Congress Reports

MedWire - ADA (New Orleans, LA, USA), June 8, 2009: Treatment with lorcaserin enabled patients with type 2 diabetes to lose more body weight than with a strategy of behavioral modification alone, according to findings from the Behavioral modification and Lorcaserin for Overweight and Obesity Management (BLOOM) trial. Lorcaserin also provided favorable changes in lipids and other metabolic outcomes without increasing cardiotoxicity.

Lorcaserin is a selective 5-hydroxytryptamine 2C (5-HT2C) receptor agonist that stimulates the serotonin receptor, an important modulator of food intake. The BLOOM trial was designed to evaluate whether treatment with lorcaserin could enhance weight reduction in patients treated with behavioral modification counseling, a modest exercise program, and a low-calorie diet.

The findings of BLOOM were presented as a late-breaking abstract on the fourth day of the Annual Meeting of the American Diabetes Association (ADA) 2009.

BLOOM study design
Dr. Steven R. Smith, Pennington Biomedical Research Center, Baton Rouge, LA, USA

The BLOOM trial included 3182 patients with type 2 diabetes, a mean body weight of 100 kg, and a mean body mass index of 36.2 kg/m². The mean age of trial participants was 44.1 years, and 83.5% of the patients were women.

Patients were randomly assigned to receive treatment with lorcaserin 10 mg twice-daily (n=1595) or placebo (n=1587) for the first year of the trial. All patients also received behavioral modification counseling, participated in a modest exercise program, and followed a 600 kcal-deficient diet. At the end of the first year, patients in the lorcaserin group were randomly assigned to either continue treatment with lorcaserin or start receiving placebo, whereas patients who were initially in the placebo arm remained on placebo for the second year of the study.

The primary endpoints were as follows:

• the percent of patients losing ≥ 5% of their baseline body weight by 52 weeks
• the mean weight change at 52 weeks
• the percentage of patients losing ≥ 10% of their baseline body weight by 52 weeks
• among those participants who remained in the trial during the second year, the percentage of patients who maintained ≥ 5% weight loss at week 104

For the safety analysis, echocardiograms were performed at screening and at months 6, 12, 18 and 24.

By the end of the first year, 55.4% of patients in the lorcaserin group and 45.1% of those in the placebo group remained in the study. Of those who underwent the second randomization, 74.3% of patients in the lorcaserin arm and 72.7% of patients in the placebo arm completed the second year..

Weight reduction with lorcaserin
Treatment with lorcaserin led to a significantly greater weight reduction than placebo for all of the endpoint measures. At 52 weeks, 47.5% of patients in the lorcaserin group and 20.3% in the placebo group lost ≥ 5% of baseline body weight (p<0.0001). This included 22.6% of patients in the lorcaserin group and 7.7% in the placebo group who lost ≥ 10% of their baseline body weight (p<0.0001).

The mean weight loss at 52 weeks was 5.8 kg in the lorcaserin group and 2.2 kg in the placebo group (p<0.0001) in an intent-to-treat analysis. According to a per-protocol analysis that evaluated only those patients who were compliant with treatment, the mean weight loss at 52 weeks was 8.2 kg and 3.4 kg in the lorcaserin and placebo groups, respectively (p<0.0001).

Among patients who remained in the study during the second year, those who remained on lorcaserin experienced less weight regain than those who were re-randomized to receive placebo.

Metabolic and safety outcomes
Treatment with lorcaserin also had a beneficial effect on lipid profile and other metabolic outcomes. By 52 weeks, total cholesterol decreased by 3.2 mg/dL in the lorcaserin group and by 0.3 mg/dL in the placebo group (p=0.0002). A large part of this change was driven by a reduction in triglyceride levels. In the lorcaserin group, the triglyceride levels were reduced by19.0 mg/dL, and in the placebo group they were reduced by 9.2 mg/dL (p<0.0001).

Patients in both groups saw an increase in low-density lipoprotein (LDL) levels, although the increase was less pronounced in the lorcaserin group than it was in the placebo group (+2.8 mg/dL vs. +4.0 mg/dL, respectively; p=0.04). Changes in high-density lipoprotein (HDL) were not significantly different between the lorcaserin and placebo groups (+0.05 mg/dL vs. -0.21 mg/dL, respectively; p=0.71).

Lorcaserin was also associated with a greater reduction in baseline systolic blood pressure (-1.4 mm Hg vs. -0.8 mm Hg; p=0.03) and baseline diastolic blood pressure (-1.1 mm Hg vs. -0.6 mm Hg; p=0.01) in comparison with placebo. Patients in the lorcaserin group also benefited from more favorable changes in heart rate than those patients in the placebo group (-2.0 bpm vs. -1.6 bmp; p=0.04). In comparison with the placebo group, patients in the lorcaserin group also showed improved fasting glucose levels (-0.8 mg/dL vs. +1.1 mg/dL; p<0.0001), fasting insulin levels (-3.3 µ IU/mL vs. -1.28 µ IU/mL; p=0.0002), and high-sensitivity C-reactive protein (hsCRP) levels (-1.378 mg/L vs. -0.075 mg/L; p<0.0001).

The safety analysis showed no difference in the proportion of patients in the lorcaserin and placebo groups that developed valvulopathy at any time point, including week 24 (2.1% vs. 1.9%; p=0.88), week 52 (2.7% vs. 2.3%; p=0.70), or week 104 (2.6% vs. 2.7%; p=1.0).

Lorcaserin was well tolerated. The most frequent adverse events in the lorcaserin group were headache (18%), upper respiratory infection (14.8%), and nasopharyngitis (13.4%). Lorcaserin was not associated with an increase in depression or suicidal ideation compared with placebo. A similar proportion of patients in the lorcaserin and placebo groups reported any serious adverse events during the first year (2.4% vs. 2.3%) and the second year (2.6% vs. 2.1%).

In summary, lorcaserin is a promising investigational agent in the treatment of obesity in patients with type 2 diabetes. In addition to providing greater weight reduction than placebo, lorcaserin also improved other aspects of the cardiovascular risk profile, such as lipid levels, heart rate, and hsCRP levels, without increasing cardiotoxicity.