Association of Changes in Glycemic- and Lipid-Related Cardiometabolic Risk Factors and Weight  Loss  in Pooled Lorcaserin Phase 3 Studies of Obese and Overweight Patients Without Diabetes (BLOOM and BLOSSOM)

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 660-676-Clinical Obesity Treatment
Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-665
Louis J. Arrone*1, William Shanahan2, Randi Fain3, Joanne Quan2, Wen Yu3, Tony Ma3 and Steven R Smith4
1Weill Cornell Medical College, New York, NY, 2Arena Pharmaceuticals, San Diego, CA, 3Eisai, Woodcliff Lake, NJ, 4Florida Hospital, Orlando, FL
Background

Lorcaserin (LOR), a selective 5-HT2C agonist, was approved by the FDA in 2012 as an adjunct to diet and exercise (DE) for chronic weight management in adults who are obese or overweight with at least 1 weight-related comorbidity. Obesity is a major risk factor for various comorbidities, especially diabetes and cardiovascular diseases, and weight reduction leads to significant improvements in cardiometabolic risk.

Objective

We determined the association between week 52 changes in cardiometabolic risk and weight loss from 2 randomized, placebo (PBO)-controlled studies in patients (pts) without diabetes who received LOR 10 mg BID or PBO with DE.

Methods/Results

The pooled PBO+DE (n=3185) and LOR+DE (n=3195) groups were comparable with respect to age (median 44.0 y and 44.0 y, respectively), BMI (35.6 kg/m2 and 35.8 kg/m2), weight (98.7 kg and 99.0 kg), sex (81.0% and 81.7% female) and racial composition. Age ranged from 18 to 66 y. The pooled LOR group had greater weight loss than the pooled PBO group at week 52 (5.76 kg vs 2.51 kg, P<0.001) in the modified intent-to-treat population with last observation carried forward (MITT/LOCF) and was confirmed by a repeated-measures analysis (P<0.0001) in MITT with nonmissing data. Lipid parameters (MITT/LOCF) were significantly decreased at week 52 in pooled LOR+DE compared with PBO+DE for triglycerides (LS mean % change from baseline, -5.30% vs -0.45%, respectively, P<0.001) and total cholesterol (-0.85% vs +0.37%, P<0.001), while LDL-C increased significantly less in LOR+DE vs PBO+DE (+1.62% vs +2.92%, P<0.015). The pooled LOR group had larger decreases in glucose parameters at week 52 than the PBO group, including fasting glucose (-0.23 mg/dL vs +0.60 mg/dL, P<0.001) and HbA1C (-0.12% vs -0.05%, P<0.001). To evaluate the correlation between weight change and glycemic parameters, weight change data by treatment group were sorted from lowest to highest and divided into deciles. Regression analysis based on those deciles in both LOR and PBO groups showed mean weight change was correlated to the mean change in the relevant parameter. For any given amount of weight loss, pts treated with LOR+DE showed a greater decrease in HbA1C from baseline than pts treated with PBO+DE.

 

Conclusions

These pooled data are in agreement with the results from the individual BLOOM and BLOSSOM trials, each of which showed that LOR+DE was associated with significant weight loss and improvements in cardiometabolic parameters compared with PBO+DE. Correlation analyses suggest that across the spectrum of weight loss, on average, pts treated with LOR+DE experience greater improvements in glycemic variables than those treated with PBO+DE.

Disclosure: LJA: Consultant, GlaxoSmithKline, Researcher, GI Dynamics, Consultant, Ethicon Endo-Surgery Inc, Researcher, Medical University of South Carolina (MUSC), Researcher, Aspire Bariatrics, Researcher, High Point Pharmaceuticals LLC, Researcher, GI Dynamics, Researcher, Medical University of South Carolina (MUSC), Consultant, Novo Nordisk, Researcher, High Point Pharmaceuticals LLC, Consultant, Amylin Pharmaceuticals, Consultant, Novo Nordisk, Consultant, Amylin Pharmaceuticals, Consultant, Orexigen Therapeutics Inc, Researcher, Aspire Bariatrics, Consultant, Vivus USA, Consultant, Ethicon Endo-Surgery Inc, Consultant, Takeda, Consultant, Zafgen Inc, Consultant, GlaxoSmithKline, , Cardiometabolic Support Network, LLC, Consultant, Orexigen Therapeutics Inc, Consultant, Vivus USA, , MYOS Corporation , Consultant, Takeda, , Zafgen Inc., Consultant, Zafgen Inc, Board Member, MYOS Corporation, , Cardiometabolic Support Network, LLC, , MYOS Corporation , , Zafgen Inc., Board Member, MYOS Corporation. WS: Consultant, Arena Pharmaceuticals. RF: Employee, Eisai. JQ: Consultant, Arena Pharmaceuticals. WY: Employee, Eisai. TM: Employee, Eisai. SRS: Consultant, Zafgen, Consultant, Takeda, Consultant, Piramal Life Sciences, Consultant, Orexigen Therapeutics, Inc. , Consultant, Novo Nordisk, Consultant, NGM Pharma, Consultant, Eli Lilly & Company, Consultant, Five Prime Therapeutics, Inc. , Consultant, Elcelyx, Consultant, Bristol-Myers Squibb, Consultant, Astra Zeneca, Consultant, Arena Pharmaceuticals, Consultant, Amylin Pharmaceuticals, Advisory Group Member, Takeda, Advisory Group Member, Amylin Pharmaceuticals.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm