and placebo groups respectively
- Other adverse effects were uncommon, and the rates were generally identical in the two groups, except for the lorcaserin group showing a higher incidence of patients with serious hypoglycemia (low blood sugar)
Safety Profile of Lorcaserin Versus Earlier Weight Loss DrugsLorcaserin belongs to the group of drugs termed selective serotonin receptor agonist, and regulates appetite by stimulating the area in the brain which makes a person feel full and reduces appetite. Based on results in weight-loss trials, lorcaserin was approved by the Food and Drug Administration (FDA) as an adjunct to lifestyle changes such as low calorie diet and increased physical activity to help with long term weight loss.
Following harmful occurrences such as the above, the FDA has now approved weight-loss agents subject to the condition that post market safety clinical trials can prove that these agents do not cause a higher rate of adverse heart related effects.
Benefits of Various Weight Loss Strategies In Reducing Adverse Heart Related Events
The various weight loss strategies include lifestyle modifications, medications and bariatric or weight loss surgery.
- Interestingly, none of the specific lifestyle modifications or medications (including lorcaserin) used as weight-loss strategy that have been studied so far have shown a reduction in cardiovascular events
- Lorcaserin is found to promote sustained weight loss without a higher rate (but not significant reduction) of occurrence of adverse heart events compared to placebo
- It is thus possible that weight loss alone does not influence risk of major adverse heart related events or it is possible that the slight weight reductions typically seen with medications or lifestyle measures must be sustained over a prolonged period of time to actually reduce heart disease risk
- Observational studies of bariatric surgery (which offer a higher rate of sustained weight loss than pharmacologic or lifestyle-modification strategies), have shown a reduction of adverse heart related events including death, heart attack, stroke, and heart failure over a follow-up period of 10 to 20 years
- However, randomized trials (which are considered the gold standard) of bariatric surgery conducted so far have not demonstrated the statistical power needed to measure the association between bariatric surgery and reduction in adverse heart events
- Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients - (https://www.nejm.org/doi/full/10.1056/NEJMoa1808721)