Lorcaserin, a Selective 5-HT2C Agonist, Is Efficacious for Weight Loss across Patient Subgroups
Abstract Number: 1845-P
Authors: CHRISTEN M. ANDERSON, MATILDE SANCHEZ, JACEK KROLIKOWSKI, MARIANNE MANCINI, WILLIAM R. SHANAHAN
Institutions: San Diego, CA
Results: Lorcaserin is a selective agonist of the 5-HT2C receptor that caused significant weight loss in phase 3 clinical trials. Post-hoc analyses of subgroups from these trials were conducted to determine whether demographic characteristics predict responsiveness to lorcaserin (L).
Two randomized, placebo (P) controlled studies evaluated L in obese or overweight patients; 3185 took P and 3195 took L 10 mg BID. In the overall population, L caused 5.8% weight loss from baseline at Week 52, compared to 2.5% with P (p<0.0001; ITT/LOCF). Weight loss was similar in men and women (5.3% and 5.9% L, 2.8% and 2.4% P). On average, Caucasian (C) patients lost more weight (6.7% L, 3.0% P) than did African American (AA) patients (4.0% L, 1.2% P) or Hispanic (H) patients (3.7% L, 1.6% P), and patients older than 50 lost more weight (7.9% L, 3.5% P) than did younger patients (4.8% L, 2.0% P). Demographic trends were similar in the L and P groups. L plasma concentrations were comparable among the racial, gender and age subgroups on a population basis; hence, L exposures do not explain the differing weight loss among the L subgroups.
L caused significant improvements in serum lipids, fasting glucose and blood pressure in the overall population; trends similar to the overall population were seen in all subgroups evaluated. Gender did not significantly affect difference in means (L vs. P) for change from baseline in cholesterol (-1.7% men, -1.1% women) or LDL (-2.1% men, -1.2% women). Age had no effect on difference in means for change in cholesterol (-1.5% over 50, -1.0% 50 or younger) or LDL (-2.2% >50, -1.0% ≤ 50). Race did not affect L vs. P for change in cholesterol (-1.5% C, 0.1% AA, -1.2% H), LDL (-1.6% C, -1.5% AA, 0.1% H), HDL (1.5% C, 0.6% AA, 0.5% H), or glucose (-0.7% C, -1.3% AA, 0.0% H). Triglycerides, HDL and glucose improved in men and women, and in patients >50 and ≤50; however, significantly greater improvements were observed in men and in patients >50.
Lorcaserin promoted weight loss compared to placebo in all subgroups examined, and improved the majority of secondary endpoints as compared to placebo in each subgroup.