Early weight loss while on lorcaserin, diet and exercise as a predictor of week 52 weight‐loss outcomes

Abstract

Objective: To identify an early treatment milestone that optimizes sensitivity and specificity for predicting 5% weight loss at Week (W) 52 in patients with and without type 2 diabetes on lorcaserin or placebo. Methods: Post hoc area under the curve for receiver operating characteristic analyses of data from three phase 3 trials comparing lifestyle modification1placebo with lifestyle modification1lorcaserin. A total of 6897 patients (18-65 years; BMI, 30-45 or 27-29.9 kg/m 2 with 1 comorbidity) were randomized to placebo or lorcaserin 10 mg bid. Changes (baseline to W52) in cardiometabolic parameters were assessed. Results: Response (5% weight loss from baseline) at W12 was a strong predictor of W52 response. Lorcaserin patients with a W12 response achieved mean W52 weight losses of 10.6 kg (without diabetes) and 9.3 kg (with diabetes). Proportions achieving 5% and 10% weight loss at W52 were 85.5% and 49.8% (without diabetes), and 70.5% and 35.9% (with diabetes). Lorcaserin patients who did not achieve a W12 response lost 3.2 kg (without diabetes) and 2.8 kg (with diabetes) at W52. Responders had greater improvements in cardiometabolic risk factors than the modified intent-to-treat (MITT) population, consistent with greater weight loss. Conclusions: 5% weight loss by W12 predicts robust response to lorcaserin at 1 year.

Longitudinal Weight Loss Patterns and their Behavioral and Demographic Associations

“…(profiles 2 and 3) compared profile 1. This observation is in agreement with numerous reports suggesting an association between greater initial weight loss and long-term success in response to both behavioral interventions alone (5, 9, 12, 14, 59–64) or when behavioral interventions are combined with weight loss medications (65, 66). For example, results from the Look AHEAD trial indicated weight loss at 1-year was a strong determinant of 4-year weight loss (61).…”

“…In a primary care based translation of the DPP lifestyle intervention Yank et al (4) reported that only participants who lost ≥ 5% of baseline weight at 3 months were able to maintain this weight loss at 15 months. Smith et al (66) combined data from 3 separate phase 3 trials of lifestyle modification plus Locaserin (n= 6897) in adults. Results indicated that weight loss > 5% at week 12 was a strong predictor of weight loss at 1 year in adults with and without type 2 diabetes.…”

Lorcaserin Administration Decreases Activation of Brain Centers in Response to Food Cues and These Emotion- and Salience-Related Changes Correlate With Weight Loss Effects: A 4-Week-Long Randomized, Placebo-Controlled, Double-Blind Clinical Trial

“…Indeed, studies have shown that weight loss by week 12 with lorcaserin is a strong predictor of longer-term (52 weeks) success (47), which may indicate a good time at which to determine individual differences in response to lorcaserin. Overall, these results are strong and indicate clear changes in brain responses to food cues with lorcaserin therapy.…”

New Medications for Treatment of Obesity: Metabolic and Cardiovascular Effects

“…10% weight loss of 85.5% and 49.8% (without T2D), and 70.5% and 35.9% (with T2D). 43 CM effects. A meta-analysis on secondary outcomes showed that compared with placebo, lorcaserin decreased mean waist circumference by 2.51 cm, systolic BP (SBP) by 0.61 mm Hg, diastolic BP (DBP) by 0.49 mm Hg, with no significant difference in heart rate (HR).…”

“…However, increasingly in evaluating efficacy of drugs, responder populations can be defined early and may serve to limit exposure of nonresponsive patients to drug and selectively enhance outcomes. 43 Regulatory authorities increasingly require a weight loss threshold for continued medication as part of the product license.…”