Treatment Demonstrated Sustained Weight Loss

San Francisco—The Centers for Disease Control and Prevention estimate that 69% of adults ≥20 years of age are overweight or obese, which puts patients at an increased risk of obesity-related comorbidities, such as diabetes, cardiovascular disease, osteoarthritis, and cancer. A product theater presented at the ADA meeting by Farhad Zangeneh, MD, FACP, FACE, medical director, Endocrine Diabetes and Osteoporosis Clinic, Sterling, Virginia, provided an overview of the disease state as well as data on a pharmacotherapeutic treatment option. This product theater was sponsored by Eisai Co., Ltd.

“The ramifications of obesity warrant a paradigm shift in the way the medical community tackles this complex disease,” said Dr. Zangeneh, noting that the American Medical Association officially recognized obesity as a disease in 2013. “Obesity meets all the criteria for a medical disease.”

Obesity is multifactional, encompassing behavior, physiology, and genetics. When deciding on a weight loss treatment in obese or overweight patients, physicians should consider the patient’s motivation to make the necessary lifestyle changes. The American Association of Clinical Endocrinologists’ algorithm, published by Garber et al in Endocrine Practice in 2013, supports the use of pharmacotherapy in conjunction with lifestyle modifications as initial treatment options for patients with a body mass index (BMI) ≥27 kg/m² who also have comorbidities. Pharmacotherapy options outlined in the algorithm included lorcaserin hydrochloride (HCl). Lorcaserin HCl is a serotonin 2C receptor agonist indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI ≥30 kg/m² or a BMI ≥27 kg/m² in the presence of at least 1 weight-related comorbidity. Although the exact mechanism of action is unknown, Dr. Zangeneh said lorcaserin HCl is believed to promote satiety by mimicking serotonin activity in the hypothalamus.

The safety and efficacy of lorcaserin HCl was evaluated in 3 phase 3 studies: BLOOM [Behavioral Modification and Lorcaserin for Obesity and Overweight Management], BLOSSOM [Behavioral Modification and Lorcaserin Second Study for Obesity Management], and BLOOM-DM [Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus]. All studies were randomized, double-blind, placebo-controlled trials ranging from 52 weeks to 104 weeks. The primary end point in these studies was weight loss at 1 year, which was assessed by the percentage of patients achieving ≥5% weight loss, the percentage of patients achieving ≥10% weight loss, and mean weight change. BLOOM and BLOSSOM included patients without type 2 diabetes with a BMI of
30 kg/m² to 45 kg/m² or 27 kg/m² to 29.9 kg/m² with at least 1 comorbidity. BLOOM-DM included patients with uncontrolled type 2 diabetes being treated with metformin and/or a sulfonylurea and a BMI of ≥27 kg/m². In the pooled BLOOM and BLOSSOM 1-year trial results, lorcaserin HCl was found to help more patients in the modified intent-to-treat (MITT) population meet the primary end point versus placebo.

At 52 weeks, the mean weight loss was 5.8% with lorcaserin HCl versus 2.5% with placebo. The percentage of patients losing ≥5% and ≥10% of body weight was greater with lorcaserin HCl versus placebo (47.1% and 22.4% vs 22.6% and 8.7%, respectively). Furthermore, 2-year data from BLOOM showed that patients who continued with lorcaserin HCl maintained ≥5% weight loss compared to patients who switched to placebo (67.9% vs 50.3%, respectively).

Results from BLOOM-DM also showed that more patients randomized to receive lorcaserin HCl met the primary end point compared with placebo. At 52 weeks, the mean weight loss was 4.5% with lorcaserin HCl compared to 1.5% with placebo.

The study also looked at the effect of lorcaserin HCl on various cardiometabolic parameters, including hemoglobin A1c (HbA1c). The study found that patients in the lorcaserin HCl group demonstrated significant improvement in HbA1c compared with placebo (mean change from baseline -0.9% vs -0.4%, respectively).

The most common adverse reactions with lorcaserin HCl among patients without diabetes were headache (17%), dizziness (9%), fatigue (7%), nausea (8%), dry mouth (5%), and constipation (6%). Among patients with diabetes, adverse reactions included hypoglycemia (29%), headache (15%), back pain (12%), cough (8%), and fatigue (7%).

The recommended dose of lorcaserin HCl is 10 mg administered orally twice daily. Physicians should evaluate response to therapy by week 12. If a patient has not lost ≥5% of baseline body weight, discontinue lorcaserin HCl, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.—Eileen Koutnik-Fotopoulos