Health‐related quality of life in randomized controlled trials of lorcaserin for obesity management: what mediates improvement?

Abstract

Lorcaserin, plus diet and exercise, has demonstrated significant weight loss and improved cardiometabolic parameters vs. placebo in patients with overweight/obesity in three randomized, placebo-controlled trials. We examined whether lorcaserin is also associated with greater improvements in health-related quality of life (HRQOL) and whether these improvements are wholly attributable to weight loss. Pooled data from Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM), Behavioral Modification and Lorcaserin Second Study for Obesity Management (BLOSSOM) and BLOOM-Diabetes Mellitus (BLOOM-DM) trials were analysed (n = 5624). HRQOL was assessed at baseline and 52 weeks using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire. Multiple mediation analyses were conducted to evaluate the mechanisms underlying improved HRQOL. Greater HRQOL improvements were observed at 52 weeks in lorcaserin vs. placebo (P < 0.0001). A greater percentage of lorcaserin patients (54.1%) experienced meaningful improvements in IWQOL-Lite total score than placebo patients (48.2%) (P < 0.001). Body mass index (BMI) reduction was the primary driver of improved HRQOL (P < 0.0001), with depressive symptoms and total cholesterol also playing a role (P < 0.05). Improved HRQOL varied by gender, age, race and presence of diabetes and other comorbidities. Lorcaserin treatment significantly improves HRQOL compared with placebo. Although BMI reduction accounts for the majority of these improvements, improvement in depressive symptoms and total cholesterol are contributing factors.

Chronic Lorcaserin Treatment Reverses the Nicotine Withdrawal-Induced Disruptions to Behavior and Maturation in Developing Neurons in the Hippocampus of Rats

“…Our results obtained in drug-weaned rats are in concordance with our previous observations showing that acute treatment with other 5-HT 2C receptor agonists (Ro60-0175, WAY163,909) reduced the increased immobility time in rats withdrawn from passive nicotine [27]. The findings support clinical studies that show an improvement in depression symptoms in patients given lorcaserin to treat obesity [48], although one case report showed the development of depressive symptoms after lorcaserin treatment [49]. Thus, our data indicate that chronic lorcaserin administration, only at a subthreshold dose, attenuated the depression-like phenotype observed during nicotine withdrawal.…”

Improvement in mood symptoms ​after post‐bariatric surgery among people with obesity: A systematic review and meta‐analysis

“…Lorcaserin, a selective serotonin (5HT 2C ) receptor agonist, used as an adjunct to diet and exercise, can significantly reduce body weight in people with either overweight or obesity 48–51 . In addition to cardiometabolic benefits, patients have reported improvements in HRQOL, which was mediated by BMI reduction and improvement of depressive symptoms 51,52 . Due to reports of increased incidence of cancer, lorcaserin has since been withdrawn by the United States Food and Drug Administration (US FDA).…”

Centrally Acting Agents for Obesity: Past, Present, and Future

“…It also slowed the progression of prediabetes to diabetes and increased the percentage of subjects with prediabetes that reverted to euglycemia, a finding that is associated with a longer prevention of diabetes[82]. Analysis of the three phase 3 clinical trials demonstrated a significant improvement in health related quality of life and depression measured by the Impact of Weight on Quality of Life-Lite questionnaire mostly attributable to weight loss[83]. Analysis of the three phase 3 trials also demonstrated a 2.04% incidence of new cardiac valvulopathy in the placebo group and 2.37% in the lorcaserin group giving a risk 1.15 for those attaining a 5% weight loss[84].…”