• Diabetes & Endocrinology Clinical Trials
• Obesity
• Diabetes Mellitus
• Nutrition Clinical Trials

• Diabetes & Endocrinology Clinical Trials
• Endocrinology
• Diabetes & Metabolic Syndrome
• Obesity
• Diabetes Mellitus
• Nutrition Clinical Trials

Elisa Fabbrini, MD, PhD, Washington University School of Medicine, St Louis, Missouri, USA, discussed a post hoc analysis of data from the phase 3 Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus study [BLOOM-DM; NCT00603291], concerning the effects of the weight loss drug lorcaserin in patients with type 2 diabetes mellitus (T2DM) who are overweight or obese.

About 85% of Americans with T2DM are overweight or obese [Centers for Disease Control and Prevention. Morb Mortal Wkly Rep. 2004]. Sustained weight reduction of 3% to 5% is advantageous in improving glycemic control [Jensen MD et al. Circulation. 2014; Wing RR et al. Diabet Care. 2011]. Lorcaserin is a selective 5-HT_2c receptor agonist that acts to decrease food consumption and promote satiety, and it has been approved for weight loss in conjunction with diet and exercise.

In the 52-week BLOOM-DM trial, obese and overweight T2DM patients were randomized 1:1:1 in a double-blind manner to placebo, lorcaserin-10 mg QD, or lorcaserin-10 mg BID, in conjunction with a calorie-reduced diet and exercise. Significant reductions versus placebo were evident in HbA_1c and fasting plasma glucose levels in patients receiving lorcaserin BID [O'Neil PM et al. Obesity. 2012].

The present post hoc analysis involved patients who were randomized to either placebo or lorcaserin BID, who received ≥ 1 dose of study drug, and whose post-baseline weight was measured at least once—that is, the modified intention-to-treat population. This retrospective analysis aimed to evaluate the putative weight-loss independent effects of lorcaserin on HbA_1c, fasting plasma glucose, and fasting plasma insulin.

The baseline characteristics of patients treated with placebo or lorcaserin BID were comparable (Table 1).

Patients receiving lorcaserin BID displayed significant reductions (P < .001) in fasting plasma glucose when compared with the placebo group, beginning at week 2 and continuing through to week 52. The drop in glucose levels preceded any significant weight loss. A similar pattern of glucose reduction was also evident among a subgroup of patients who did not lose weight while on lorcaserin treatment and who were therefore considered nonresponders (defined as weight loss ≥ 5% at 12 weeks).

Reductions in HbA_1c were significantly greater in the lorcaserin-treated group as compared with the placebo group starting at week 12 (first measurement of HbA_1c) throughout week 52. A similar pattern of reduction in HbA_1c was evident in the nonresponder group, even though no changes in body weight occurred. Mean changes in fasting plasma insulin from baseline were not significantly different in patients treated with lorcaserin BID and placebo.

Examination of 256 patients receiving lorcaserin BID and 252 receiving placebo revealed increased treatment-related adverse events of hypoglycemia (29.3% vs 21.0%), headache (14.5% vs 7.1%), back pain (11.7% vs 7.9%), cough (8.2% vs 4.4%), and fatigue (7.4% vs 4.0%).

These post hoc observations of a significant lorcaserin-mediated reduction in fasting plasma glucose and HbA_1c before or in the absence of significant weight loss suggest that lorcaserin might affect glucose homeostasis, at least in part, independently from weight loss. Further prospective randomized clinical trials are needed to confirm these observations.

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